Andrea Henry, PharmD, MBA, BCPS Specialty Drug Information Pharmacist
Katie Lockhart
Senior Manager, Forecasting and Pharmacoeconomics
Simone Ndujiuba, PharmD, BCOP Director, Clinical Strategy and Innovation, Oncology
Olivia Pane, PharmD, CDCES Drug Information Pharmacist
Nothing herein is or shall be construed as a promise or representation regarding past or future events and Magellan Rx Management expressly disclaims any and all liability relating to the use of or reliance on the information contained in this presentation. The information contained in this publication is intended for educational purposes only and should not be considered clinical, financial, or legal advice. By receipt of this publication, each recipient agrees that the information contained herein will be kept confidential and that the information will not be photocopied, reproduced, distributed to, or disclosed to others at any time without the prior written consent of Magellan Rx Management.
Editor-in-Chief's MESSAGE
Welcome to the MRx Pipeline. This quarterly publication offers clinical insights and competitive intelligence on anticipated drugs in development, so you are well-sourced on the drug pipeline.
MRx Pipeline, our universal forecast, addresses trends applicable across market segments. Traditional and specialty drugs as well as agents under the pharmacy and medical benefits are featured. Also profiled in the report are new molecular entities, pertinent new and expanded indications for existing medications, and biosimilars.
Clinical analyses, financial outlook, and pre-regulatory status are considered. The products housed in the MRx Pipeline have been researched in detail. They have been developed in consultation with our internal team of clinical and analytics experts.
METHODOLOGY
Emerging therapeutics continue to grow and influence the clinical and financial landscape. Therefore, Magellan Rx Management has developed a systematic approach to determine the products with significant clinical impact. For the in-depth clinical evaluations, the products’ potential to meet an underserved need in the market by becoming the new standard of care, and the ability to replace existing therapies were investigated. The extent to which the pipeline drugs could shift market share on a formulary and their impact on disease prevalence were also important considerations. In order to assist payers with assessing the potential impact of these pipeline drugs, where available, a financial forecast has been included for select products. Primarily complemented by data from EvaluateTM, this pipeline report looks ahead at the 5-year projected annual US sales through the year 2027. These figures are not specific to a particular commercial or government line of business; rather, they look at forecasted total US sales. Depending on a variety of factors, including the therapeutic categories, eventual FDA-approved indications, populations within the plan, and other indices, the financial impact could vary by different lines of business.
REFLECTION
Thus far in 2023, the agency has approved 13 novel drugs. Notably, most of the approvals so far in 2023 use at least one of the FDA’s expedited approval methos and the majority are designated as Orphan Drug. Some of the products include first-time approvals for rare diseases, a new agent for Alzheimer’s disease, new oncology drugs, a new option for the treatment of anemia caused by chronic kidney disease, among others.
While numbers do not tell the entire story, they do represent significant innovation in patient care and advance public health for the American public.
ON THE HORIZON
As we look ahead, and with the COVID-19 Public Health Emergency (PHE) ending on May 11, 2023, there is a continued trend towards the approval of specialty medications and drugs for rare conditions, with 65% and 33% of approvals expected, respectively, for agents with applications submitted to the FDA. There are 2 agents seeking FDA’s Accelerated Approval, which allows for earlier drug approval for serious conditions that fill an unmet need based on a surrogate endpoint reasonably likely to predict a clinical benefit. Approval of 2 new vaccines for RSV prophylaxis in older adults is expected with a biologic for younger ages on the horizon. Several injectable gene therapies are awaiting FDA decision for hemophilia A, sickle cell anemia and thalassemia, Duchenne muscular dystrophy, as well as a topical gene therapy for a rare dermatologic condition. Other noteworthy pipeline trends to watch include the development of complex therapies, cell therapies, oncology, immunology, immunotherapy, and therapeutic options for ultra-rare hereditary diseases. The launch of several Humira® biosimilars is anticipated to in July 2023. Moreover, sprouting products for obesity and women’s health are being actively monitored through MRx Pipeline
The drug pipeline ecosphere will continue to evolve as it faces challenges and successes. Innovative agents that show positive results without compromising patient safety and access offer true therapeutic advances and hold the promise to alter the treatment paradigm.
Objective evidence-based methodology was used to identify the Deep Dive drugs in the upcoming quarters. This section features a clinical overview and explores the potential place in therapy for these agents. Moreover, it addresses their FDA approval timeline and 5-year financial forecast.
Specialty drug names appear in magenta throughout the publication.
avasopasem manganese IV
PROPOSED INDICATIONS
Radiotherapy (RT)-induced severe oral mucositis (SOM) in patients with head and neck cancer (HNC)
CLINICAL OVERVIEW
Avasopasem manganese is a selective dismutase mimetic designed to convert RT-induced bursts of superoxide to hydrogen peroxide in normal cells and cancer cells.
The randomized, double-blind, placebo-controlled, phase 3 ROMAN trial (NCT03689712) evaluated avasopasem manganese in 455 patients with HNC who were receiving intensity-modulated RT (IMRT) plus cisplatin chemotherapy. The study demonstrated a 16% relative reduction in the incidence of SOM (primary endpoint) through the end of the study treatment period (approximately 7 weeks) with avasopasem manganese compared to placebo (54% versus 64%, respectively; p=0.045) and a 56% relative reduction in SOM duration (median, 8 versus 18 days, respectively; p=0.002). In addition, after 1 year of follow-up, tumor outcomes and OS were comparable between the avasopasem manganese and placebo groups. Notably, according to a predefined exploratory analysis, after 1 year of post-treatment follow-up, significantly fewer patients in the avasopasem manganese group developed CKD, a known risk of cisplatin, compared to those in the placebo group (10% versus 20%, respectively; p=0.0043).
Avasopasem manganese 90 mg was infused IV over 60 minutes before each daily (Monday–Friday) RT fraction.
PLACE IN THERAPY
Chemotherapy and RT create reactive oxygen species within cells leading to cell damage and mucositis. Mucositis typically presents during the second or third week of RT and is characterized by erythema and ulceration of the mouth, but can occur throughout the entire GI tract. Approximately 70% of patients with HNC treated with cisplatin plus RT experience SOM (grade 3 or 4). Patients may experience pain and difficulty eating and swallowing warranting the need for enteral/parenteral nutrition, opioids for pain control, and interruption of cancer therapy, if severe. In addition, in immunocompromised patients, SOM may lead to infections, including bacteremia, resulting in hospitalization and increased mortality.
Symptomatic management of mucositis includes basic oral hygiene, dietary modifications, topical agents, and analgesics. Various types of mouthwash found in the literature are suggested to alleviate pain due to oral mucositis (OM). These include oral solutions of doxepin, hydrogen peroxide, normal saline, and baking soda, as well as “miracle” mouthwashes containing combinations of an antacid, diphenhydramine, viscous lidocaine, dexamethasone, nystatin, and/or an antibiotic. The Multinational Association of Supportive Care in Cancer (MASCC) recommends benzydamine mouthwash (anti-inflammatory; not available in the US), intraoral photobiomodulation (PBM) with low-level laser therapy, oral glutamine (off-label), and honey for the prevention of OM in patients with HNC receiving RT and chemotherapy. Topical morphine 0.2% mouthwash is also suggested to treat pain associated with OM. Several mucoadhesive products, considered devices by the FDA, are approved to manage OM symptoms, including Gelclair®, Mugard®, Mucotrol™, and Caphosol®; however, these agents have not been adequately evaluated in well-designed clinical trials.
If approved, avasopasem manganese will be the first systemic therapy for RT-induced SOM. Initial approval is expected for use in patients with HNC. Dusquetide, an innate defense regulator administered via a 4-minute IV infusion every 2 weeks, is in phase 3 trials for OM in patients with HNC receiving RT plus chemotherapy.
FDA APPROVAL TIMELINE
August 9, 2023
Breakthrough Therapy Fast Track Priority Review
FINANCIAL FORECAST (reported in millions)
The financial forecast for avasopasem manganese is not currently available.
Galera
concizumab SC
Novo Nordisk
PROPOSED INDICATIONS
Hemophilia A and B prophylaxis in patients with inhibitors
The randomized, open-label, parallel-group, phase 3 EXPLORER 7 trial (NCT04083781) evaluated prophylactic treatment with concizumab in 132 male patients ≥ 12 years of age with hemophilia A or B with inhibitors. The study reported an estimated mean annualized bleeding rate (ABR) of 1.7 with concizumab compared to 11.8 with no prophylaxis (ABR ratio, 0.14; p<0.001). The median ABR was 0 for concizumab and 9.8 with no prophylaxis. Notably, the EXPLORER clinical program, including the EXPLORER 7 trial, was temporarily placed on hold due to reports of 3 non-fatal thrombotic events in patients who had risk factors at baseline and had used concomitant hemostatic medication (recombinant factor VIIa or VIII). The program resumed after new safety measures were adopted to mitigate this risk. No thrombotic events or other safety concerns were reported after EXPLORER 7 was restarted.
Concizumab was self-administered as a SC injection via a prefilled pen. It was administered as a loading dose of 1 mg/kg on day 1, followed by 0.2 mg/kg once daily starting on day 2. Over the next 5 to 8 weeks, the dose could be adjusted to 0.25 mg/kg or 0.15 mg/kg depending on the concizumab plasma concentrations.
PLACE IN THERAPY
Hemophilia is an X-linked congenital bleeding disorder that affects up to 33,000 males in the US. Hemophilia is characterized by chronic spontaneous bleeding into muscles and joints that can progress to debilitating arthropathy. Hemophilia A and B exhibit low or missing levels of clotting factors VIII and IX, respectively. Hemophilia A and B comprise about 80% and 20% of all cases of hemophilia, respectively. Approximately 35% of patients with hemophilia A and 3% with hemophilia B will develop neutralizing antibodies, or inhibitors, to factor products, which make the condition more difficult to treat.
