16 minute read
approvals
Specialty spending ekes out a win over traditional meds
2021 New Drug Approvals: A Year of Firsts
Aurora, Colo.—Two of the most notable new drug approvals in 2021 were not technically new; they were new indications, but they should have a significant effect on the specialty market. Two biosimilars became the first interchangeable biologics approved by the FDA.
Just more than one year after it was approved, insulin glargine-yfgn (Semglee, Viatris/Biocon Biologics) was granted interchangeable status with its reference product Lantus (Sanofi) in July 2021. It can be automatically substituted with the reference product by a pharmacist, similar to the substitutions made for traditional generics. On Oct. 20, Express Scripts listed insulin glargine-yfgn as a preferred insulin on its National Preferred Formulary, due to take effect in January 2022.
“Semglee currently costs about half as much as Lantus,” explained Aimee Tharaldson, PharmD, at the 2021 AMCP Nexus meeting. “This could save clients $20 million next year due to this decision,” added Dr. Tharaldson, a senior clinical pharmacist of Emerging Therapeutics at Express Scripts.
The second biosimilar to be designated as interchangeable is adalimumabadbm (Cyltezo, Boehringer Ingelheim), a biosimilar to Humira (AbbVie). Adalimumab-adbm, which was originally approved in August 2017, was made interchangeable on Oct. 18. Unlike insulin glargine-yfgn, however, adalimumabadbm will not launch immediately due to patent settlement agreements with AbbVie. It will launch in 2023, along with five other biosimilars to adalimumab, but only adalimumab-adbm has interchangeability at this point.
Another biosimilar approved this year, ranibizumab-nuna (Byooviz, Samsung Bioepis/Biogen), a biosimilar to Lucentis (Genentech), is the first ophthalmic biosimilar. The anti–vascular endothelial growth factor therapy was approved to treat several eye conditions, including neovascular age-related macular degeneration, the leading cause of blindness in those 65 years of age and older.
Bevacizumab (Biothera), a biosimilar to Avastin (Genentech) for several cancer types, and another adalimumab biosimilar by Coherus were expecting approvals before the end of the year.
“So far, FDA has approved 31 biosimilars to 11 biologics. And 21 biosimilars to 8 biologics are currently available on the market,” Dr. Tharaldson explained. “These biosimilars have combined sales of about $4 billion.”
Specialty spending, which has been creeping up each year, has overtaken the traditional drug spend, Dr. Tharaldson noted. “Fifty-one percent of per member per year drug spend under the pharmacy benefit is for specialty drugs,” she said, but only about 2% of the patients covered take specialty medications.
More Firsts
Long-Acting HIV Medication
ViiV Healthcare kicked off the year with the approval of the first long-acting HIV medication. Cabotegravir-rilpivirine injectable (CAB/RPV; Cabenuva) is an alternative to oral treatment for adults with low viral loads who are on a current stable regimen and no history of treatment failure, she explained. Dosed monthly, CAB/RPV comes as a copack with two injectable medications, ViiV’s cabotegravir and Janssen’s rilpivirine.
The approval was based on the phase 3 ATLAS and FLAIR studies that included more than 1,100 patients from 16 countries. Prior to initiating treatment, oral dosing of CAB and RPV are given to assess tolerability with therapies.
The first therapy for adults with active lupus nephritis was also approved in January. Lupus nephritis, a common complication of systemic lupus erythematosus, causes irreversible kidney damage and significantly increases the risk for kidney failure, cardiac events and death. Voclosporin (Lupkynis, Aurinia), an oral therapy used with a background immunosuppressive regimen, is a calcineurin inhibitor. In the pivotal AURORA trials, patients treated with voclosporin with immunosuppressives were more than twice as likely to achieve renal response and experience a decline in the urine protein to creatinine ratio.
“For years, treating patients with lupus nephritis has been challenging. We have had a very limited number of therapeutic options, and these have been only modestly effective but highly toxic,” Brad H. Rovin, MD, the director of the Division of Nephrology at The Ohio State University Wexner Medical Center, in Columbus, and an AURORA clinical trial investigator, said in a press release announcing the approval (bit.ly/30ekHkz).
“About 10% of these patients with lupus nephritis develop end-stage renal disease,” Dr. Tharaldson said.
