21 minute read
CLINICAL
Newly approved drugs, gene therapy spark hope ‘An Exciting Time’ to Manage Sickle Cell Disease
Sickle cell disease (SCD) affects approximately 100,000 people living in the United States—double the number of people who have cystic fibrosis and hemophilia combined, according to the CDC. For nearly 20 years, the hematologic disorder had only one treatment option: hydroxyurea.
In the last three years, three new drugs have been approved for SCD, offering the community new hope. The FDA approved two of these drugs at the end of 2019.
“It is truly an exciting time to be caring for SCD patients,” said Deepa caring for SCD patients, said Deepa
From 1989 through 1993, an average of 75,000 hospitalizations due to SCD occurred in the United States, costing approximately $475 million.
Manwani, MD, the direcManwani, MD, the director of pediatric hematology tor of pediatric hematology at the Children’s Hospital at Montefiore, in New York City. “With more treatment options available and in clinical trials, there is great optimism and hope.”
SCD describes a spectrum of disorders, among which sickle cell anemia is the most common. A disease that primarily occurs in people of African and Afro-Caribbean descent, SCD also affects the Latin(x) community, the second largest population in which SCD predominates. SCD also affects people of Middle Eastern, Asian and Mediterranean heritage, according to the American Society of Hematology.
Until recently, hydroxyurea remained the sole treatment for SCD. Approved in 1998 to treat SCD in adults, the myelosuppressive agent originally was developed as an antineoplastic and is used to treat malignancies such as leukemia, ovarian cancer and melanoma. Doctors prescribe hydroxyurea to reduce the occurrence of acute painful episodes, also known as sickle cell crises, a condition caused by irregularly shaped red blood cells aggregating and collecting in blood vessels. Hydroxyurea reduces these painful episodes, which usually require hospitalization, by 50%. While decreasing
hospitalizations helps improve overall quality of life while containing health care systems’ costs, a 50% reduction is not enough, according to John J. Strouse, MD, PhD, an associate professor in the Department of Pediatrics at Duke the Department of Pedia University School of Medicine, in DurUniversity School of Med ham, N.C. “Many people still have emerham, N.C. “Many people s gency department visits and hospitalgency department visits izations for pain when they are taking izations for pain when th hydroxyurea.” hydroxyur
Common side effects Comm include neutropenia, eleinclude ne vated liver enzymes, bone vated liver marrow suppression, marrow anorexia, gastrointesanorexia tinal disturbances tina such as nausea s and vomiting, and infertility. However, Dr. ity Strouse said patients Strouse tend to tolerate the drug relatend to tolerat tively well. tively well.
Newer drugs on the marNewer dru ket give physicians ket g additional tools to additi add to their treatadd t ment arsenal. Despite their potential to improve quality of life for patients with SCD, only time can elucidate the full impact of these noncurative therapies, as long-term outcomes associated with novel therapies have not been studied, Dr. Manwani explained.
In 2017, a branded formulation of L-glutamine (Endari, Emmaus Medical) became the first SCD drug approved in nearly 20 years in 2017, but clinicians have met the drug’s release with mixed reviews. “I think many of us in the SCD community were surprised about Endari’s approval, given some concerns about the data,” Dr. Strouse said.
Among these are an unclear mechanism of action and data demonstrating moderate effectiveness at best. Moreover, some patients find its twicedaily dosing and powder formulation less convenient than swallowing a hydroxyurea pill once a day. L-glutamine also must be taken with food and drink—a feature that creates a barrier for some patients, said Stephanie Guarino, MD, a clinical director of the sickle cell program at Christiana Care’s Center for Special Health Care Needs in Wilmington, Del.