The bypassing agents, recombinant factor VIIa (e.g., Novoseven RT®, Sevenfact®) and activated prothrombin complex concentrates (e.g., Feiba®), are SOC for managing hemophilia in patients with inhibitors. A hemostatic efficacy of about 80% has been reported with these agents but may vary and change over time. The first FDAapproved non-factor product, emicizumab-kxwh (Hemlibra®), mimics factor VIIIa cofactor and is indicated for routine prophylaxis for patients (newborns through adulthood) with hemophilia A with or without inhibitors. This bispecific factor IXa/X antibody is self-administered SC every 1, 2, or 4 weeks.
If approved, concizumab will be the first anti-TFPI antibody available in the US. In clinical trials, it significantly reduced ABR compared to no prophylaxis. Market uptake could be a challenge due to the need for daily SC injections and by reports of non-fatal thrombosis that led to the halting of early studies. Although, concizumab could find a niche in patients with hemophilia B – a population in which emicizumab-kxwh is not indicated. Novo Nordisk plans to submit concizumab for FDA approval for hemophilia A and B without inhibitors in 2023.
Other non-factor products in phase 3 studies for both hemophilia A and B include the anti-TFPI antibody marstacimab and the small interfering RNA fitusiran. In addition, the first gene therapy for adults with severe hemophilia A, valoctocogene roxaparvovec, is awaiting the FDA decision by June 30, 2023, as a 1-time dose.
FDA APPROVAL TIMELINE
September 2023
Breakthrough Therapy Orphan Drug
FINANCIAL FORECAST (reported in millions)
Year 2023 2024 2025 2026 2027
Projected
Large B cell lymphoma
epcoritamab SC
Genmab/Abbvie
PROPOSED INDICATIONS
Relapsed/refractory (R/R) large B cell lymphoma (LBCL) as ≥ 3rd-line therapy
CLINICAL OVERVIEW
Epcoritamab is a cluster of differentiate 20 (CD20) x cluster of differentiate 3 (CD3) T cell engaging bispecific antibody.
The open-label, phase 1/2 EPCORE NHL-1 trial (NCT03625037) evaluated epcoritamab in 157 adults with R/R LBCL, including diffuse LBCL (DLBCL), high-grade B cell lymphoma, primary mediastinal LBCL, or follicular lymphoma. Enrolled patients received ≥ 2 prior lines of systemic therapy (median, 3; range, 2 to 11), including an anti-CD20 antibody. Among the patients in the study, 39% received prior CAR T cell therapy and 20% had prior autologous SCT. In the phase 2 period, at a median follow-up of 10.7 months (range, 0.3 to 17.9), the ORR (primary endpoint) was 63%, with a complete response rate of 39%. A response was seen in patients with and without prior CAR T therapy (ORR, 54%, and 69%, respectively; complete response rate, 34%, and 42%, respectively). The median time to complete response was 2.7 months (range, 1.2 to 11.1). The estimated median DOR was 12 months (range, 0.3 to 17.9). Among patients who achieved a complete response, 89% maintained that response at 9 months, and the PFS was not reached. CRS occurred in 49.7% of patients, with 2.5% of patients experiencing grade 3 CRS.
In the phase 2 portion of the EPCORE NHL-1 trial, to reduce the risk of serious CRS, patients received priming and intermediate doses of epcoritamab followed by full doses of 48 mg in 28-day cycles. The dosing frequency in cycles 1 through 3 was once weekly, in cycles 4 through 9 was every 2 weeks, and in cycles 10 and beyond was every 4 weeks. Treatment was continued until disease progression or unacceptable toxicity occurred. To further mitigate CRS severity, patients were hospitalized after epcoritamab doses 1 through 4.
The ongoing, open-label, phase 3 EPCORE DLBCL-1 study (NCT04628494) is comparing epcoritamab with investigator’s choice of rituximab ± bendamustine or gemcitabine + oxaliplatin in patients with R/R DLBCL who failed or are ineligible for autologous SCT. Primary data for the study are anticipated in mid-2023.
FDA APPROVAL TIMELINE
May 21, 2023
Priority Review
FINANCIAL FORECAST (reported in millions)
Year 2023 2024 2025 2026 2027
Projected Total US Sales $47 $176 $331 $476 $623
Genentech
PROPOSED INDICATIONS
Relapsed/refractory (R/R) large B cell lymphoma (LBCL) as ≥ 3rd-line therapy
glofitamab
CLINICAL OVERVIEW
Glofitamab is a CD20 x CD3 T cell engaging bispecific antibody.
An open-label, phase 1/2, dose-escalation study (NCT03075696) evaluated glofitamab monotherapy in 154 adults with R/R DLBCL who had received ≥ 2 prior lines of therapy. Approximately one-third of patients had prior CAR T cell therapy. At a median follow-up of 12.6 months (range, 0.1 to 22.1 months), 39% of patients achieved the primary endpoint of complete response. Among those with prior CAR T cell therapy, 35% achieved complete response. Patients achieved a complete response in a median of 42 days. The ORR was 52%, and the 12-month PFS and OS were 37% and 50%, respectively. The most common TEAEs were CRS (63%), neutropenia (38%), anemia (31%), and thrombocytopenia (25%). Serious (grade ≥ 3) events were reported in 62% of patients, including CRS (4%) and neurologic events (3%).
Glofitamab monotherapy was administered IV every 2 or 3 weeks for up to 12 cycles. Patients received stepup doses of 2.5 mg and 10 mg, followed by 30 mg on day 1 of cycles 2 through 12. In addition to step-up dosing, patients received a single dose of obinutuzumab (1,000 mg) 7 days prior to glofitamab treatment to mitigate CRS
FDA APPROVAL TIMELINE
July 1, 2023
Priority Review
FINANCIAL FORECAST (reported in millions)
Year 2023 2024 2025 2026 2027 Projected Total US Sales $0 $96 $136 $202 $245
PLACE IN THERAPY
DLBCL is the most common lymphoid malignancy in adults with over 25,000 new cases diagnosed in the US each year. It is an aggressive mature B cell lymphoma that involves the lymph nodes and often affects the spleen, liver, bone marrow, and other organs. The average age at diagnosis is 64 years. The 5-year survival rate is 64.6%.
Approximately 30% to 40% of DLBCL cases will relapse or progress after initial SOC therapy (R-CHOP). The choice of 2nd-line pharmacotherapy depends on the response to initial therapy, the timing of relapse, and eligibility for HSCT. Preferred 2nd-line regimens may contain platinum-based chemotherapy (± rituximab), CAR T cell therapy, the CD79b-directed ADC polatuzumab vedotin-piiq (Polivy®), or the CD19-directed cytolytic antibody tafasitamab-cxix (Monjuvi®). Current 3rd-line and subsequent therapy options include CAR T therapy, the CD19-directed ADC loncastuximab tesirine-lpyl (Zynlonta®), and the nuclear export inhibitor selinexor (Xpovio®).
HSCT and CAR T cell therapy are proven advancements in the treatment of R/R DLBCL; however, some patients may again relapse or may be ineligible for these therapies. SC-administered epcoritamab and IV glofitamab are bispecific antibodies that bind to CD3 on T cells and CD20 on B cells to induce T cell-mediated tumor cell death. If approved, epcoritamab and glofitamab will provide important targeted therapies for use in heavily treated patients with R/R LBCL. Unlike CAR T, both agents require more than 1 dose. These off-the-self agents are also distinguished from CAR T in that they do not require the collection and genetic modification of patient cells; further, patients are not burdened with traveling to a major academic center for treatment as with CAR T.
Other CD3/CD20 bispecific agents that are in late-phase development for R/R LBCL include mosunetuzumab (phase 3), odronextamab (phase 2), and plamotamab (phase 2).
PROPOSED INDICATIONS
Moderate to severe ulcerative colitis (UC)
CLINICAL OVERVIEW
Etrasimod is a selective sphingosine-1-phosphate (S1P) receptor modulator.
Etrasimod was evaluated in the double-blind, placebo-controlled ELEVATE UC 12 (NCT03996369; n=354) and ELEVATE UC 52 (NCT03945188; n=433) trials in patients ≥ 16 years of age with moderate to severe UC. Approximately one-third of patients in both trials had prior treatment with a biologic agent or Janus kinase (JAK) inhibitor. Patients were randomized 2:1 to etrasimod or placebo. The primary endpoint in both trials was clinical remission as measured by the modified Mayo score (MMS), a composite score consisting of participantreported symptoms (stool frequency [SF] and rectal bleeding [RB]), and a centrally read endoscopic score (ES). Clinical remission was defined as an SF subscore = 0 (or = 1 with a ≥ 1-point decrease from baseline), RB subscore = 0, and ES ≤ 1. In ELEVATE UC 12, at 12 weeks, clinical remission of UC was achieved in significantly more patients treated with etrasimod (25%) than placebo (15%; p=0.026). ELEVATE UC 52 reported significantly higher remission rates with etrasimod compared to placebo at week 12 (27% versus 7%, respectively; p<0.0001) and at week 52 (32% versus 7%; p<0.0001). TEAEs reported more often with etrasimod than placebo were headache, UC worsening, COVID-19 infection, dizziness, pyrexia, arthralgia, abdominal pain, and nausea. No serious bradycardia and atrioventricular block were reported. Two events of symptomatic bradycardia were reported and resulted in study withdrawal. In both studies, the dosage of etrasimod was 2 mg orally once daily.
PLACE IN THERAPY
UC is a chronic inflammatory disease affecting the large bowel (colon and rectum) that is characterized by superficial infiltration of the bowel wall by inflammatory WBCs, resulting in mucosal ulcerations and crypt abscesses. Nearly 1,000,000 people in the US are affected by UC. Onset can occur at any age, but peaks between the ages of 15 to 30 years. Patients experience symptoms such as bloody diarrhea, mucous, bowel urgency, abdominal pressure and cramping, and weight loss that may take on a relapsing/remitting pattern.
