While much of the world was on pause during the COVID-19 pandemic, there are definite signs that even a pandemic cannot hold back drug innovation. Despite the variety of challenges posed by the dreaded contagion, the FDA continued to churn out drug approvals in 2021 and innovate health advancements for the American public. Historically, December is the month in which 80% more approvals are rendered than in any other month. This past December was no different as the FDA had over 35 drug approvals to close out the year. These included new molecular entities, new indications, new formulations, first-time generics, and biosimilars. A handful of these approvals have potential for significant impact to both patients and prescribers, as well as payers of healthcare.
Long-Acting Drug Formulations
A leading area of drug innovation continues to be in the development of long-acting drug formulations which are aimed at improving outcomes and providing convenience for patients. Two potential game-changing approvals from December 2021 fall into this category and appear to fill an unmet need within their respective therapeutic classes.
The HIV epidemic continues to be a worldwide problem and a key component of preventing infections is the use of pre-exposure prophylaxis (PrEP) treatments. Multiple published studies have identified oral PrEP adherence as an issue, especially in some categories of patients with the highest risk for infection. In addition, attendance at required follow-up visits and HIV testing after starting treatment is also a well-studied problem identified with oral PrEP therapy.
The first long-acting antiviral for PrEP, Apretude, was approved by the FDA on December 20, 2021. It is administered once every two months to at-risk adults and adolescents to reduce the risk of sexually acquired HIV-1 infection. Apretude’s active ingredient, cabotegravir, was first approved and marketed as Cabenuva in January 2021 to treat HIV as a long-acting therapy.
Setting it apart from other PrEP therapies currently on the market, Apretude is not self-administered and must be given by a health professional resulting in claims on the medical benefit. Currently, Truvada and Descovy, both oral agents taken daily, are the only other FDA-approved therapies for PrEP currently on the market. Data from clinical trials showed that Apretude provided superior protection against HIV compared with daily oral PrEP using Truvada, however no head-to-head trials against Descovy were conducted. Apretude’s “once every 2 months dosing” required to be given by a health professional will likely lead to improved adherence, more frequent testing, and potential for early detection of an HIV infection.
The approximate annual cost of Apretude is $22,200, which does not include the additional clinic fees for administering the injections. Descovy is in the same price range at $23,500 per year. However, Truvada, which is available as a generic, has a much lower cost at just over $300 per year. Pre-exposure prophylaxis (PrEP) therapy is a Grade A recommendation by the U.S. Preventive Services Task Force (USPSTF) requiring Affordable Care Act (ACA)–compliant health plans to provide at least one PrEP option with no out-of-pocket costs. Most PBM and health plan formularies currently prefer generic Truvada. Patients, providers, and payers are challenged with weighing the clinical benefits versus the overall cost when considering the use of Apretude.
Currently, heart disease remains the number one cause of death in the United States and approximately 16 million Americans with clinical atherosclerotic cardiovascular disease (ASCVD) taking statins to lower cholesterol are not at recommended low-density lipoprotein cholesterol (LDL-C) targets. When added to statin therapy, the proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors have been shown to reduce LDL-C between 47% to 60% and have emerged as the best option for patients with the highest risk.
A new inhibitor of PCSK9, Leqvio, was approved December 22, 2021, and joined competitors Praluent and Repatha in this potent therapeutic class. Leqvio is a first-in-class small interfering RNA (siRNA) therapy indicated as an adjunct to diet and maximally tolerated statin therapy for the treatment of adults with heterozygous familial hypercholesterolemia (HeFH) or ASCVD who require additional lowering of LDL-C.
Data from clinical trials revealed that Leqvio, when added to statin therapy, reduced LDL-C by almost 50% compared to placebo. The effect of Leqvio on cardiovascular morbidity and mortality has not been determined, while Praluent and Repatha currently boast this indication. Leqvio must be administered by a healthcare professional which is another differentiator from the self-administered competitors, Praluent and Repatha. Perhaps the most preeminent feature of Leqvio is that it only requires two maintenance doses a year, while Praluent and Repatha must be taken once or twice monthly, depending on the indication.
In the highly rebated PCSK9 inhibitor class, Leqvio is priced similarly to its competitors at around $6,500 per year, with Repatha and Praluent priced annually at $6,561 and $5,850, respectively. The potential for greater adherence to therapy and less needle sticks per year allows Leqvio to emerge with a user-friendly profile that should be appealing to both patients and providers.
