Specialty Pipeline Update: March 2022

New drugs, new indications and news of note

This monthly pipeline wrap up provides a review of newly approved specialty drugs, recent specialty drug launches, new indications and news of note on specialty drugs in the approval process. See separate article for pipeline information on traditional drugs.

New Drug Information

Pyrukynd^®(mitapivat): U.S. Food and Drug Administration (FDA) has approved Pyrukynd (mitapivat) for the treatment of hemolytic anemia in adults with pyruvate kinase (PK) deficiency, a rare, debilitating, lifelong hemolytic anemia. Pyrukynd is a first-in-class, oral PK activator and the first approved disease-modifying therapy for this disease. The Phase 3 ACTIVATE trial of Pyrukynd achieved its primary endpoint by demonstrating a statistically significant increase in hemoglobin in patients with PK deficiency who are not regularly transfused with 40% of patients randomized achieving a hemoglobin response, compared to 0 patients randomized to placebo. The Phase 3 ACTIVATE-T trial of Pyrukynd also achieved its primary endpoint of demonstrating a statistically significant and clinically meaningful reduction in transfusion burden for patients who are regularly transfused (33% of patients achieved a transfusion reduction response, compared with individual historical transfusion burden standardized to 24 weeks). Twenty two percent of patients were transfusion-free during the fixed-dose period.¹ Pyrukynd has launched with an average wholesale price (AWP) of $552 per tablet.

Releuko^® (filgrastim-ayow): The FDA approved Amneal’s Releuko as a biosimilar version of Amgen’s Neupogen^® (filgrastim). Releuko is indicated to:

• Decrease the incidence of infection‚ as manifested by febrile neutropenia‚ in patients with nonmyeloid malignancies receiving myelosuppressive anti-cancer drugs associated with a significant incidence of severe neutropenia with fever
• Reduce the time to neutrophil recovery and the duration of fever, following induction or consolidation chemotherapy treatment of patients with acute myeloid leukemia (AML)
• Reduce the duration of neutropenia and neutropenia-related clinical sequelae‚ febrile neutropenia, in patients with nonmyeloid malignancies undergoing myeloablative chemotherapy followed by bone marrow transplantation (BMT)
• Reduce the incidence and duration of sequelae of severe neutropenia‚ in symptomatic patients with congenital neutropenia‚ cyclic neutropenia‚ or idiopathic neutropenia

Releuko was approved on two clinical trials that confirmed pharmacokinetic and bioavailability between Releuko and Neupogen. Releuko has not been granted interchangeable status by the FDA. The FDA noted that biosimilars marketed in the U.S. typically have launched with initial list prices 15% to 35% lower than comparative list prices of the reference products. According to IQVIA^®, U.S. annual sales for filgrastim for the 12 months ended December 2021 were $407 million, of which $275 million represents biosimilar sales.² Releuko is the third biosimilar to Neupogen to be approved by the FDA after Sandoz’s Zarxio^® (filgrastim-sndz) and Pfizer’s Nivestym^® (filgrastim-aafi). Releuko has launched with AWP $273.60 – $437.76 per vial/syringe.

Vonjo^® (pacritinib): The FDA granted accelerated approval of CTI BioPharma’s Vonjo for the treatment of adults with intermediate or high-risk primary or secondary (post-polycythemia vera or post-essential thrombocythemia) myelofibrosis with a platelet count below 50 × 10⁹/L. Vonjo is an oral kinase inhibitor with specificity for JAK2 and IRAK1, without inhibiting JAK1. Vonjo was approved based on the Phase 3 PERSIST-2 trial which demonstrated that 29% of patients with baseline platelet counts below 50 × 10⁹/L who were treated with pacritinib 200mg had a reduction in spleen volume of at least 35% compared to 3% of patients receiving best available therapy, which included ruxolitinib.³The recommended dosage of Vonjo is 200mg orally twice daily. Vonjo has launched with a wholesale acquisition cost (WAC) of $19,500 per month.

Carvykti^® (ciltacabtagene autoleucel; cilta-cel): The FDA approved Legend Biotech Corporation’s Carvykti for the treatment of adults with relapsed or refractory multiple myeloma (RRMM) who have received four or more prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody. Carvykti is a chimeric antigen receptor T-cell (CAR-T) therapy with two B-cell maturation antigen (BCMA)-targeting single domain antibodies and is given as a one-time infusion with a recommended dose range of 0.5 to 1.0 x 10⁶CAR-positive viable T cells per kg of body weight. In the pivotal CARTITUDE-1 study, deep and durable responses were seen in patients with RRMM, with a high overall response rate (ORR) of 98 percent including 78 percent of the patients achieving stringent complete response (sCR).⁴ At a median of 18 months follow-up, the median duration of response (DOR) was 21.8 months. Carvykti has launched with a wholesale acquisition cost (WAC) of $465,000.