Moderate to severe UC is considered when patients are dependent on or refractory to corticosteroids, exhibit ulcers upon endoscopic assessment, or are at high risk for colectomy. Based on current guidelines, 1st-line treatment for moderate to severe UC includes injectable biologic agents, such as TNF-inhibitors (adalimumab [Humira, biosimilar], golimumab [Simponi®], infliximab [Remicade®, biosimilars]), the integrin receptor antagonist vedolizumab (Entyvio®), and the IL-12/IL-23 antagonist ustekinumab (Stelara®). The oral JAK inhibitor tofacitinib (Xeljanz®, Xeljanz® XR) is also used as 1st-line treatment. Long-term management of patients with moderate to severe disease can include biologic agents, tofacitinib, or immunomodulators (e.g., azathioprine, methotrexate). The S1P receptor modulator ozanimod (Zeposia®) was FDA-approved in 2021 for moderate to severe UC in adults and is not addressed in current guidelines.
If approved, etrasimod will compete directly with ozanimod in the UC setting. Both agents are administered orally once daily. Notably, ozanimod requires dose titration to prevent bradycardia and atrioventricular block. It is also contraindicated in patients who experienced prior select CV events (e.g., MI, stroke, unstable angina). In clinical trials, etrasimod was not associated with serious bradycardia or atrioventricular block, and dose titration was not required. In non-comparative clinical trials, 24.8% to 27% of patients treated with etrasimod achieved clinical remission of UC (at week 12) compared to 18% of patients treated with ozanimod.
FDA APPROVAL TIMELINE
July to December 2023
FINANCIAL FORECAST (reported in millions)
Year 2023 2024 2025 2026 2027
Projected Total US Sales $21 $120 $226 $363 $497
lebrikizumab SC
Eli Lilly
PROPOSED INDICATIONS
Moderate to severe atopic dermatitis (AD)
CLINICAL OVERVIEW
Lebrikizumab is an interleukin-13 (IL-13) inhibitor.
The double-blind, placebo-controlled, phase 3 ADvocate 1 (NCT04146363; n=424) and Advocate 2 (NCT04178967; n=472) trials evaluated lebrikizumab monotherapy in patients ages ≥ 12 years (weighing ≥ 40 kg) with moderate to severe AD. Patients were randomized 2:1 to lebrikizumab 500 mg SC initially and at 2 weeks, followed by lebrikizumab 250 mg SC or placebo every 2 weeks. Co-primary endpoints in each trial were an IGA of 0 or 1 (clear or almost clear skin) with a reduction of ≥ 2 points from baseline and EASI-75. In both trials at week 16, significantly more patients on lebrikizumab achieved the IGA endpoint compared to those given placebo (ADvocate 1: 43.1% versus 12.7%, respectively; ADvocate 2: 33.2% versus 10.8%, respectively; p<0.001 for both). Similarly, lebrikizumab led to higher rates of EASI-75 response at week 16 (ADvocate 1: 58.8% versus 16.2%, respectively; ADvocate 2: 52.1% versus 18.1%, respectively; p<0.001 for both). Significant improvements in skin clearing and itching were seen as early as week 4. At week 16, patients who responded to lebrikizumab were re-randomized to lebrikizumab 250 mg every 2 weeks or every 4 weeks or placebo for an additional 36 weeks. At week 52, the studies demonstrated similar and durable responses with lebrikizumab given every 2 and every 4 weeks (IGA 0/1 response rate: ADvocate 1, 76% versus 74%, respectively, and ADvocate 2, 65% versus 81%, respectively; EASI-75 response rate: ADvocate 1, 79% versus 79%, respectively, and ADvocate 2, 77% versus 85%, respectively). Lebrikizumab was well tolerated. The most common TEAEs were conjunctivitis, nasopharyngitis, and headache.
The double-blind, parallel-group, phase 3 ADhere trial (NCT0425033; n=211) evaluated every-2-week SC dosing (after an initial loading dose) of lebrikizumab in combination with a topical corticosteroid (TCS) compared to TCS therapy alone in patients ages ≥ 12 years (weighing ≥ 40 kg) with moderate to severe AD. Medium potency (triamcinolone 0.1%) and low potency (hydrocortisone 1%) TCS creams were used in the study. The patients could taper, stop, and resume TCS therapy as needed. At week 16, significantly more patients achieved an IGA of 0/1 and EASI-75 (co-primary endpoints) in the lebrikizumab/TCS group compared to the placebo/TCS group (IGA 0/1: 41.2% versus 22.1%, respectively [p=0.01]; EASI-75: 69.5% versus 42.2%, respectively [p<0.001]). Lebrikizumab plus a TCS was well tolerated.
PLACE IN THERAPY
AD affects an estimated 31.6 million people in the US, including 9.6 million children and adolescents. Approximately 30% and 40% of cases in pediatrics and adults, respectively, are moderate to severe. The onset of AD occurs before age 6 years in about 80% of cases. While several systemic DMTs are available to treat moderate and severe AD, topical emollients, corticosteroids, and immunomodulators remain important options for treating AD; however, long-term continuous use of TCSs and immunomodulators is limited by TEAEs.
If approved, lebrikizumab will be the second biologic for AD that solely targets IL-13, following tralokinumab’s (Adbry™) approval in December 2021 for use in adults only. Lebrikizumab will compete with tralokinumab and dupilumab (Dupixent®). Dupilumab inhibits IL-4 and IL-13 signaling and is indicated for moderate to severe AD in patients ≥ 6 months of age. Lebrikizumab, tralokinumab, and dupilumab have similar maintenance dosing regimens (every 2 or 4 weeks). Non-comparative clinical trials report greater responses with lebrikizumab monotherapy (IGA difference from placebo range, 22% and 30%; EASI-75 difference from placebo range, 43% and 33%) compared to tralokinumab monotherapy (IGA difference from placebo range, 9% to 12%; EASI-75 difference from placebo range, 12% to 22%). Similar responses were reported in non-comparative trials with lebrikizumab and dupilumab (dupilumab IGA difference from placebo, 28%; EASI-75 difference from placebo range, 32% to 36%).
lebrikizumab cont.
FDA APPROVAL TIMELINE
September 2023
Fast Track
FINANCIAL FORECAST (reported in millions)
Tarsus
PROPOSED INDICATIONS
Demodex blepharitis
CLINICAL OVERVIEW
Lotilaner ophthalmic solution is a gamma-aminobutyric acid-gated chloride channel (GABA-Cl) inhibitor designed to eradicate Demodex mite infestation.
The randomized, vehicle-controlled, double-masked, phase 2b/3 Saturn-1 (NCT04475432; n=421) and phase 3 Saturn-2 (NCT04784091; n=412) trials evaluated lotilaner in patients with Demodex blepharitis. Enrolled participants displayed > 10 collarettes (cylindrical dandruff) per eyelid, at least mild upper eyelid margin erythema, and ≥ 1.5 mites/lash on upper/lower eyelids. In both trials, significantly more patients treated with lotilaner achieved the primary endpoint of complete collarette cure (0 to 2 collarettes per upper eyelid) at day 43 compared to patients who received vehicle (Saturn 1: 44% versus 7.4%, respectively; Saturn 2: 56% versus 13%, respectively; p<0.0001 for both). In addition, significantly more patients achieved the following secondary endpoints with lotilaner compared to the vehicle: mite eradication (Saturn 1: 67.9% versus 17.6%; respectively; Saturn 2: 52% and 14%, respectively; p<0.0001 for both), complete eyelid erythema cure (Saturn 1: 19.1% versus 6.9%, respectively; Saturn 2: 31.1% versus 9%; p<0.0001 for both), and complete composite (collarette + erythema) cure (Saturn 1: 13.9% versus 1%, respectively; Saturn 2: 19.2% versus 4%, respectively; p < 0.0001 for both). The Saturn 1 study also reported that significant improvement was observed as early as day 8 in the primary and some secondary endpoints. Lotilaner was well tolerated. The most common TEAE was instillation site pain/burning/stinging (7.9%). In a phase 2 trial, collarette grade and mite density improvements were maintained 2 months after stopping therapy.
Lotilaner 0.25% ophthalmic solution was administered as 1 drop in each eye twice daily for 43 days, with no eyelid intervention such as eyelid hygiene.
PLACE IN THERAPY
Demodex is a common parasite of the skin and inhabits the eyelashes, eyebrows, and face. As detected on slit-lamp examination, the presence of waxy deposits called collarettes, or cylindrical dandruff or “sleeves,” on eyelashes is an indicator of Demodex infestation. Collarettes contain lipids, keratin, Demodex eggs, and/ or dead Demodex mites. Common symptoms of Demodex blepharitis include swollen, red, irritated eyelids, and ocular itching. Patients may also experience eyelash loss, dry eyes, and recurrent styes or chalazia. It is estimated that Demodex blepharitis affects 10 million people in the US. If not properly diagnosed, patients may be prescribed medications to treat ocular sequalae of the condition (e.g., dry eye), rather than the underlying cause, and if left untreated it can lead to serious corneal conditions.
There are no FDA-approved treatments for Demodex blepharitis. Therapies cited in the literature provide mixed results. The topical application of tea tree oil (weekly scrub or daily shampoo) or its active ingredient, terpinen-4-ol (wipe), is commonly used. Off-label use of oral or topical ivermectin, topical metronidazole, permethrin, or crotamiton has also appeared in the literature.
