AscellaHealth Report Drills Down on Specialty Drug Launches
Reprinted with AIS Health permission from the February 2025 issue of Radar on Specialty Pharmacy
Krystal Biotech, Inc.’s Vyjuvek (beremagene geperpavec-svdt) soon may have a gene therapy competitor, and the FDA could approve the first biosimilar of Roche Group member Genentech USA, Inc. and Novartis Pharmaceuticals Corp.’s Xolair (omalizumab) shortly. That's according to AscellaHealth LLC’s latest breakdown of insights into new, pending and upcoming launches in specialty and rare disease, biosimilars and cell and gene therapies (CGTs).
AscellaHealth partners with life sciences companies to offer customizable solutions to support the specialty pharmaceutical industry. Its Specialty and Rare Pipeline Digest: Q4 2024 takes an expansive look at the specialty industry, from the launches of the biosimilars of Stelara (ustekinumab) from Johnson & Johnson Innovative Medicine to the new atopic dermatitis indication for Galderma Laboratories, L.P.’s Nemluvio (nemolizumab-ilto).
AIS Health, a division of MMIT, spoke with Andy Szczotka, Pharm.D., chief pharmacy officer at AscellaHealth, about some of the report’s findings. (Editor’s note: These comments have been edited for length and clarity.)
AIS Health: Which recently approved specialty drugs hold the most promise and why?
Szczotka: Three of the most recently approved specialty drug products that hold the potential to influence their respective therapeutic markets are:
Attruby (acoramidis) [from BridgeBio Pharma, Inc.] is the second approved selective stabilizer of transthyretin (TTR) for the treatment of adult patients with cardiomyopathy of wild-type or variant transthyretin-mediated amyloidosis (ATTR-CM) to reduce cardiovascular death and cardiovascular-related hospitalization. Attruby will compete directly with Pfizer's Vyndaqel (tafamidis meglumine) and Vyndamax (tafamidis), which were both approved in 2019 for ATTR-CM. All three products share the same mechanism of action as selective stabilizers of TTR; however, Attruby is priced lower than the tafamidis products. [Vyndaqel and Vyndamax are around $268,000, and Attruby is around $244,500.] In the near future, Attruby will likely compete with Alnylam's Amvuttra (vutrisiran) [around $463,500] and AstraZeneca/Ionis' Wainua (eplontersen) [around $499,000], which are both being evaluated for ATTR-CM with potential approvals in early 2025 and 2026, respectively. Amvuttra and Wainua are differentiated in their mechanism of action as TTR silencers and are currently approved for use in ATTR-PN at a significantly higher price point.
Itovebi (inavolisib) [from Roche Group member Genentech USA, Inc.] is an oral phosphatidylinositol 3-kinase inhibitor indicated in combination with palbociclib and fulvestrant for the treatment of adults with endocrine-resistant, PIK3CA-mutated, hormone receptor-positive, HER2-negative, locally advanced or metastatic breast cancer, as detected by an FDA-approved test following recurrence on or after completing adjuvant endocrine therapy. This triple therapy combination provides another option for the treatment of breast cancer and has shown a doubling of the median progression-free survival, objective response rate and the duration of response compared to the double therapy and appears to be better tolerated than alpelisib [Novartis Pharmaceuticals Corp.’s Vijoice], another PI3K inhibitor (e.g., 12% grade 3 hyperglycemia vs. 32.7%).
Crenessity (crinecerfont) [from Neurocrine Biosciences, Inc.] is an oral nonsteroidal treatment approved in December 2024 to reduce the mean daily glucocorticoid dose in people with congenital adrenal hyperplasia. Patients with this disease require high doses of glucocorticoids (more than is typically needed to replace the deficient cortisol) because the glucocorticoids also help to reduce the excess levels of androgens. Crenessity works by reducing excessive adrenal androgen production, which helps reduce the amount of glucocorticoid treatment needed. Clinical studies demonstrated an 18% to 27% reduction in the daily glucocorticoid dosing, which will help with the side effects and complications of treatment with long-term, high-dose steroids.
AIS Health: Do any of the recently approved agents potentially pose a challenge for health plan coverage and why?