In the fall 2019, the FDA approved crizanlizumab-tmca (Adakveo, Novartis) to treat occlusive crises in patients with SCD aged 16 years and older. The P-selectin blocker prevents platelets, red blood cells and leukocytes from interacting with P-selectin glycoprotein ligand-1 on endothelial cells and platelets. Interfering with the activity of these blood components reduces painful episodes and hospital admissions. Crizanlizumab-tmca can be administered either as monotherapy or concomitantly with hydroxyurea. Common side effects include nausea, pain in the back and joints, and fever.
On Nov. 25, 2019, the FDA approved another drug for SCD—only 10 days after crizanlizumab-tmca’s approval. Voxelotor (Oxbryta, Global Blood Therapeutics) inhibits the polymerization of hemoglobin S, an abnormal form of hemoglobin that causes erythrocytes to sickle. Indidrug costs as creating financial barriers that require a tremendous effort for providers to obtain the insurance authorizations and gain buy-in from hospital committees. She remains optimistic that the benefits these new drugs offer in terms of quality of care and cost will outweigh some of the financial hurdles. Federal interventions such as 340B pricing similar to that offered at federally funded hemophilia treatment centers could help ease some of the payor burden.
cated for patients aged 12 years and older, the oral drug is dosed once daily without regard to food. Like crizanlizumabtmca, it can be taken as monotherapy or adjunctively with hydroxyurea. Headache; gastrointestinal disturbances such as abdominal pain, diarrhea and nausea; and rash, pyrexia and fatigue are among the most common side effects. The drug also requires dose adjustments in patients who have severe hepatic impairment.
Despite the new treatment options, Dr. Strouse does not foresee these new drugs replacing hydroxyurea, given its nearly 20-year history of data, high degree of patient tolerance, and affordability. He anticipates that novel treatments will serve either as options for patients who are unable to tolerate hydroxyurea or as adjunctive therapy.
As with many new drugs, cost is a potential hurdle. At roughly $1,200 per 30-day supply, L-glutamine is the least expensive of the three drugs. Crizanlizumab-tmca requires weight-based dosing. Drug costs are estimated to be approximately $2,500 per vial, not including outpatient clinic use and administration fees. Heavier patients may need up to four vials per treatment. The monthly cost for voxelotor is $10,417. Hydroxyurea costs roughly $1,200 per year on the high end.
Dr. Guarino foresees these high-dollar resistant fetal hemoglobin.
—John J. Strouse, MD, PhD
Gene Therapy Promising
Gene therapy offers some hope to patients who have SCD. According to ClinicalTrials.gov, there are 18 studies on gene therapy for sickle cell either enrolling, actively recruiting or active. Among these are therapies exploring single infusions of CD34+ bone marrow and other CD34+ agents. Another therapy targets BCL11A, a gene that suppresses SCD
According to George Daley, MD, the dean of the faculty of medicine at Harvard Medical School in Cambridge, Mass., newborns express a special form of hemoglobin called fetal hemoglobin. Because fetal hemoglobin does not sickle, babies born with SCD rarely exhibit symptoms initially. However, around the 6-month mark of life, babies stop producing fetal hemoglobin and start producing adult beta globin, due to BCL11A expression. “The data suggest that blocking BCL11A expression might stop cells from sickling,” Dr. Daley said. (Some patients who carry the SCD mutation also have one or more genetic variants for hereditary persistence of fetal hemoglobin [HPFH]. SCD patients who have HPFH were found to have drastically reduced levels of BCL11A and very mild SCD.)
Cost may continue to challenge patients, payors and health care systems alike, but experts agree that better outcomes and potential curative therapies on the horizon offer the SCD community an unprecedented amount of hope.