Genetic Disorders
Casimersen (Amondys 45, Sarepta Therapeutics) is the first drug approved to treat Duchenne muscular dystrophy (DMD) with a mutation amenable to exon 45 skipping. About 10,000 boys and young men have DMD, but only about
8% have this genetic mutation, according to Dr. Tharaldson. Casimersen is an antisense oligonucleotide that skips over exon 45 to enable a partially functioning dystrophin protein. The medication is given as a weekly infusion. The new indication is based on a statistically significant increase in dystrophin production in skeletal muscle observed in patients treated with casimersen, which is reasonably likely to predict clinical benefit.
Fosdenopterin (Nulibry, BridgeBio/ Origin Biosciences) is the first drug for patients with molybdenum cofactor deficiency (MoCD) type A, which affects fewer than 150 infants and young children worldwide. MoCD type A is an autosomal recessive, inborn error of metabolism caused by mutations in the molybdenum cofactor synthesis 1 gene and characterized by a deficiency in molybdenum cofactor production and enzyme activity. The lack of activity leads to a buildup of sulfite and secondary metabolites in the brain, which causes irreversible, progressive neurologic damage.
“Nulibry allows the production of a missing enzyme that reduces the buildup of the harmful substances in the brain. It’s administered as a daily IV infusion,” Dr. Tharaldson said. Small studies showed improved overall survival (OS) compared with an untreated cohort.
Belzutifan (Welireg, Merck), an oral hypoxia-inducible factor-2 alpha (HIF2alpha) inhibitor, is the first treatment for von Hippel-Lindau (VHL) syndrome, a rare genetic disorder that leads to the development of cancerous and noncancerous tumors. Seventy percent of people with this condition develop renal cell carcinoma, Dr. Tharaldson explained. Belzutifan reduces transcription and expression of HIF-2alpha target genes associated with cellular proliferation, angiogenesis and tumor growth.
“In Study 004, nearly half of all patients with VHL-associated renal cell carcinoma, as well as the majority of patients with VHL-associated central nervous system hemangioblastomas or pancreatic neuroendocrine tumors, who were treated with Welireg experienced a reduction of their respective tumor size,” explained Ramaprasad Srinivasan, MD, PhD, the head of the Molecular Cancer Therapeutics Section, National Cancer Institute.
Cancer Drugs Approved
Non-small cell lung cancer
Non-small cell lung cancer (NSCLC) patients also benefited from several approvals. Although lung cancer rates are decreasing in the United States, 235,760 adults still are diagnosed each year, and 85% with NSCLC, according to the American Society of Clinical Oncology. • Sotorasib (Lumakras, Amgen) is the first targeted treatment for KRAS
G12C mutated locally advanced or metastatic NSCLC. About 13% of
NSCLC patients have this “previously elusive mutation,” according to
David M. Reese, MD, the executive vice president of Research and Development at Amgen. A phase 2 study found a 37% objective response rate. • Mobocertinib (Exkivity, Takeda) is the first medication to target epidermal growth factor receptor (EGFR) exon 20 insertion mutations, and is indicated for locally advanced or metastatic
Non-small cell lung cancer (NSCLC) patients benefited from several approvals in 2021, with drugs hitting a variety of targets, including KRAS G12C, epidermal growth factor receptor exon 20 insertion mutations and METexon14 alterations. Although lung cancer rates are decreasing in the United States, 235,760 adults still are diagnosed each year, 85% of whom have NSCLC, according to the American Society of Clinical Oncology. lib ll h d i f
2021 APPROVALS
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disease. “EGFR exon 20 insertion plus
NSCLC is an underserved cancer that we have been unable to target effectively with traditional EGFR TKIs [tyrosine kinase inhibitors],” said Pasi
A. Jänne, MD, PhD, of the Dana Farber
Cancer Institute, in Boston. • Amivantamab-vmjw (Rybrevant, Janssen), an EGFR exon 20–directed and mesenchymal–epithelial transition (MET) receptor–directed antibody, was approved to treat patients with
NSCLC with EGFR exon 20 insertion mutations. “This [NSCLC variant] is pretty rare,” Dr. Tharaldson said.