Both Apretude and Leqvio are prime examples of continued innovation in today’s pharmaceutical marketplace which is not only focused on improving outcomes but also on minimizing disruptions to the everyday lives of patients. While launching a physician-administered injectable during COVID-19 can present a challenge to market penetration, in-person outpatient visits appear to be rebounding as safety measures have been implemented and the pandemic slows down. It remains to be seen how Apretude and Leqvio will be embraced by patients, prescribers, and payers alike, but both therapies should provide added convenience in therapeutic categories where adherence is integral.
Previously neglected by pharma, a rapidly growing trend in drug innovation has been in the area of orphan drugs which are used for treatment of rare diseases or conditions that affect less than 200,000 persons in the U.S. To help fuel this innovation, the FDA provides incentives such as priority reviews, accelerated approvals and market exclusivity for sponsors to develop products for rare diseases. Typically, these treatments carry a heavy price tag and sometimes questionable clinical benefit.
On December 17, 2021, Oxbryta received an expanded indication approval from the FDA for age extension to patients aged 4 years and older for treatment of sickle cell disease. Oxbryta, a once daily oral treatment, was originally approved by the FDA in 2019 under accelerated approval based on data using a surrogate endpoint. Per the drug’s FDA-approved labeling, continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trial.
Hydroxyurea is considered first line therapy in sickle cell disease, which affects about 100,000 people in the United States. Orphan drugs such as Adakveo, Endari, and Oxbryta are typically added to hydroxyurea treatment. Unfortunately, the very high cost of these newer orphan products has called into question whether they are priced appropriately. Adakveo, given as an intravenous infusion, runs approximately $116k per year, Endari, an oral powder intended to be mixed with food or drink, is close to $45k annually, while the oral tablet Oxbryta tops them all at $127k per year. The Institute for Clinical and Economic Review (ICER) issued a report which indicates the prices of these recently approved add-on treatments for sickle cell disease should be lowered considerably. ICER indicated Adakveo should be priced 70%-74% less, Endari would need to drop by 35%-40% and Oxbryta would need to slash its yearly price by 79% to 83% to meet their established cost-effectiveness standards. As more clinical data becomes available, the cost effectiveness and proven clinical benefit of these agents should continue to be evaluated by payers.
Myasthenia gravis (MG) is an uncommon disorder estimated at 14 to 20 per 100,000 population, which equates to approximately 36,000 to 60,000 cases in the United States. Symptomatic treatment is managed through the use of acetylcholinesterase inhibitors (neostigmine, pyridostigmine) to increase the amount of acetylcholine available at the neuromuscular junction. Vyvgart was approved by the FDA on December 17, 2021 for the treatment of generalized myasthenia gravis (gMG) in adult patients who are anti-acetylcholine receptor (AChR) antibody positive.
Vyvgart is administered as an intravenous infusion once weekly for 4 weeks and subsequent treatment cycles should only be administered based on clinical evaluation. The frequency of maintenance treatment cycles remains to be determined due to lack of adequate trial data. The clinical trial used in the approval was designed to enable an individualized treatment approach with an initial treatment cycle followed by subsequent treatment cycles based on clinical evaluation. How this translates to clinical practice will need to be further explored by the ongoing open-label extension trial currently used to gather longer-term safety and efficacy data.
Currently priced at over $300,000 per year, Vyvgart costs less than half of competitor Soliris, which is priced at $678,392 annually. ICER recently published a report indicating that although both Vyvgart and Soliris appear to significantly improve function and quality of life for gMG patients, however they further stated that the prices for Vyvgart would need to be in the range of $18,300-$28,400 and Soliris lowered to $13,200-$19,400, in order to meet health-benefit cost standards. These cost-benefit concerns and uncertainties about longer-term outcomes for Vyvgart including dosing in real-world settings should be considerations for patients, prescribers, and payers alike.
Drug innovation appears to tote a heavy price tag. Whether those costs are warranted is a question that remains to be answered as we continue to navigate a pandemic which may or may not be close to ending. Payers and pharma are faced with finding middle ground that will provide the best outcomes for utilizers of healthcare without slowing down future innovation.