—Frieda Wiley, PharmD
Dose Optimization Interventions Yield Signifi cant Specialty Drug Cost Savings
Rachel K. Anderson, PharmD
Clinical Program Manager – Clinical Services AllianceRx Walgreens Prime Pittsburgh, Pennsylvania
Specialty medications play a significant role in driving health care costs upward. 1,2 This class of drugs is used by only a small percentage of the population. But because they have high costs and complex management needs, these drugs account for a substantial proportion of overall health care spending. 1
Specialty drug spending is 50% of total drug spending and is forecasted to reach 60% by 2021. 3,4 Formulary management techniques work to drive down expenditures for traditional drugs, but for specialty drugs, it’s a different ball game. As more specialty medications are prescribed, innovative strategies will be needed, and specialty pharmacies and pharmacy benefit managers will play a crucial role in developing and implementing these strategies, saving payors and patients an estimated $250 billion on specialty medications and related nondrug medical costs over the next several years. 5
Utilization Management
Payors have implemented aggressive strategies to manage spending on specialty drugs but still rely on existing utilization management tools to oversee both pharmacy and medical benefits for these drugs. Step therapy and prior authorization pathways are cornerstone approaches to manage total drug spending. Payors also may exclude products from their formularies or negotiate manufacturer rebates to limit costs. Other cost-curbing strategies include split-fill programs, weight-based dose rounding, quantity level limits, and focused site-of-care initiatives.
The goal of these programs is to reduce or eliminate waste. Under a split-fill program, the pharmacy may dispense only a partial supply of certain drugs known to have high discontinuation rates, such as 15 days or less for certain oral oncology products. For weight-based dose rounding, patients prescribed medications with a weightbased dosing protocol receive the most appropriate dose based on their current weight, and the dose is rounded to minimize waste, when applicable. Site-of-care programs focus on transitioning infusion patients from higher cost sites of care, such as acute care settings or hospital outpatient departments, to lower cost sites of care, such as home infusion.
These approaches have been shown to be successful. 1,6,7 For example, one study found that simply shifting the administration site from a hospital outpatient center to physicians’ offices or patients’ homes could cut costs by more than 50%. 1,6
Although these strategies take major steps toward protecting a payor’s bottom line, there still are opportunities to further prevent waste, improve adherence, and reduce overall spending.
Dose Optimization Interventions
One such approach is dose optimization, which minimizes the number of units (oral, injectable, or infused) dispensed for a prescription while providing the same appropriate dose to the patient. For example, some manufacturers charge the same (or very similar) prices for 5- and 10-mg capsules. If a physician writes a prescription for two 5-mg capsules each day, this prescription can be more efficiently and economically dispensed with one 10-mg capsule.
By helping to ensure that dispensing occurs with the most appropriate strength and quantity combination at the lowest possible cost with the fewest number of units for a patient to remember to take, dose optimization improves adherence and creates immediate transactional savings for the payor. 7-9
By implementing dose optimization programs, specialty pharmacies can uncover potential areas of hidden savings. For example, when plans don’t have quantity level limits in place for various specialty drugs, this could result in significant excess cost. Specialty pharmacies are the “last line of defense” in managing the high cost of specialty drugs because they are the last entity to modify a prescription before it is dispensed. In this role, specialty pharmacies work to find and act on opportunities to help reduce the cost of therapy. 9
Not all pharmacy benefit managers
Millions, $
14
12
10
8
6
4
2
No opportunity
Other
Patient preference
Patient not yet stable on dose
No response to outreach
Successful
0
Figure. Estimated annualized savings from specialty medications, Walgreens Study (2019).
Of approximately 500,000 specialty dispenses in 1 year, 45 interventions yielded $4.5 million in actual annualized savings, or an average potential annualized cost savings of $100,000 per prescription.
may be aware of these opportunities, and they may not always have strict quantity limits on all specialty drugs, so this presents potential for significant cost savings. In the specialty pharmacy industry, we often hear that specialty pharmacy must be practiced “one patient at a time,” because one missed intervention opportunity can have significant clinical and financial implications.