Lotilaner is a topical antiparasitic agent that paralyzes and eradicates Demodex mites. If approved, it will be the first agent indicated in the US to treat Demodex blepharitis. In clinical studies, it resulted in a clinical cure and a favorable safety profile. Notably, the active ingredient lotilaner is approved as oral tablets (brand Credelio®) for the prevention of fleas and ticks in dogs and cats. Oral or other systemic formulations of lotilaner are not approved for use in humans.
FDA APPROVAL TIMELINE
August 25, 2023
FINANCIAL FORECAST (reported in millions)
Year 2023 2024 2025 2026 2027
Projected Total US Sales* $3 $74 $180 $297 $414
* Forecasted sales reported for all investigational indications
GlaxoSmithKline
PROPOSED INDICATIONS
Myelofibrosis (MF)
CLINICAL OVERVIEW
Momelotinib is an inhibitor of Janus kinase (JAK) 1 and 2 and activin A receptor, type 1 (ACVR1). JAK 1/2 inhibition is designed to improve myelofibrosis symptoms and splenomegaly, and ACVR1 inhibition decreases circulating hepcidin, which contributes to anemia.
The randomized, double-blind, parallel-group, phase 3 MOMENTUM trial (NCT04173494) compared momelotinib and danazol in 195 symptomatic, anemic (Hb < 10 g/dL) adults with primary myelofibrosis (PMF), post-polycythemia vera (PV) myelofibrosis, or post-essential thrombocythemia (ET) myelofibrosis. All patients were previously treated with a JAK inhibitor (ruxolitinib) and had palpable splenomegaly at baseline. In the momelotinib and danazol groups, 72% and 58% of patients, respectively, completed 24 weeks of treatment, with adverse reactions as the most common reason for discontinuation. At 24 weeks, momelotinib proved to be superior to danazol in the primary endpoint of the proportion of patients achieving a ≥ 50% reduction from baseline in the Myelofibrosis Symptom Assessment Form Total Symptom Score (MSA TSS) (25% versus 9%, respectively; p=0.0095) and the secondary endpoints of ≥ 25% reduction in spleen volume (40% versus 6%, respectively; p<0.0001) and ≥ 35% reduction in spleen volume (23% versus 3%, respectively; p=0.0006). In addition, momelotinib was non-inferior to danazol, based on transfusion independence at 24 weeks (31% versus 20%, respectively; p=0.0064). The most common serious (grade ≥ 3) TEAEs in each group were anemia (61% versus 75%, respectively) and thrombocytopenia (28% versus 26%, respectively).
The randomized, double-blind, phase 3 SIMPLIFY-1 trial (NCT01969838) compared momelotinib and the JAK inhibitor ruxolitinib in 432 JAK inhibitor-naïve adults with PMF, post-PV myelofibrosis, or post-ET myelofibrosis. Enrollees had anemia (Hb < 10 g/dL), symptomatic splenomegaly or hepatomegaly, and/or were unresponsive to available non-JAK inhibitor myelofibrosis therapy. At week 24, momelotinib was shown to be non-inferior to ruxolitinib, based on the proportion of patients who achieved the primary endpoint of ≥ 35% reduction in spleen volume (26.5% and 29%). However, fewer patients who received momelotinib compared to those given ruxolitinib achieved a ≥ 50% reduction in the MSA TSS, a secondary endpoint (28.4% versus 42.2%, respectively). Notably, more patients in the momelotinib group were transfusion independent at week 24 (66.5%) compared to the ruxolitinib group (49.3%; nominal p<0.001). The median rate of RBC transfusion through week 24 was 0 units/month with momelotinib compared to 0.4 units/month with ruxolitinib (nominal p<0.001).
The randomized, open-label, phase 3 SIMPLIFY-2 trial (NCT02101268) compared momelotinib to the best available therapy (BAT) for MF, which included hydroxyurea, anagrelide, corticosteroids, hematopoietic growth factors, immunomodulating agents, androgens, and interferon. Patients (n=156) enrolled had PMF, post-PV myelofibrosis, or post-ET myelofibrosis with palpable splenomegaly and either anemia or thrombocytopenia. All patients were previously treated with ruxolitinib. At 24 weeks, 7% of patients in the momelotinib group and 6% in the BAT group achieved the primary endpoint of ≥ 35% reduction in spleen volume from baseline (p=0.9); momelotinib was not superior to BAT.
In the phase 3 trials, the doses studied were momelotinib 200 mg orally once daily, ruxolitinib 20 mg orally twice daily, and danazol 300 mg orally twice daily. Dose interruptions or reductions due to thrombocytopenia, neutropenia, or other toxic effects were permitted.
momelotinib cont.
PLACE IN THERAPY
Myelofibrosis (MF) is a rare, myeloproliferative neoplasm (MPN) characterized by the overproduction of abnormal hematopoietic stem cells and scarring (fibrosis) within the bone marrow. Anemia and thrombocytopenia are usually present, particularly as the disease progresses. Notably, a Hb < 10 g/dL is an unfavorable prognostic marker. Splenomegaly is also common. It is estimated that 13,000 people in the US have MF. The median age at diagnosis is 65 years, although it can occur at any age. Most often (> 50%) MF is idiopathic (primary) in nature, but it can also be secondary to a malignant or hematologic condition, such as polycythemia vera and essential thrombocythemia (10% to 15%). Primary MF may progress slowly, and patients may be asymptomatic for many years; however, some cases may transform into acute myeloblastic leukemia (AML). Several gene mutations have been identified with MPNs. Approximately 60% of patients with primary MF have a V617F JAK2 gene mutation, which is associated with a median survival period of 9 years.
In asymptomatic MF patients, clinicians may adopt a watch-and-wait approach. In early primary MF, pegylated interferon may reduce bone marrow fibrosis and spleen size in low-risk patients. Allogeneic HSCT may be curative in patients with advanced MF, but the associated morbidity and mortality risks limit its use in patients with advanced disease. Palliative therapy for MF includes androgens, erythropoietin, hydroxyurea, thalidomide, lenalidomide, corticosteroids, radiation therapy, chemotherapy, splenectomy or splenic embolization, and RBC and/or platelet transfusions. The only FDA-approved treatments for MF are the oral JAK inhibitors. This includes ruxolitinib (Jakafi®; JAK1/2 inhibitor; therapy of choice) and fedratinib (Inrebic®; selective JAK2 inhibitor), both of which are indicated for the treatment of intermediate- or high-risk primary or secondary MF in patients with platelet count > 50,000/µL, and pacritinib (Vonjo™; JAK2 and FLT3 inhibitor), which is approved for use in patients with platelet count < 50,000/µL. For patients with anemia associated with MF, after ruling out other causes for anemia (e.g., bleeding or iron, vitamin B12, or folate deficiencies), the NCCN recommends erythropoietin stimulating agents (ESAs), danazol, lenalidomide, or thalidomide, depending on serum erythropoietin levels.
Momelotinib is a first-in-class inhibitor of both JAK1/2 and ACVR1. If approved, it will be the first JAK inhibitor to target myelofibrosis in patients with anemia. In clinical trials, momelotinib led to greater improvements in MF symptoms and spleen volume compared to danazol, but not compared to ruxolitinib. A greater improvement in anemia (transfusion independence) was reported with momelotinib over both danazol and ruxolitinib.
FDA APPROVAL TIMELINE
June 16, 2023
Fast Track
Orphan Drug
FINANCIAL FORECAST (reported in millions) Year 2023 2024 2025 2026 2027
Projected Total US Sales $11 $52 $90 $130 $169
INFECTIOUS DISEASE
IM
AstraZeneca/Sanofi
PROPOSED INDICATIONS
Prevention of respiratory syncytial virus (RSV) lower respiratory tract infection (LRTI) in newborns and infants during their first RSV season and in children ≤ 24 months of age who are at risk for severe RSV disease through their second RSV season
CLINICAL OVERVIEW
Nirsevimab is a long-acting recombinant human IgG1kappa monoclonal antibody that binds the F1 and F2 subunits of the RSV fusion (F) protein, thereby blocking viral entry into the host cell.
The international, double-blind, placebo-controlled, phase 3 MELODY trial (NCT03979313) evaluated nirsevimab in healthy infants born at a gestational age (GA) of ≥ 35 weeks 0 days who were ≤ 1 year of age and who were entering their first RSV season. Patients were randomized 2:1 to a single IM dose of nirsevimab or matching placebo that was administered before the start of the RSV season. The primary endpoint was medically attended RSV-associated LRTI through 150 days after the dose. Based on published interim data that included 1,490 patients, the primary endpoint occurred in 1.2% of patients in the nirsevimab group and 5% in the placebo group, demonstrating a 74.5% efficacy against medically attended RSV-associated LRTI for nirsevimab. Nirsevimab was generally well tolerated; however, serious adverse events were reported in 6.8% and 7.3% of patients in the nirsevimab and placebo groups, respectively. Three deaths occurred between day 140 and 361, all among patients in the nirsevimab group; 2 deaths were due to gastroenteritis and 1 death due to an unknown cause. An updated analysis that included data from a total of 3,012 patients reported similar findings, with a 76.4% efficacy against medically-attended RSV-associated LRTI with nirsevimab. In the full cohort, nirsevimab also demonstrated a 76.8% efficacy against RSV LRTI-related hospitalization, a 78.6% efficacy against very severe medically attended RSV LRTI, and a favorable tolerability profile.
In a post hoc analysis of pooled data from the MELODY trial and a phase 2b trial, RSV neutralizing antibodies were detected in blood from nirsevimab-treated infants 151 days after the dose. Levels were approximately 50 times higher than at baseline and remained over 19 times higher than levels in placebo-treated infants through day 361.
The double-blind, phase 2/3 MEDLEY trial (NCT03959488) compared the safety and pharmacokinetics of nirsevimab and palivizumab in a total of 925 preterm infants (born at GA ≤ 35 weeks) OR infants with chronic lung disease (CLD) or congenital heart disease (CHD) of prematurity. All patients were at high risk for RSV LRTI and eligible for palivizumab therapy. Prior to RSV season 1, all patients were randomized 2:1 to nirsevimab (1 weight-based dose followed by 4 monthly placebo doses) or palivizumab (15 mg/kg for 5 monthly doses).