New Indications

None

March News

“The FDA is staying cautious after data came out suggesting that one of BioMarin’s experimental gene therapies might have the potential to drive cancers. Although details remain sparse, BioMarin said that its gene therapy for the rare disease phenylketonuria, or PKU, will remain on hold after the FDA asked for additional non-clinical — i.e., lab-based or animal studies — to assess “the theoretical oncogenic risk to human study participants.” Those studies, the company said, are “expected to take several quarters.””⁵

“The adoption of biosimilars tends to accelerate quickly after market introduction, according to Cardinal Health. And their use has grown significantly since 2015. Momentum is “stronger than ever” in the biosimilar space, Cardinal Health’s specialty solutions president Heidi Hunter said. Last year, Viatris’ Semglee became the first interchangeable biosimilar, meaning it can be substituted for the original insulins without a doctor’s input. The drug references Sanfoi’s long-acting insulin, Lantus. Upon launching in November, Viatris said the list price would be set at about $400 for a package of five 3 mL pens, which is about $20 cheaper than the list price for the branded version. The company also simultaneously launched an unbranded version of its insulin glargine product at a 65% list price discount, which the company called “the lowest WAC for any insulin glargine pen on the market to date.” While it’s unclear what 2022 will hold in store for biosimilar pricing and coverage, Cardinal says one message is clear: Momentum in this space is accelerating. Analysts say biosimilars are on track to reduce U.S. drug expenditure by $133 billion by 2025. “2022 is set to be a turning point in the U.S., as biosimilars expand into new therapeutic areas and sites of care, and reimbursement models continue to evolve,” Hunter said.”⁶

“With two of its prized gene therapies on clinical hold and another, Zynteglo, pulled from the market in Europe seven months ago after it was approved for use, these are not the best of times for bluebird bio. So after updating the status of lovo-cel, eli-cel and beti-cel (Zynteglo) in its fourth quarter and 2021 earnings report, bluebird illuminatedits dire financial situation, saying that its cash needs “raise substantial doubt regarding its ability to continue as a going concern.”⁷

“Sales of Bristol Myers Squibb’s Revlimid crescendoed at $12.8 billion in 2021, the final year of exclusivity for the multiple myeloma treatment. But now, BMS can no longer hold off generic competition. Last month, Sandoz and Stada Arzneimittel revealed that launches of their generic versions of Revlimid are underway in Europe. Now Teva has become the first to do the same in the U.S. Teva will provide Lenalidomide capsules in 5mg, 10mg, 15mg and 25mg strengths, it said, for the treatment of multiple myeloma in combination with dexamethasone, certain myelodysplastic syndromes and mantle cell lymphoma following specific prior treatment. The company did not note what it would charge.”⁸

References

1. https://investor.agios.com/news-releases/news-release-details/agios-announces-fda-approval-pyrukyndr-mitapivat-first-disease
2. https://www.businesswire.com/news/home/20220302005951/en/Kashiv-Biosciences-Receives-Approval-for-Its-First-Biosimilar-RELEUKOTM-filgrastim-ayow
3. https://www.prnewswire.com/news-releases/cti-biopharma-announces-fda-accelerated-approval-of-vonjo-pacritinib-for-the-treatment-of-adult-patients-with-myelofibrosis-and-thrombocytopenia-301492159.html
4. https://www.businesswire.com/news/home/20220228006246/en/CARVYKTI%E2%84%A2-ciltacabtagene-autoleucel-BCMA-Directed-CAR-T-Therapy-Receives-U.S.-FDA-Approval-for-the-Treatment-of-Adult-Patients-With-Relapsed-or-Refractory-Multiple-Myeloma
5. https://endpts.com/biomarin-gene-therapy-could-be-on-hold-for-several-quarters-after-fda-mandates-new-preclinical-tests/
6. https://endpts.com/last-year-was-one-of-the-most-eventful-in-us-biosimilars-history-but-these-analysts-say-2022-should-be-a-turning-point/
7. https://www.fiercepharma.com/pharma/bluebird-bios-cash-needs-raise-doubts-about-its-ability-continue-going-concern
8. https://www.fiercepharma.com/pharma/bristol-myers-squibbs-revlimid-finally-faces-competition-us-tevas-generic-launch?utm_source=email&utm_medium=email&utm_campaign=LS-NL-FiercePharma&oly_enc_id=6999D8336467C2P