Achieved Outcomes
Several studies have looked at achievable drug cost savings for traditional drugs after use of dose optimization programs or stricter quantity level limits. 8,10 One dose optimization pilot program focused on reducing antidepressant spending estimated that a single antidepressant product dose optimization initiative could save approximately $1 million. 10 In another study, data showed that 454 dose optimization interventions (49% of 15 targeted traditional drug categories) over 6 months yielded an estimated annualized drug cost savings of more than $390,000. 8
The unit costs for specialty drugs are higher than for traditional drugs, 11,12 so the potential savings are enormous. Data on dose optimization interventions in specialty are somewhat limited, but recently one specialty pharmacy reported that just 9 dose optimization interventions yielded approximately $135,000 in cost savings that was not specific to the payor or the medication. 13
AllianceRx Walgreens Prime’s dose optimization program yielded almost $13 million in potential annualized cost savings, 7 and that reflected just a small percentage of opportunities.
Currently, AllianceRx Walgreens Prime performs dose optimization on its entire book of business for central fill specialty claims. Commercial plans are the focus, although some Medicare/ Medicaid plans are included. From January 1, 2019, to December 31, 2019, AllianceRx Walgreens Prime’s clinical services team implemented 129 dose optimization interventions related to 460,148 claims (Figure). 7 Of these, 45 interventions (35%) were successful, yielding an estimated annualized drug cost savings of $4,557,856. 7 Of the 80 cases that were not successful, the majority were declined either because the patient was not yet stable on the dose or the prescriber’s office did not respond to outreach attempts. 7 There also were 4 cases that the team identified that involved a dose change or a patient discontinuing therapy before pharmacists were able to intervene. 7
The Pharmacist’s Role
Interventions should not negatively affect the patient—financially or otherwise—and, thus, often require collaboration between the pharmacy and the payor. One hurdle we identified was authorization for split copay overrides from the plan. For example, if the optimized dose requires 2 different strengths to be dispensed, then one of the strengths we would request a copay override so the patient would not be adversely affected financially. Specialty clinicians can work with the payor if a copay override is needed to avoid any additional out-of-pocket cost to the patient.
For drugs with dose optimization opportunities, pharmacists also must consider a patient’s individual treatment plan. When a prescriber initially declines the dose optimization suggestion, the case may be revisited later, depending on the rationale provided (eg, patient is not yet stable on the dose).
Sometimes, interventions also may reduce patients’ out-of-pocket costs. For example, many patients who have copay structures such that they pay a certain percentage (eg, an 80/20 program) may end up paying less out of pocket. The reduced pill burden (eg, taking only 2 pills per day instead of 6) also can make a difference. For example, some patients with a sensitive gag reflex who have difficulty swallowing pills may become more adherent to treatment if they can take fewer pills. Patients always are counseled by a pharmacist about any change in the strength or quantity of the prescription to help them understand how to appropriately take their medication.
Conclusion
A dose optimization program offers an additional way for payors to control rising drug benefit expenditures. 8 Specialty pharmacies are uniquely positioned to serve as a safety net, uncovering and acting on potential opportunities for cost savings. For pharmacy programs in any setting to be successful, they must be able to better manage rising drug costs without compromising quality of care for patients. 8
References
1. Hirsch BR, Balu S, Schulman KA. The impact of specialty pharmaceuticals as drivers of health care costs. Health Affairs. 2014;33(10):1714-1720.
2. Lotvin AM, Shrank WH, Singh SC, et al. Specialty medications: traditional and novel tools can address rising spending on these costly drugs. Health Affairs. 2014;33(10):1736-1744.
3. Prime Therapeutics. The inevitable increase in specialty growth. November 14, 2017. bit. ly/3fAo2gX. Accessed May 8, 2020.
4. Pharmacy Benefit Management Institute. 2019 Trends in specialty drug benefits. bit.ly/3dwc7ii. Accessed May 8, 2020.
5. Namovicz-Peat S, Trompeter E, eds. Specialty Pharmacy Trends and Strategies: 2015. 8th ed. Atlantic Information Services; 2015.
6. Vora JB. Milliman white paper. Evaluation of medical specialty medications: utilization and management opportunities. April 8, 2014. bit.ly/2yEvUgV. Accessed May 5, 2020.