“Only about 1% to 2% of patients with
NSCLC have these exon 20 insertion mutations. It’s more common in Asian populations and is associated with lower survival rates.” • Tepotinib (Tepmetko, EMD Serono), a second oral MET inhibitor, is indicated for adults with NSCLC that has metastasized and has MET exon 14 alterations, which affects about 3% to 4% of patients with NSCLC. • Trilaciclib (Cosela, G1 Therapeutics/
Boehringer Ingelheim), a cyclindependent kinase 4 and 6 inhibitor, was approved to reduce chemotherapyinduced myelosuppression in extensive-stage small cell lung cancer. The
IV infusion is given four hours before chemotherapy to reduce the duration and severity of neutropenia.
Lymphomas
Lymphomas also benefited from new options in 2021. • Loncastuximab tesirine-lpyl (Zynlonta,
ADC Therapeutics) is the first CD19directed antibody and alkylating agent conjugate approved for diffuse large
B-cell lymphoma (DLBCL) and indicated in the third-line setting. DLBCL affects about 10% of patients. • Lisocabtagene maraleucel (Breyanzi,
Bristol Myers Squibb [BMS]), a chimeric antigen receptor (CAR) T-cell agent, was approved for the third-line treatment of adults with relapsed/ refractory DLBCL. It is given as a one-time infusion. • Umbralisib (Ukoniq, TG Therapeutics) is an oral phosphoinositide 3-kinase delta and casein kinase 1 epsilon inhibitor approved for adults with relapsed/refractory marginal zone or follicular lymphoma. Marginal zone lymphoma is diagnosed in about 7,500
U.S. patients and follicular lymphoma in about 15,000. Both are slow-growing forms of non-Hodgkin lymphoma,
Dr. Tharaldson explained. both for relapsed/refractory disease: melphalan flufenamide (Peptaxo, Oncopeptides), a peptide–drug conjugate alkylating drug used in combination with dexamethasone, and idecabtagene vicleucel (Abecma, BMS/bluebird bio), a B-cell maturation antigen-directed CAR T-cell therapy. However, Oncopeptides is withdrawing melphalan flufenamide after results from the OCEAN study (ClinicalTrials.gov Identifier: NCT03151811) showed the OS of patients who received the injection with dexamethasone was lower than those who were treated with pomalidomide (Pomalyst, BMS) and dexamethasone, as reported in Pharmacy
Practice News (bit.ly/3oh6xHO). Collaborating with the FDA, Oncopeptides will ensure that patients who need to keep using melphalan flufenamide will have access to it. (For more information, contact OnCourse Patient Support Services at 1-844-300-6626.)
“Even though there are a lot of drugs to treat MM, most patients wind up relapsing,” Dr. Tharaldson said.
Advanced Renal Cell Carcinoma
The FDA approved tivozanib (Fotivda, Aveo Oncology), a new oral angiogenesis inhibitor, for third-line treatment of adults with advanced renal cell carcinoma. “About of 76,000 new cases of kidney cancer are diagnosed each year, and about 90% are renal cell carcinoma, which typically does not respond well to chemotherapy,” she explained.
Cholangiocarcinoma
Infigratinib (Truseltiq, BridgeBio/ Helsinn) is an oral fibroblast growth factor 2 TKI indicated for cholangiocarcinoma that is inoperable. About 8,000 cases of cholangiocarcinoma are diagnosed each year. It’s typically difficult to diagnose, and the average survival rate is less than 10%. About 50% of cases involved an FGFR2 mutation.
Leukemias
Asparaginase erwinia chrysanthemi (recombinant)-rywn (Rylaze, Jazz Pharmaceuticals) is a new asparaginespecific enzyme product used with other chemotherapy drugs to treat acute lymphoblastic leukemia (ALL) or lymphoblastic lymphoma (LBL) for patients 1 month of age and older. “These are rare cancer types that primarily affect children,” Dr. Tharaldson said.
Clinical data from an ongoing pivotal phase 2/3, single-arm, open-label, multicenter, dose-confirmation study evaluating pediatric and adult patients with ALL or LBL demonstrated the achievement and maintenance of nadir serum asparaginase activity (NSAA) greater than or equal to 0.1 U/mL at 48 hours using intramuscular 25-mg/m2 doses of asparaginase erwinia-rywn. The proportion of patients maintaining NSAA of at least 0.1 U/mL at 48 hours after a dose of asparaginase erwinia-rywn was 93.6% (95% CI, 92.6%-94.6%).