Patients with CLD or CHD also received the study drug prior to RSV season 2. Those originally assigned to nirsevimab continued with nirsevimab, and those originally assigned to palivizumab were re-randomized to either nirsevimab or palivizumab. The study showed similar safety and tolerability profiles between both agents. However, 2 serious TEAEs were reported in the nirsevimab group; heparin-induced thrombocytopenia in an infant with CHD and maculopapular rash following a placebo dose. In addition, 4 (0.6%) infants receiving nirsevimab and 3 (1%) receiving palivizumab had medically attended RSV LRTI.
In both clinical trials, nirsevimab was administered IM as 50 mg in patients weighing < 5 kg or 100 mg in patients weighing ≥ 5 kg prior to the start of the RSV season.
PLACE IN THERAPY
RSV is a common contagious respiratory virus that usually causes mild, cold-like symptoms lasting 1 to 2 weeks. In the US each year, RSV infection leads to approximately 2.1 million outpatient visits, 58,000 to 80,000 hospitalizations, and 100 to 300 deaths in children < 5 years of age. Children who are at particular risk for serious RSV infections are premature infants, children < 2 years of age with CLD or CHD of prematurity, and children who are immunocompromised or have neuromuscular disorders.
Typically, the RSV season in the US occurs during approximately November through April but may vary by region. However, the regular RSV circulation pattern was disrupted by the COVID-19 pandemic, leading to interseasonal variability. There is no FDA-approved medication to treat RSV or vaccine to prevent RSV illness in the pediatric population. Treatment of mild cases consists of symptom management, including use of antipyretics and analgesics; however, palivizumab (Synagis®), an RSV F protein inhibitor monoclonal antibody, is the only agent FDA-approved for the prevention of RSV. It is indicated for use only in infants and young children who are at high risk for serious RSV LRTI (preterm infants < 6 month of age and children ≤ 24 months of age with CLD or CHD of prematurity). Palivizumab is typically administered once monthly per IM injection for 5 consecutive doses beginning just before the start of the RSV season, as based on the American Academy of Pediatrics guidelines. However, during the period of an unusual RSV circulating pattern observed during the COVID-19 pandemic, additional or off-season doses may have been warranted.
If approved, nirsevimab will be the first single-dose option to prevent RSV LRTI. It could also provide protection for a broader pediatric population, including healthy infants, whereas palivizumab requires monthly dosing for use only in high risk patients. Nirsevimab demonstrated comparable safety and tolerability as palivizumab and may provide enhanced viral efficacy against RSV-related hospitalization in at-risk children, as suggested in the MEDLEY trial and non-comparison study data.
Other products in the pipeline for RSV include Merck’s monoclonal antibody clesrovimab, which is in phase 3 trials for use in patients < 1 year of age who are at increased risk for severe RSV infection. Pfizer’s RSV vaccine candidate (PF-06928316) has been submitted to the FDA for maternal administration during pregnancy to protect the infant from RSV after birth and has the potential to be the first RSV vaccine approved to protect infants from RSV LRTI. Novavax’s RSV vaccine is also in phase 3 research for maternal administration.
RSV can also cause serious illness in older adults. Two RSV vaccines by GlaxoSmithKline (GSK3844766A) and Pfizer (PF-06928316) have been submitted to the FDA for prevention of RSV in older adults (≥ 60 years of age). The FDA decisions for these vaccines are anticipated in May 2023.
FDA APPROVAL TIMELINE
July to September 2023
Breakthrough Therapy Fast Track
FINANCIAL
FORECAST
(reported in millions)
Year 2023 2024 2025 2026 2027
Projected Total US Sales $144 $364 $547 $718 $823
INFECTIOUS DISEASE
PROPOSED INDICATIONS
Invasive fungal infections in patients who have limited or no treatment options
CLINICAL OVERVIEW
Olorofim is an orotomide antifungal. It inhibits the dihydroorotate dehydrogenase (DHODH) enzyme in the fungal pyrimidine synthesis pathway resulting in cell death. It has shown in vitro activity against Aspergillus species (spp). (including azole-resistant and cryptic species), rare molds (e.g., Lomentospora prolificans, Scedosporium spp., Scopulariopsis spp.), and dimorphic fungi (e.g., Histioplasma spp., Blastomyces spp., Coccidioides spp.).
The ongoing, open-label, phase 2b FORMULA-OLS trial (NCT03583164) evaluated olorofim in adults with resistant invasive fungal disease due to Lomentospora prolificans, Scedosporium spp., Aspergillus spp., or other resistant fungi lacking appropriate treatment options. Patients 16 or 17 years of age weighing ≥ 40 kg were also allowed study entry. Patients received olorofim for up to 90 days (median, 84 days). Approximately 75% of the first 100 patients had moderate to high levels of immunosuppression. Data from the first 100 patients revealed that at day 42, the ORR was 69%, including stable response. A complete or partial response was observed in 44% of patients. At days 42 and 84, the rates for all-cause mortality were 15% and 20%, respectively. Olorofim was generally well tolerated. Nausea, vomiting, and diarrhea were reported. Eight patients (8%) experienced drug-induced liver injury, a serious adverse effect possibly related to olorofim; 2 (2%) patients were required to discontinue therapy.
Olorofim was administered orally as an initial loading dose of 150 mg twice daily on day 1, followed by 90 mg twice daily for up to 90 days.
PLACE IN THERAPY
Invasive fungal infections cause considerable morbidity and mortality, particularly among immunocompromised patients. Antifungal agents that have been approved in the past 20 years to fight invasive fungal infections include azoles (e.g., extended-spectrum triazoles, voriconazole, posaconazole, and isavuconazole); amphotericin B lipid formulations; and the echinocandins. However, current antifungals have limitations, including limited dosage forms, drug-drug interactions, and significant adverse reactions. The increase in fungal pathogens resistant to current antifungals adds to the increased need for new treatment options.
Olorofim is a first-in-class orotomide antifungal. Its ability to reversibly inhibit fungal DHODH, a key enzyme in the biosynthesis of pyrimidines, leads to impairment of nucleic acid production and fungal cell lysis. This mechanism of action allows for activity against isolates that are resistant to current treatment options. Olorofim is active against many molds and dimorphic fungi, including species that are resistant to azoles and amphotericin B. However, it lacks activity against yeasts, including Candida spp. and Cryptococcus spp., and the Mucorales group. Olorofirm exhibits time-dependent fungicidal activity and wide tissue distribution, including the CNS. Olorofim is metabolized by multiple CYP450 enzymes, including CYP3A4; however, based on current evidence, it does not appear to have any effect on CYP450 enzymes, and therefore, may have limited potential for drug-drug interactions.
If approved, olorofim may be an important oral option for patients with invasive fungal infections, including patients with immunocompromise, limited treatment options, or with difficult-to-treat organisms. Olorofim does not possess broad-spectrum antifungal activity, but it may play a key role in treating multi-drug resistant fungal infections and/or endemic mycoses. F2G has initiated the phase 3 OASIS trial comparing olorofim with liposomal amphotericin B injection (Ambisome®) followed by SOC to treat invasive aspergillosis of the lower respiratory tract.
FDA APPROVAL TIMELINE
June 17, 2023
Breakthrough Therapy
LPAD
Orphan Drug
FINANCIAL FORECAST (reported in millions)
The financial forecast for olorofim is not currently available.
QIPD
BEHAVIORAL HEALTH
zuranolone oral
Sage/Biogen
PROPOSED INDICATIONS
» Major depressive disorder (MDD)
» Postpartum depression (PPD)
CLINICAL OVERVIEW
Zuranolone is a neuroactive steroid that acts as a positive allosteric GABA-A receptor modulator. It is designed to rapidly rebalance dysregulated neuronal networks in the brain that affect mood, arousal, behavior, and cognition.
Zuranolone is being evaluated in adults with moderate or severe MDD across several randomized, doubleblind (unless otherwise noted), placebo-controlled, phase 3 clinical trials. Baseline HAMD-17 scores were ≥ 24 in WATERFALL and CORAL, ≥ 22 in MOUNTAIN, and ≥ 20 in SHORELINE.
» The 42-day WATERFALL trial (NCT04442490; n=543) demonstrated significant improvement from baseline with zuranolone 50 mg compared to placebo in depressive symptoms, based on HAMD-17 score at day 15 (primary endpoint; difference, −1.7; p=0.0141). A significant difference compared to placebo was seen as early as day 3 (difference, −3; p<0.0001). A significant improvement in anxiety based on HAM-A score was also reported at day 8 (difference, -1.7; p=0.0011) and day 15 (difference, -1.4; p=0.0199). Numerical improvements were maintained through day 42.
» The CORAL study (NCT04476030; n=440) evaluated zuranolone 50 mg co-initiated with a SOC antidepressant (SSRI, SNRI) in adults with MDD with elevated anxiety. The mean change in HAMD-17 score from baseline to day 3 (primary endpoint) was -8.9 with combination therapy, compared to -7 with SOC alone (p=0.0004). The mean changes over the 14-day treatment period were -11.7 and -10.1, respectively (the difference was not statistically significant).
» The MOUNTAIN study (NCT03672175) enrolled patients with an HDRS-17 (a.k.a. HAMD-17) total score ≥ 22. Based on a post hoc analysis, patients who received zuranolone 30 mg (n=194) experienced significant improvement in HDRS-17 total score compared to those who received placebo (n=193) at days 3, 8, 12, and 15 (p<0.05 at all time points). In a blinded follow-up, the response was maintained in 74.5% of responders to zuranolone 30 mg at day 182.