7. Data on file. AllianceRx Walgreens Prime; 2020.
8. Calabrese DC. Dose-optimization intervention yields significant drug cost savings. J Managed Care Pharm. 2002;8(2):146-151.
9. SPCMA.org. The management of specialty drugs. bit.ly/2WCL0vs. Accessed May 8, 2020.
10. F-D-C Reports. The Pink Sheet. 2001;63(18):27-28.
11. Elsevier. Managing the costs of specialty drugs. 2017. bit.ly/35KkwMC. Accessed May 5, 2020.
12. Prime Therapeutics. Focus on trend. Spring 2018. bit.ly/2WgA33K. Accessed May 5, 2020.
A generic waiting in the wings could be a cost-saver New Entrants Expand PrEP Options for HIV
Managed care pharmacists and other stakeholders interested in expanded treatment options for HIV pre-exposure prophylaxis (PrEP) have some new choices, including a pending generic formulation that may offer some savings. But infectious disease experts noted that several market barriers remain, not the least of which is acceptance by health care policymakers and clinicians.
Since 2012, emtricitabine-tenofovir disoproxil fumarate (FTC/TDF; Truvada, Gilead), which had annual sales of about $3 billion, has been the only PrEP available. Last year, the FDA approved FTC-tenofovir alafenamide (FTC/TAF; Descovy, Gilead) for PrEP, but it is not indicated for cisgender women, who are at risk from receptive vaginal sex.
Delivering more than products to specialty pharmacies
Through our Cardinal Health Specialty Pharmaceutical Distribution (SPD) business, we work with your specialty pharmacy to identify your unique challenges, generate insights, and deliver the products, technologies and knowledge you need.
Your commitment to care for your patients is unrivaled. We’re proud to be with you every step of the way with a broad specialty product portfolio, emergency ordering and consignment inventory options.
For more information, call 866.677.4844 or visit cardinalhealth.com/spd-specialtypharmacy
Also, a generic version of FTC/TDF by Teva Pharmaceuticals is expected this fall.
“The looming question is how often patients and providers use the generic version for HIV treatment and prevention,” said Rochelle Walensky, MD, MPH, the chief of infectious diseases at Massachusetts General Hospital, in Boston.
An estimated 90% of patients who were taking FTC/TDF have switched to Descovy for treatment. “However, the jury is still out as to how many patients will be switched to Descovy for prevention, especially with the availability of generic Truvada,” she said.
Gilead reportedly has priced the brand-name versions the same and is marketing FTC/TAF as a safer option. “Although the trials demonstrated that Descovy has slightly better biomarkers of renal and bone safety over Truvada, it is not clear if these translate into clinically meaningful differences in adverse events,” Dr. Walensky said, noting that early studies suggest increased weight gain and cardiovascular risk factors with FTC/TAF.
The initial FTC/TAF trial had surrogate markers for bone mineral density and renal toxicity, “but not true meaningful end points,” Dr. Walensky said. “Nonetheless, for patients with HIV who are aging and might have comorbidities, there might be an indication for some of those patients to change from Truvada to Descovy.”
Will the Generic Be Accepted?
As for clinicians embracing the generic PrEP medication, “providers do not generally revert to a previous drug because of costs and costs alone,” Dr. Walensky said. “Thus, it is not entirely clear once Truvada goes off patent and can be acquired much cheaper, how many practitioners will actually prescribe the generic version and how many patients will consider a switch.”
Regardless, Dr. Walensky acknowledged the clever marketing by Gilead. “I also believe it is an intentional move to dissuade clinicians from using generic Truvada,” she said. “There are published data about Descovy dating back to 2001.”
With more than 1 million people in the United States needing PrEP, public health interventions need to consider “whether putting people on a more expensive drug like Descovy versus generic Truvada will result in fewer people having access to PrEP, especially since we do not really understand or know the end game of Descovy’s safety profile,” she said.