Asciminib (Scemblix, Novartis) was approved to treat Philadelphia chromosome–positive myeloid leukemia
chronic phase (Ph+ CML-CP) previously treated with two or more TKIs, and Ph+ CML-CP with the a T315I mutation. Asciminib is the first FDAapproved CML treatment that works by binding to the ABL myristoyl pocket.
Cervical cancer
Tisotumab vedotin-tftv (Tivdak, Seagen/Genmab) is an antibody inhibitor conjugate approved to treat women with recurrent or metastatic cervical cancer with progression on or after chemotherapy.
Orphan and Other Conditions
Belumosudil (Rezurock, Kadmon Holdings) is an oral graft inhibitor for patients 12 years of age and older with chronic graft-versus-host disease (cGVHD), a common complication after hematopoietic stem cell transplant.
In ROCKstar, a randomized, openlabel, multicenter pivotal trial of belumosudil, patients with cGVHD who had received two to five prior lines of systemic therapy achieved an overall response rate of 75% through cycle 7 on day 1 of treatment, with 6% achieving a complete response and 69% achieving a partial response. The median time to first response was 1.8 months.
“Patients receiving Rezurock reported significant improvements in cGVHD symptoms, showing that not only did treatment result in organ responses, but it also made people feel better. This is so important for a chronic disease with a high symptom burden,” Stephanie Lee, MD, MPH, a professor at the Fred Hutchinson Cancer Research Center and the University of Washington School of Medicine, in Seattle, said in a Kadmon Holdings press release announcing the approval (bit.ly/3qyeH1m).
Other notable approvals include two ileal bile acid transporter inhibitors: odevixibat (Bylvay, Albireo Pharma) and maralixibat (Livmarli, Mirum). Odevixibat is indicated for the once-daily oral treatment of pruritus associated with progressive familial intrahepatic cholestasis patients 3 months of age and older. Maralixibat is approved for cholestatic pruritus caused by Alagille syndrome.
Pegcetacoplan (Empaveli, Apellis Pharmaceuticals) is the first C3 complement inhibitor used to treat paroxysmal nocturnal hemoglobinuria, a rare life-threatening blood disorder affecting about 6,000 patients in the United States.
The approval of pegcetacoplan is based on results from the head-to-head phase 3 PEGASUS study, which demonstrated superiority to eculizumab (Soliris, Alexion) for the change from baseline in hemoglobin level at week 16, with an adjusted mean increase of 3.84 g/dL of hemoglobin (P<0.0001). Eighty-five percent of pegcetacoplan patients were transfusion-free over 16 weeks versus 15% of those treated with eculizumab (Solirus, Alexion).
Aducanumab (Aduhelm, Biogen/ Eisai), an amyloid beta–directed antibody indicated to treat Alzheimer’s disease, was probably one of the most controversial approvals (https://bit. ly/3bWL3du-PPN). “The results of clinical trials are mixed,” Dr. Tharaldson said. “Two phase 3 trials were actually stopped early because they didn’t look like they’re going to be effective. But a reanalysis of one of the studies found that those treated longer term with a higher dose responded to therapy.”
Avalglucosidase alfa-ngpt (Nexviazyme, Sanofi Genzyme) is an acid alphaglucosidase (GAA) enzyme replacement therapy for people 12 months of age and older with Pompe disease, which is caused by a genetic deficiency or dysfunction of the lysosomal enzyme GAA, which results in a buildup of glycogen in muscle cells throughout the body. The accumulation of glycogen leads to irreversible damage to the muscles, including the diaphragm that supports respiratory function and skeletal muscles that affect mobility, functional endurance and breathing.
About 3,500 people suffer from Pompe disease. Avalglucosidase alfa-ngpt is an enzyme replacement therapy that targets the mannose-6-phosphate receptor, which ameliorates cellular enzyme uptake and enhances glycogen clearance, improving respiratory function and walking distance.
—Aimee Tharaldson, PharmD
—Marie Rosenthal
Dr. Tharaldson reported no relevant fi nancial disclosures. In addition to her presentation at AMCP Nexus, company and FDA press materials were used to develop this article. This is not a comprehensive list of all specialty drugs approved in 2021.
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