Szczotka: Four of the most recently approved specialty drug products that may create coverage issues for payers include:
Hympavzi (marstacimab-hncq) [from Pfizer Inc.] and Alhemo (concizumab-mtci) [from Novo Nordisk] are both newly approved hemophilia A and B therapies. Hympavzi is a once-weekly subcutaneous injection for the treatment of adults and pediatric patients 12 years of age and older with hemophilia A without inhibitors or hemophilia B without inhibitors. Hympavzi is a monoclonal antibody that works by reducing activity of an anticoagulatory protein called tissue factor pathway inhibitor. It is the first U.S.-approved treatment for hemophilia to be administered with a prefilled auto-injector pen and designed to be a convenient alternative to periodic infusions of proteins that boost blood clotting. Alhemo is the second tissue factor pathway inhibitor (TFPI) antagonist to prevent or reduce the frequency of bleeding episodes in hemophilia A with inhibitors or hemophilia B with inhibitors. Alhemo is also dosed subcutaneously via a single-patient-use prefilled pen but is dosed daily rather than weekly. Decisions for expanded indications for use of both of these products with and without inhibitors are due in later 2025. In the hemophilia A space, both products will compete with short half-life (SHL) and extended half-life (EHL) FVIII products as well as Hemlibra, and it will compete with SHL and EHL FIX products in the hemophilia B space. It is priced at a premium to Hemlibra [which is about $560,000] and the SHL and EHL factor products with the prefilled pen delivery option.
Cobenfy (trospium chloride; xanomeline tartrate) [from Bristol Myers Squibb] is an oral, first-in-class, muscarinic agonist for the treatment of schizophrenia in adults that works via a different mechanism of action than other agents used for this disease. It selectively targets M1 and M4 receptors in the brain, without blocking D2 receptors. In indirect trial comparisons, the main advantage for Cobenfy is having fewer side effects (e.g., weight gain, pacing and drowsiness) than current therapies but is dosed twice daily. But [it] does not have long-term clinical studies demonstrating sustained efficacy and reduction of adverse effects and comes at a much higher cost [about $22,500 annually] than current standards of care.
Aqneursa (levacetylleucine) [from IntraBio] and Miplyffa (arimoclomol) [from Zevra Therapeutics] are the first two approved therapies for the treatment of Niemann-Pick disease type C (NPC). While these agents work via different mechanisms of action, both agents demonstrated functional improvements in neurologic conditions on different rating scales for patients. These improvements, while moderate on the various rating scales, slowed disease progression for these patients. However, the cost of these therapies is ultra expensive ($700,000 to $1,000,000 per year), and long-term effectiveness and safety in halting further disease progression or preventing end organ damage or use as combination therapy are not yet known.
AIS Health: The report mentions the approval of Attruby. It seems like there has been a big focus on developing drugs to treat transthyretin-mediated amyloidosis. Why is that?
Szczotka: Transthyretin amyloid cardiomyopathy is an underdiagnosed and potentially fatal disease of the heart muscle. Prior to the approval of Attruby, treatment of ATTR-CM consisted of conventional heart failure medications and the TTR stabilizer, tafamidis (Vyndamax and Vyndaqel). In 2023, the tafamidis products had over $3.3 billion in sales and was the only product approved specifically for the treatment of ATTR-CM. With the approval of Attruby, this will provide additional competition in this market. Additionally, two other products with a different mechanism of action, TTR silencers, currently approved for ATTR-PN, Amvuttra (vutrisiran) and Wainua (eplontersen), will be undergoing FDA review for ATTR-CM in 2025 and 2026. If approved, this will provide additional therapy options for this medical condition.
AIS Health: Genentech's Ocrevus (ocrelizumab) and Bristol Myers Squibb's Opdivo (nivolumab) are the most recent intravenous infusibles to gain FDA approval for subcutaneous formulations. What are benefits of the subcutaneous formulations and to whom? What are benefits of the IV formulations and to whom?
Szczotka: The subcutaneous route of administration offers many benefits for patients, physicians and payers. The benefits include the flexibility to receive treatment where it is best for patients and their providers, reduction in the steps required for medication preparation and time needed for administration, assistance with infusion chair availability and capacity, potentially avoid port placement and assist patients that may have difficulty in accessing a vein, potential increased mobility due to the freedom of burden from IV or infusion pumps, as well as cost-saving benefits.
Some potential advantages of IV administration include the ability to provide precise medication dosing along with potentially faster onset of action of the medication, lower out-of-pocket cost for patients due to their medical benefit design and a higher degree of access and interaction to health care professionals and other patients.
AIS Health: Do any of the drugs with upcoming FDA review dates offer potential improvement over currently available treatments?