» The ongoing, open-label, 1-year longitudinal SHORELINE study (NCT03864614) assessed the need for retreatment after a 14-day course of zuranolone. Patients initiated therapy with zuranolone 30 mg (n=725) or 50 mg (n=52), which led to mean changes in their HAMD-17 scores from baseline to day 15 by -14.9 and -16, respectively. Among those who received zuranolone 30 mg, 71.6% achieved a response (HAMD-17 reduced by ≥ 50%) and 39.8% achieved remission (HAM-D ≤ 7). Likewise, initial doses of 50 mg resulted in a response rate of 74.9% and a remission rate of 40.2%. During the year-long study, retreatment was reported in 55.5% (mean, 1.9 treatments per year) of patients who responded to initial treatment with zuranolone 30 mg and 45.2% (range, 1 to 5 treatment courses) of those who responded to initial treatment with zuranolone 50 mg. Updated data revealed that the median times to first retreatment were 135 and 249 days with zuranolone 30 mg and 50 mg, respectively. No significant difference in response was observed between patients who were on pre-existing antidepressants and those who were not taking other antidepressant agents.
The randomized, double-blind, placebo-controlled ROBIN and SKYLARK trials evaluated zuranolone in adult women with PPD (HAMD-17 ≥ 26) that began no earlier than the third trimester and no later than the first 4 weeks following delivery. Additionally, patients were ≤ 6 months (ROBIN) or ≤ 12 months (SKYLARK) postpartum.
» In ROBIN (NCT02978326; n=153), a statistically significant improvement in depressive symptoms as based on the HAMD-17 score was observed at day 15 (primary endpoint) with zuranolone 30 mg compared to placebo (−17.8 versus −13.6, respectively; p=0.003). Significant differences in HAMD-17 between zuranolone 30 mg and placebo were reported as early as day 3 (difference, -2.7; p=0.03) and at day 45 (difference, -4.1; p=0.003).
zuranolone cont.
CLINICAL
OVERVIEW cont.
» In SKYLARK (NCT04442503; n=195), a statistically significant and clinically meaningful improvement in the HAMD-17 score was observed at day 15 (primary endpoint) with zuranolone 50 mg compared to placebo (−15.6 versus −11.6, respectively; p=0.0007). More patients in the zuranolone group achieved response (reported at days 3 through 28; p<0.05 at all time points) or remission (reported on day 3 and day 45; p<0.05 at day 45) than in the placebo group. Significant improvements in anxiety were also reported with zuranolone compared to placebo.
In the MDD and PPD studies, zuranolone was dosed orally once daily for 14 consecutive days. The drug was generally well tolerated. The most common TEAEs included somnolence, dizziness, headache, fatigue, diarrhea, nausea, and sedation. In the SHORELINE trial, more frequent TEAEs were reported with the 50 mg dose compared to 30 mg, but the severity of TEAEs was similar between the groups. Weight gain, sexual dysfunction, and sleep disruption were not observed with zuranolone. One patient in the ROBIN trial zuranolone group experienced a serious adverse event of confusion. Similar efficacy and safety were reported in patients ≥ 65 years of age and younger populations with MDD.
PLACE IN THERAPY
MDD is defined as a depressed mood or loss of interest in daily activity with a majority of certain symptoms (e.g., difficulty sleeping, impaired concentration, negative self-worth) lasting ≥ 2 weeks. It is one of the most common mental disorders in the US, with an estimated 21 million adults reporting at least 1 MDD episode in 2020 and 14.8 million reporting severe impairment. Prevalence is higher among females than males (10.5% and 6.2%, respectively) and is highest among those 18 to 25 years of age. First-line pharmacotherapy for MDD includes an SSRI, SNRI, bupropion, or mirtazapine. Select atypical anti-psychotics may be added when an adequate response is not achieved after multiple trials with an antidepressant alone.
The CDC reports that about 1 in 8 women with a recent live birth experience symptoms of PPD, including intense feelings of sadness, anxiety, or despair that interfere with activities of daily living. PPD symptoms may occur up to 1 year after delivery. Primary treatment includes cognitive behavioral therapy and interpersonal therapy, particularly in patients who are breastfeeding; however, antidepressant medication, notably SSRIs in breastfeeding women, may be considered. Sage Therapeutics’ IV-administered neuroactive steroid GABA-A receptor positive modulator brexanolone (Zulresso®) is FDA-approved for the treatment of PPD in females ≥ 15 years of age. Brexanolone (Zulresso) is a schedule IV controlled substance that may cause excessive sedation and sudden loss of consciousness; therefore, it must be administered in a certified healthcare facility to allow for continuous monitoring during the 60-hour single-dose infusion and the patient and facility must enroll in the REMS program.
If approved, oral zuranolone could fill an unmet need in patients experiencing moderate to severe MDD. Its unique dosing, rapid onset (as early as 3 days), short duration of therapy (14 days), and proven safety and efficacy with retreatment could change how patients are treated for depression, as well as how follow-up care is administered. In contrast, currently available antidepressants (e.g., SSRIs, SNRIs) require long-term continuous use and take 6 to 8 weeks to realize their full effect. An exception to this is intranasal esketamine (Spravato®), an N-methyl D-aspartate (NMDA) receptor antagonist indicated in conjunction with an oral antidepressant for resistant MDD or MDD associated with suicidal ideation or behavior. Esketamine has demonstrated an onset of effect for MDD as early as 24 hours. However, unlike zuranolone, the schedule III controlled substance esketamine carries risks of abuse and misuse and may cause sedation and dissociation after administration; therefore, patients must be monitored for at least 2 hours after each dose.
Zuranolone could also be an oral alternative to IV brexanolone (Zulresso) for PPD. Symptoms of excessive sedation and loss of consciousness that are seen with IV brexanolone have not been reported with oral zuranolone. It remains to be seen whether oral zuranolone’s labeling will carry boxed warnings regarding excessive sedation or loss of consciousness, similar to brexalonone, or warnings regarding suicidal thoughts and behaviors, like other oral antidepressants. In clinical trials, women receiving oral zuranolone were not permitted to breastfeed during treatment and for 7 days after the last dose.
zuranolone cont.
FDA APPROVAL TIMELINE
August 5, 2023
The FDA advisory committee is not anticipated to review the NDA for zuranolone.
Breakthrough Therapy Fast Track Priority Review
FINANCIAL FORECAST (reported in millions)
Biosimilar Overview
CLINICAL OVERVIEW
Biosimilars are very different from generic drugs in that they are not exact duplicates of their reference biologic product. The FDA approval process for biosimilars is designed to ensure that the biosimilar product is highly similar to the reference product without having any meaningful clinical differences. Moreover, an interchangeable biological product is a biosimilar that is expected to produce the same clinical result as the reference product in any given patient. Switching or alternating between the reference and interchangeable products should have been evaluated and should not negatively impact the safety and efficacy of therapy.
Many controversies have surrounded biosimilars, and regulatory and litigation hurdles remain. The FDA has issued final and draft guidances. Select FDA biosimilar guidances are noted here. In January 2017, the agency issued final guidance on the nonproprietary naming of biologic products, which also applies to biosimilars. The biological products must bear a core name followed by a distinguishing 4-letter, lowercase, hyphenated suffix that is devoid of meaning. The international nonproprietary name (INN) impacts interchangeability as it affects pharmacists’ ability to substitute an interchangeable biosimilar for the reference product.
The FDA withdrew the September 2017 draft industry guidance on determining similarity of a proposed biosimilar product to its reference product to allow for further consideration of the most current and relevant scientific methods in evaluating analytical data. The agency focuses on providing flexibility for the efficient development of biosimilars while maintaining high scientific standards. In July 2018, the FDA finalized its guidance on labeling biosimilars. The guidance pertains to prescribing information (PI) but does not contain specific recommendations on interchangeability in the labeling. The labeling guidance provides recommendations on how to include, identify, and differentiate the biosimilar and the reference product in various sections of the PI. The basic premise remains that the originator product’s safety and effectiveness can be relied upon for HCPs to make prescribing decisions; therefore, a biosimilar should include relevant data from the originator in its PI. In May 2019, the agency released its final guidance on interchangeability. Most states have enacted biosimilar substitution laws. An interchangeable product may be substituted for the originator at the pharmacy without the involvement of the prescriber. In December 2022, the FDA announded a pilot regulatory science program that focuses on advancing the development of interchangeable products and improving the efficiency of biosimilar product development. The Purple Book is an FDA database of licensed biological products that lists biosimilar and interchangeable products. The FDA has approved 3 biosimilars for interchangeability to their reference product: insulin glargine-yfgn (Semglee®), adalimumabadbm (Cyltezo®), and ranibizumab-eqrn (Cimerli™).
Biosimilars can receive extrapolation to gain an indication without direct trials of the biosimilar for the eligible indication(s) of the reference products without requiring additional trials. Nevertheless, as each biosimilar comes to market, it will need to be considered individually. The FDA historically regulated insulins as small molecules. However, effective March 23, 2020, drugs such as insulin and growth hormone were deemed biologics and transitioned from the drug pathway to the biologic pathway. Their licensure as biologics allows these agents to be considered in the biosimilar space and promotes competition and access.
PLACE IN THERAPY
The patents of several biologic drugs are set to expire in the next few years, opening the US market for biosimilar entry; however, patent litigation has resulted in significant launch delays of FDA-approved biosimilars. In June 2017, the US Supreme Court issued 2 landmark rulings: (1) allowing a biosimilar manufacturer to provide launch notice of commercial marketing to the originator manufacturer before or after FDA approval of the biosimilar product and (2) eliminating any federal requirement for disclosure, also known as the “patent dance.” Some states, however, mandate disclosure. These decisions may bring biosimilars to the market sooner and potentially create price competition in the marketplace.