Meanwhile in January, the New York City Department of Public Health and Mental Hygiene announced that its drug of choice for PrEP would remain FTC/TDF. “So I think there are numerous policymakers who understand these implications, despite the marketing efforts by Gilead,” Dr. Walensky said.
A Pharmacist’s Perspective
Although FTC/TAF is considered safer for kidney and bone problems, “there may be some cardiovascular concerns with the newer drug,” said Rodrigo Burgos, PharmD, a clinical assistant professor in the Section of Infectious Diseases Pharmacotherapy at the University of Illinois at Chicago College of Pharmacy. “Hence, at this stage, I do not believe we can definitively rule out using Truvada for PrEP.”
Until it is proven that FTC/TAF is more cost-effective than FTC/TDF for PrEP, “it is easy to understand why an entity would prefer to use the less costly option of Truvada,” Dr. Burgos said.
Similarly, because evidence of efficacy for FTC/TAF as PrEP is limited to specific populations such as men who have sex with men, “having a single agent that is effective in all populations may add appeal to Truvada when making decisions on cost and public health,” Dr. Burgos pointed out.
He said generic FTC/TDF will be embraced by both patients and physicians. “Most patients do not like to change the medications on which they have been stable, specifically to a generic version,” he said. “However, any dislike is usually momentary and has not been an issue in the past when many other antiretrovirals have gone generic.”
On the other hand, FTC/TAF may provide a safer treatment option for some patients, he noted, again citing the issue of kidney disease and bone disorders. “Availability of safer medications is a win-win for both patients and health care providers, and should be the goal for every medication on the market.”
Dr. Burgos said he does not find it odd or suspect that Gilead is introducing a new drug for PrEP within one year of FTC/TDF becoming generic. “It is not uncommon for a company to introduce newer and better products around patent expiration of a product.”
However, other people have taken exception to Gilead’s products. The federal government sued Gilead, seeking damages claiming infringement of its patents related to PrEP and that the company profited from research funded by taxpayers. There also is a patient-driven class action lawsuit against Gilead, claiming that it knowingly sold a product (FTC/TDF) that caused bone and kidney issues when it had a safer alternative (FTC/TAF) that it did not seek approval for until its patent was expiring.
Big Challenges Ahead
The biggest challenge with any other PrEP agent, regardless of whether it is a brand-name or generic medication, “is identifying and reaching out to at-risk individuals and making PrEP available to them,” Dr. Burgos said. “Will the lower cost of generic Truvada actually translate to savings for society or extra services for our patients, or will only a handful of people benefit from that lower cost?” —Bob Kronemyer
Dr. Walensky reported no relevant fi nancial relationships. Dr. Burgos reported working on trials sponsored by GlaxoSmithKline and Merck.
Unit Dose, Bar Coding, Pharmacy & Nursing Supply Experts! ® ® Medi-Dose EPS EPS ® ...THE RIGHT PRESCRIPTION FOR PHARMACISTS
High quality, safe and effective products for medication administration, preparation and dispensing...in stock for fast shipment worldwide.
Priced low and ready to go!
U Medi-Dose ® Solid Oral Unit Dose Packaging
U TampAlerT ® Liquid Unit Dose Packaging
U MILT ® Software for Medication Identification
and Bar Coding
U LiquiDose ® Labels
U IV Additive Disposable Accessories
U Steri-Dropper ® Sterile Ophthalmic
Dropper Bottles U Compounding Products
U Cleanroom Supplies
U Ophthalmic Practice Accessories
U Resealable and Ultraviolet Inhibitant Bags
U Tamper-Evident Products
U Bottles, Vials and Containers
U Operating and Procedure Room Accessories
U ShrinkSafe ® Bands and Safety Products
U Tapes and Labels U Maternity and Laboratory Products U Record Keeping and Identification Products U Storage and Transport Products
Visit our website for our EZ order system!
EPS ® Exceptional Products and Service A Member of The Medi-Dose ® Group