Szczotka: Semaglutide (Wegovy) [from Novo Nordisk] is currently approved as an adjunct to a reduced-calorie diet and increased physical activity for chronic weight management in adults and pediatric patients aged 12 years and older with obesity, as well as in adults with overweight in the presence of at least one weight-related comorbid condition, such as hypertension, type 2 diabetes, etc. It is also indicated to reduce the risk of major adverse cardiovascular events in adults with established cardiovascular disease and either obesity or overweight. Semaglutide is also being studied in metabolic dysfunction-associated steatohepatitis. Non-alcoholic steatohepatitis (NASH), also known as metabolic dysfunction-associated steatohepatitis (MASH), is the most severe form of non-alcoholic fatty liver disease (NAFLD), or metabolic dysfunction-associated fatty liver disease (MAFLD), and is characterized by an accumulation of fat in the liver. A once-weekly dose of semaglutide 2.4 mg helped to improve liver fibrosis with no worsening of steatohepatitis and to resolve steatohepatitis with no worsening of liver fibrosis in patients with MASH who had stage 2 or stage 3 liver fibrosis in the clinical trial. The data showed that 37% of patients treated with semaglutide achieved improvement in liver fibrosis without their steatohepatitis worsening at the trial’s 72-week mark, compared to 22.5% of patients on placebo. Further, 62.9% of patients on semaglutide saw their steatohepatitis resolved with no worsening of liver fibrosis versus 34.1% of patients on placebo. Rezdiffra [(resmetirom) from Madrigal Pharmaceuticals, Inc.] was the first MASH treatment to receive accelerated approval back in March 2024. Semaglutide appears to have comparable efficacy to Rezdiffra on both primary endpoints; however, Rezdiffra has an annual WAC [wholesale acquisition cost] of around $48,000, compared to Wegovy at $17,500. If approved for MASH, semaglutide may be considered as either first-line therapy due to the comparable efficacy and safety with lower cost or potentially in combination with Rezdiffra for patients who are not meeting stated endpoints.
AIS Health: Which of the cell and gene therapies look most promising and why?
Szczotka: Mozafancogene autotemcel [from Rocket Pharmaceuticals, Inc.], if approved, would be the first drug treatment option for Fanconi anemia. FA is a rare and serious inherited blood disorder that leads to bone marrow failure and is the most common cause of inherited bone marrow failure. It prevents bone marrow from making enough new blood cells for the body to work properly and can also cause bone marrow to make faulty blood cells, which can lead to certain types of cancers, including leukemia. Currently, treatment is through supportive therapy (i.e., blood transfusions), hematopoietic stem cell transplantation and androgen therapy for patients who are not good candidates for hematopoietic stem cell transplantation. About 80% of patients with FA will require a transplant within the first decade of their life. Gene therapy represents a potential new option for treatment. The results from a global clinical trial demonstrated that mozafancogene conferred sustained genetic correction in eight of 12 evaluable patients with more than 12 months of follow-up. The safety profile remains favorable with no known significant preliminary safety signals. Mozafancogene is a potentially curative or sustainable therapy response to prevent FA-related bone marrow failure and could potentially avoid stem cell transplant and related toxicities.
AIS Health: Which of the biosimilars expected in 2025 may have the biggest impact and why?
Szczotka: Biosimilar Stelara products will provide the largest impact in 2025. Stelara had over $10 billion in sales in 2024, and with seven ustekinumab biosimilars already FDA approved and due to be market available beginning in early 2025, this provides immediate market options. Some of the biosimilar ustekinumab biosimilar options have announced an 80% discount to the reference product pricing (approximately $14,000 per month) which should provide the opportunity for patient and payer cost savings in 2025.
AIS Health: If approved, CARsgen Therapeutics Holdings Limited’s zevorcabtagene autoleucel would be the third chimeric antigen receptor T cell (CAR-T) therapy to treat multiple myeloma. How does it compare/contrast with Carvykti (ciltacabtagene autoleucel) from Johnson & Johnson Innovative Medicine and Legend Biotech USA, Inc. and Abecma (idecabtagene vicleucel) from Bristol Myers Squibb and 2seventy bio, Inc.?
Szczotka: Zevorcabtagene autoleucel, if approved, would be the third available CAR-T therapy option for relapsed or refractory multiple myeloma. Zevorcabtagene autoleucel has not been directly compared with the other CAR-T therapies, but reviewing available information, each product’s specific antigen targets are slightly different, which may lead to potentially different efficacy and safety results, but the patient populations are relatively small in these studies. Currently Carvykti is approved as a second-line agent, and Abecma is an approved third-line agent in the therapy cascade. While not approved yet for use in the U.S., approvals in other countries have the use of zevorcabtagene as a fourth-line therapy. Additionally, clinical information presented seems to indicate the potential that Carvykti may provide an improved efficacy profile as compared to Abecma in terms of overall response rate and progression free survival.
AIS Health: What are takeaways from this report for health plans?
Szczotka: Some key areas from this specialty pipeline report include (1) the opportunity to capitalize on the potential savings from Stelara biosimilar products scheduled to be introduced in early 2025; (2) key products that may impact the health care and drug spend to consider include (i) the new ATTR-CM product Attruby and potential additional competition in later 2025 and 2026 with the TTR silencer products; (ii) Cobenfy as a new therapeutic option and new mechanism of action to treat schizophrenia; and (iii) two additional hemophilia product therapy options, Alhemo and Hympavzi. An additional takeaway is the continued need to closely monitor the upcoming pharmaceutical pipeline through pipeline publications, as this will help ensure proactive planning and management of emerging therapies.
By Angela Maas