In July 2018, the FDA unveiled its Biosimilar Action Plan (BAP), a series of 11 steps to encourage biosimilar market competition, some of which were previously announced or underway. The BAP contains 4 key strategies: (1) improve the biosimilar development and approval process; (2) maximize scientific and regulatory clarity for sponsors; (3) provide effective communications for patients, clinicians, and payers; and (4) reduce unfair tactics that may delay market approval and entry. The BAP strives to promote access to biosimilar products and reduce healthcare costs.
To date, a total of 40 biosimilars have received FDA approval. Of these, only 30 have entered the market.
APPROVED BIOSIMILARS
Brand Name (Nonproprietary name)
Zaxio® (filgrastim-sndz)
Inflectra® (infliximab-dyyb)
Erelzi® (etanercept-szzs)
Amjevita™* (adalimumab-atto)
Renflexis® (infliximab-abda)
Cyltezo* (adalimumab-adbm)
Mvasi® (bevacizumab-awwb)
Ixifi™ (infliximab-qbtx)‡
Ogivri® (trastuzumab-dkst)
Retacrit® (epoetin alfa-epbx)
Fulphila® (pegfilgrastim-jmdb)
Nivestym® (filgrastim-aafi)
Hyrimoz®* (adalimumab-adaz)
Udenyca® (pegfilgrastim-cbqv)
Truxima® (rituximab-abbs)
Herzuma® (trastuzumab-pkrb)
Ontruzant® (trastuzumab-dttb)
Trazimera™ (trastuzumab-qyyp)
Eticovo™ (etanercept-ykro)
Kanjinti® (trastuzumab-anns)
Zirabev® (bevacizumab-bvzr)
Hadlima™*† (adalimumab-bwwd)
Ruxience® (rituximab-pvvr)
Sandoz March 2015
Pfizer April 2016
Sandoz August 2016
Amgen September 2016
Merck/Organon May 2017
Boehringer Ingelheim August 2017
Amgen September 2017
Pfizer December 2017
Mylan/Biocon December 2017
Pfizer/Vifor/ Hospira May 2018
Mylan/Biocon June 2018
Pfizer July 2018
Sandoz October 2018
Coherus November 2018
Cephalon/Teva November 2018
Teva December 2018
Merck January 2019
Pfizer March 2019
Merck April 2019
Amgen June 2019
Pfizer June 2019
Organon July 2019
Pfizer July 2019
(Manufacturer)
Neupogen® (Amgen)
Remicade (Janssen)
Enbrel® (Amgen)
Humira (Abbvie)
Remicade (Janssen)
Humira (Abbvie)
Avastin® (Genentech)
Remicade (Janssen)
Herceptin® (Genentech)
Epogen® (Amgen) Procrit® (Janssen)
Neulasta® (Amgen)
Neupogen (Amgen)
Humira (Abbvie)
Neulasta (Amgen)
Rituxan® (Genentech)
Herceptin (Genentech)
Herceptin (Genentech)
Herceptin (Genentech)
Enbrel (Amgen)
Herceptin (Genentech)
Avastin (Genentech)
Humira (Abbvie)
Rituxan (Genentech)
Brand Name (Nonproprietary name) Manufacturer
Abrilada™* (adalimumab-afzb)
Ziextenzo® (pegfilgrastim-bmez)
Avsola® (infliximab-axxq)
Nyvepria™ (pegfiltrastim-apgf)
Semglee (insulin glargine-yfgn)
Hulio®* (adalimumab-fkjp)
Riabni™ (rituximab-arrx)
Byooviz™ (ranibizumab-nuna)
Rezvoglar™ (insulin glargine-aglr)
Yusimry™* (adalimumab-aqvh)
Releuko® (filgrastim-ayow)
Alymsys® (bevacizumab-maly)
Fylnetra® (pegfilgrastim-pbbk)
Cimerli (ranibizumab-eqrn)
Stimufend® (pegfilgrastim-fpgk)
Vegzelma® (bevacizumab-adcd)
Idacio® (adalimumab-aacf)
APPROVED BIOSIMILARS
Pfizer November 2019
Sandoz November 2019
Amgen December 2019
Pfizer June 2020
Mylan/Biocon July 2021
Mylan/Biocon July 2020
Amgen December 2020
Biogen September 2021
Eli Lilly December 2021
Coherus December 2021
Amneal March 2022
Amneal April 2022
Amneal May 2022
Coherus August 2022
Fresenius Kabi September 2022
Celltrion September 2022
Fresenius Kabi December 2022
Originator (Manufacturer)
Humira (Abbvie)
Neulasta (Amgen)
Remicade (Janssen)
Neulasta (Amgen)
Lantus® (Sanofi-Aventis)
Humira (Abbvie)
Rituxan (Genentech)
Lucentis® (Genentech)
Lantus (Sanofi)
Humira (Abbvie)
Neupogen (Amgen)
Avastin (Genentech)
Neulasta (Amgen)
Lucentis (Genentech)
Neulasta (Amgen)
Avastin (Genentech)
Humira (Abbvie)
* Abbvie’s adalimumab (Humira) and adalimumab-adaz (Hyrimoz) are approved as 50 mg/mL (with citric acid/citrate) and 100 mg/mL (citratefree) concentrations. All other biosimilars for Humira are approved as 50 mg/mL concentrations only.
† Adalimumab-bwwd (Hadlima) by Organon is also approved as a 100 mg/mL high concentration citrate-free formulation (approved in August 2022). ‡ Pfizer already has Inflectra on the market and has not announced plans to launch Ixifi.
Also available are Eli Lilly’s Basaglar® insulin glargine, a follow-on to Sanofi’s Lantus, and Sanofi’s Admelog® insulin lispro approved as a follow-on to Eli Lilly’s Humalog®
Specialty medications, which include biologics, continue to grow and constitute a large part of drug spend. In the US, it is estimated that biosimilars will cost approximately 15% to 35% less than the originator product, although price dynamics vary. Further, the potential cost savings can vary based on the market segment where brand contracts can play a role. A host of factors will contribute to market acceptability and the potential success of biosimilars. Payers, pharmacies, prescribers, and patients each play an important role in market adoption of biosimilars.
The first biosimilar version of Abbvie’s adalimumab (Humira), adalimumab-atto (Amjevita) became available in the US in January 2023. It is anticipated that multiple Humira biosimilars (including citrate-free and high-concentration formulations) will enter the market in July 2023.
IMMUNOLOGY
adalimumab SC
Celltrion is seeking approval for their investigational biosimilar to Abbvie’s citrate-free, high-concentration (100 mg/mL) Humira. Abbvie’s Humira is a tumor necrosis factor alpha (TNF- α) blocker indicated for the treatment of autoimmune disorders, including rheumatoid arthritis (RA), juvenile idiopathic arthritis (JIA), ankylosing spondylitis (AS), plaque psoriasis (PSO), psoriatic arthritis (PsA), Crohn’s disease (CD) in adults and children, ulcerative colitis (UC), hidradenitis suppurativa (HS), and non-infectious uveitis.
Pfizer is seeking interchangeability of FDA-approved adalimumab-afzb (Abrilada) 50 mg/mL.
FDA APPROVAL TIMELINE
50 mg/mL
• Pfizer (Abrilada) – Pending for interchangeability
100 mg/mL
• Celltrion (Yuflyma) – May 2023
FINANCIAL FORECAST (reported in millions)
Year 2023 2024 2025 2026 2027
Projected Total US Sales $11,480 $7,024 $5,194 $4,134 $3,428
The forecast is a projection of total US sales per year for the branded originator product
OPHTHALMOLOGY
intravitreal
Biocon/Janssen
Biocon/Janssen are seeking approval of their investigational biosimilar (MYL-1701) to Regeneron’s Eylea®, a vascular endothelial growth factor (VEGF) inhibitor indicated for the treatment of neovascular (wet) age-related macular degeneration (AMD), macular edema following retinal vein occlusion (RVO), diabetic macular edema (DME), and diabetic retinopathy (DR).
FDA APPROVAL TIMELINE Pending
FINANCIAL FORECAST (reported in millions)
Year 2023 2024 2025 2026 2027
Projected Total US Sales $6,628 $6,664 $6,126 $5,759 $5,335
The forecast is a projection of total US sales per year for the branded originator product
BIOSIMILAR OVERVIEW continued
ONCOLOGY bevacizumab IV
Bio-Thera Solutions/Sandoz, Centus, and Samsung Bioepis/Organon are seeking approval for their investigational biosimilars to Genentech’s Avastin, a vascular endothelial growth factor (VEGF)-specific angiogenesis inhibitor indicated for the treatment of metastatic colorectal cancer, nonsquamous non-small cell lung cancer, glioblastoma, metastatic renal cell carcinoma (RCC), and recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer.
FDA APPROVAL TIMELINE
• Bio-Thera Solutions/Sandoz (BAT1706) – Pending
• Centus (FKB238) – Pending
• Samsung Bioepis/Organon (Aybintio) – Pending
FINANCIAL FORECAST (reported in millions)
Year 2023 2024 2025 2026 2027
Projected Total US Sales $543 $458 $404 $363 $327
The forecast is a projection of total US sales per year for the branded originator product
ENDOCRINE denosumab SC
Sandoz
Sandoz is seeking approval for their investigational biosimilar (GP2411) to Amgen’s receptor activator of nuclear factor- κB ligand (RANKL) inhibitor denosumab (Prolia®, Xgeva®). Prolia is indicated for the treatment of osteoporosis in men and postmenopausal women, treatment of glucocorticoid-induced osteoporosis in men and women, and to increase bone mass in women receiving adjuvant aromatase inhibitor therapy or men receiving androgen deprivation therapy; all indicated populations are high risk for fracture. Xgeva is indicated for the prevention of skeletal-related events in patients with multiple myeloma and in patients with bone metastases from solid tumors, treatment of select patients with giant cell tumor of bone, and treatment of hypercalcemia of malignancy refractory to bisphosphonate therapy.
FDA APPROVAL TIMELINE
December 6, 2023
FINANCIAL FORECAST (reported in millions)
Year 2023 2024 2025 2026 2027
Projected Total US Sales $4,220 $4,467 $4,329 $3,929 $3,366
The forecast is a projection of total US sales per year for the branded originator product.
BIOSIMILAR OVERVIEW continued
BLOOD MODIFIER
filgrastim IV, SC
Apotex
Apotex is seeking approval of their investigational biosimilar (Grastofil) to Amgen’s Neupogen, a leukocyte growth factor indicated for use in patients with nonmyeloid malignancies who are receiving myelosuppressive anti-cancer drugs; following induction or consolidation chemotherapy for acute myeloid leukemia (AML); with nonmyeloid malignancies in patients who are undergoing myeloablative chemotherapy followed by bone marrow transplantation; to mobilize autologous hematopoietic progenitor cells for collection by leukapheresis; with symptomatic congenital neutropenia‚ cyclic neutropenia‚ or idiopathic neutropenia; and who are acutely exposed to myelosuppressive doses of radiation (hematopoietic syndrome of acute radiation syndrome [HSARS]).
FDA APPROVAL TIMELINE
Pending
FINANCIAL FORECAST (reported in millions)
Year 2023 2024 2025 2026 2027
Projected Total US Sales $71 $63 $56 $51 $47
The forecast is a projection of total US sales per year for the branded originator product.
NEUROLOGY
natalizumab IV
Polypharma/Sandoz
Polypharma/Sandoz are seeking approval for their investigational biosimilar (PB006) to Biogen’s Tysabri®, an integrin receptor antagonist indicated for treatment of multiple sclerosis (MS) and Crohn’s disease (CD).
FDA APPROVAL TIMELINE
May to June 2023
FINANCIAL FORECAST (reported in millions)
Year 2023 2024 2025 2026 2027
Projected Total US Sales $1,079 $1,045 $1,032 $1,023 $951
The forecast is a projection of total US sales per year for the branded originator product
BIOSIMILAR OVERVIEW continued
BLOOD MODIFIER
pegfilgrastim SC
Apotex, Coherus, and Lupin are seeking approval for their investigational biosimilars to Amgen’s Neulasta, a leukocyte growth factor indicated for use in patients with nonmyeloid malignancies who are receiving myelosuppressive anticancer drugs and in patients acutely exposed to myelosuppressive doses of radiation (HSARS).
Coherus is seeking approval of Udenyca OBI®, an investigational biosimilar to Amgen’s Neulasta Onpro®
FDA APPROVAL TIMELINE
• Apotex (Lapelga) – Pending
• Coherus (Udenyca OBI) – October 2023
• Lupin (Lupifil-P) – Pending
FINANCIAL FORECAST (reported in millions)
Year 2023 2024 2025 2026 2027
Projected Total US Sales $622 $420 $347 $283 $234
The forecast is a projection of total US sales per year for the branded originator product
IMMUNOLOGY
ranibizumab intravitreal
Stada Arzneimittel/Xbrane
Stada Arzneimittel/Xbrane are seeking approval for their investigational biosimilar (Ximluci) to Genentech’s Lucentis, a vascular endothelial growth factor (VEGF) inhibitor indicated to treat wet age-related macular degeneration (AMD), macular edema following retinal vein occlusion (RVO), diabetic macular edema (DME), diabetic retinopathy, and myopic choroidal neovascularization (mCNV).
FDA APPROVAL TIMELINE
January to April 2024
FINANCIAL FORECAST (reported in millions)
Year 2023 2024 2025 2026 2027
Projected Total US Sales $752 $505 $361 $275 $223
The forecast is a projection of total US sales per year for the branded originator product
BIOSIMILAR OVERVIEW continued
IMMUNOLOGY
tocilizumab IV, SC
Fresenius Kabi and Biogen/Bio-Thera Solutions are seeking approval for their investigational biosimilars to Genentech’s Actemra®, an interleukin-6 (IL-6) receptor antagonist indicated for the treatment of rheumatoid arthritis (RA), giant cell arteritis, systemic sclerosis-associated interstitial lung disease, polyarticular and systemic juvenile idiopathic arthritis (JIA), and cytokine release syndrome.
FDA APPROVAL TIMELINE
• Fresenius Kabi (MSB11456) – April to June 2023
• Biogen/Bio-Thera Solutions (BIIB800 or BAT1806) – October 9, 2023
FINANCIAL FORECAST (reported in millions)
Year 2023 2024 2025 2026 2027
Projected Total US Sales $1,178 $952 $767 $640 $562
The forecast is a projection of total US sales per year for the branded originator product
ONCOLOGY
trastuzumab IV
Henlius/Accord
Henlius/Accord are seeking approval of their investigational biosimilar (HLX02) to Herceptin, a HER2/neu receptor antagonist indicated for the treatment of HER2-overexpressing breast cancer and HER2-overexpressing metastatic gastric or gastroesophageal junction adenocarcinoma.
FDA APPROVAL TIMELINE
December 15, 2023
FINANCIAL FORECAST (reported in millions)
Year 2023 2024 2025 2026 2027
Projected Total US Sales $418 $357 $317 $286 $259
The forecast is a projection of total US sales per year for the branded originator product
BIOSIMILAR OVERVIEW continued
IMMUNOLOGY
ustekinumab SC
Alvotech
Alvotech is seeking approval for their investigational biosimilar (AVT04) to Janssen’s Stelara, an interleukin 12/23 (IL-12/23) antagonist indicated for the treatment of plaque psoriasis (PSO), psoriatic arthritis (PsA), Crohn’s disease (CD), and ulcerative colitis (UC).
FDA APPROVAL TIMELINE
July to December 2023
FINANCIAL FORECAST (reported in millions)
Year 2023 2024 2025 2026 2027
Projected Total US Sales $6,229 $4,330 $3,042 $2,236 $1,747
The forecast is a projection of total US sales per year for the branded originator product
Keep on Your RADAR
Notable agents that are further from approval have been identified in this unique watch list. These are products with the potential for significant clinical and financial impact. Their development status is being tracked on the MRx Pipeline radar. These pipeline products, their respective class or proposed indication, as well as an estimated financial forecast for the year 2027, are displayed. The financials are projected total annual US sales, reported in millions.
zilucoplan Immunology $313
aficamten Cardiovascular $793
vamorolone
Neurology $306
tabelecleucel Oncology
$401
talquetamab Oncology $135
resmetirom
Cardiovascular
$686
reproxalap
Ophthalmology
$442
giroctocogene fitelparvovec
Hematology/Gene therapy
$131
fidanacogene elaparvovec
Hematology/Gene therapy
$199
aprocitentan
Cardiovascular $66
avacincaptad pegol Ophthalmology $765
bimekizumab Immunology $1,085
blarcamesine
Neurology
$1,049
datopotamab deruxtecan
Oncology
$1,004
exagamglogene autotemcel
Hematology/Gene therapy
$780
Specialty drug names appear in magenta throughout the publication.
Pipeline DRUG LIST
The pipeline drug list is an aerial outline of drugs with anticipated FDA approval through 2024. It is not intended to be a comprehensive inventory of all drugs in the pipeline; emphasis is placed on drugs in high-impact categories. Investigational drugs with a Complete Response Letter (CRL).
APPLICATION SUBMITTED TO THE FDA IN PHASE 3 TRIALS
3
Specialty drug names appear in magenta throughout the publication.
PIPELINE DRUG LIST
Specialty drug names appear in magenta throughout the publication.
Submitted − NDA for OTC use; Priority Review 04/28/2023
− NDA; Orphan Drug; Priority Review 04/30/2023
dengue tetravalent vaccine, live, attenuated
fezolinetant
nalmefene
Submitted − BLA; Fast Track; Priority Review 05/03/2023
Submitted − 505(b)(2) NDA 05/08/2023
cancer (HER2+, unresectable locally advanced or metastatic)
bullosa (dystrophic)
(R/R, ≥ 3rd-line)
fever prevention (ages 4-60 years)
− BLA; Fast Track; Orphan Drug; Priority Review; RMAT 05/19/2023
− BLA; Fast Track; Priority Review 05/22/2023
− 505(b)(2) NDA; Fast Track; Priority Review
nogapendekin alfa inbakicept Immunitybio Bladder cancer (BCG-unresponsive, non-muscle invasive carcinoma in situ, in combination with BCG) Intravesical Submitted − BLA; Breakthrough Therapy; Fast Track 05/23/2023
Invasive pneumococcal disease prevention & related otitis media (ages 6 weeks-17 years) IM Submitted − sBLA; Breakthrough Therapy; Fast Track; Priority Review April 2023
Bristol-Myers Squibb Multiple myeloma (R/R, prior immunomodulatory agent, a proteasome inhibitor, and an antiCD38 monoclonal antibody) IV Submitted − sBLA; Breakthrough Therapy; Orphan Drug 12/16/2023
pembrolizumab (Keytruda) Merck
adalimumab-afzb
50 mg/mL (Abrilada) (biosimilar to Abbvie’s Humira)
Pfizer
norgestrel (Opill®) Perrigo
olaparib (Lynparza®) AstraZeneca
Gastric and gastroesophageal junction adenocarcinoma (locally advanced unresectable or metastatic, 1st-line, in combination with fluoropyrimidine & platinum chemotherapy)
RA; AS; PSO; PsA; JIA; CD; UC SC
Contraception
Prostate cancer (mCRPC, in combination with prednisone ± abiraterone)
Phase 3 (New Drugs)
Oral
Oral
Submitted − sBLA; Orphan Drug 12/16/2023
Submitted − PAS BLA for interchangeability Pending
