Specialty Drug Pipeline Quarterly Update: March 2023

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 articles for pipeline information on traditional drugs, biosimilars and gene/cell therapy.

New Drug Information

• Altuviiio^® [antihemophilic factor (recombinant), Fc-VWF-XTEN fusion protein-ehtl]: The U.S. Food and Drug Administration (FDA) has approved Sanofi’s Altuviiio, a first-in-class, high-sustained factor VIII replacement therapy. Altuviiio is indicated for routine prophylaxis and on-demand treatment to control bleeding episodes, as well as perioperative management (surgery) for adults and children with hemophilia A. Altuviiio is the first hemophilia A treatment that delivers normal to near-normal factor activity levels (over 40%) for most of the week with once-weekly dosing, and significantly reduces bleeds compared to prior factor VIII prophylaxis. The FDA’s approval was based on the Phase 3 clinical trial, XTEND-1 that demonstrated once-weekly Altuviiio prophylaxis met the primary endpoint of providing significant bleed protection for people with severe hemophilia A with a mean annualized bleeding rate (ABR) of 0.70 and a median ABR of 0.0.¹ Altuviiio is scheduled to be commercially available in April and will be priced at parity to the annual cost of treating a prophylaxis patient on Eloctate^® which is $12 per unit or a cost of $12,000 for a patient requiring 1000IU weekly or $625,000 annually.²
• Skyclarys™ (omaveloxolone): The FDA has approved Reata Pharmaceuticals’ Skyclarys for the treatment of Friedreich’s ataxia in adults and adolescents aged 16 years and older. Friedreich’s ataxia is a rare, genetic, neurodegenerative condition. Patients with Friedreich’s ataxia typically experience symptoms in childhood, including progressive loss of coordination, muscle weakness, and fatigue. Approximately 5,000 patients are currently diagnosed with Friedreich’s ataxia in the U.S. Skyclarys was approved based on a clinical trial that demonstrated patients treated with Skyclarys had a statistically significant lower modified Friedreich Ataxia Rating Scale (mFARS) score compared to placebo at Week 48, accounting for a placebo-corrected difference between the groups of –2.41 points.³ Skyclarys is available as a 50 mg capsule. Skyclarys has launched with an average wholesale price (AWP) of $37,000 per bottle (90 capsules).
• Daybue^® (trofinetide): The FDA approved Acadia Pharmaceuticals’ Daybue for the treatment of Rett syndrome in adult and pediatric patients two years of age and older. Daybue is the first FDA approved medication for Rett syndrome. Rett syndrome is caused by a genetic mutation in which the patients develop normally in infancy but then begin to deteriorate, losing their speech, motor control of their hands and other functions. There are approximately 4,500 diagnosed Rett syndrome patients in the US. Daybue is a twice daily oral solution that works by reducing inflammation in the brain, stopping certain types of cells from becoming overactive, and increasing the amount of the naturally occurring protein called IGF-1. Daybue was approved based on a Phase 3 Lavender trial which demonstrated that treatment with Daybue improved patients’ symptoms on two questionnaire scoring systems compared to placebo.⁴ Patients reported consistent benefits. Daybue is expected to be available by the end of April with an average list price estimated to be about $575,000 to $595,000 a year or $21.10 per milliliter for weight-based dosing.

New Indications

• Verzenio^® (abemaciclib): The FDA approved an expanded indication for Lilly’s Verzenio, in combination with endocrine therapy (ET), for the adjuvant treatment of adult patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-), node-positive, early breast cancer (EBC) at a high risk of recurrence. High risk patients eligible for Verzenio can now be identified solely based on nodal status, tumor size, and tumor grade (4+ positive nodes, or 1-3 positive nodes and at least one of the following: tumors that are 5 cm or Grade 3). This expanded adjuvant indication removes the Ki-67 score requirement for patient selection.
• Kevzara^® (sarilumab): The FDA expanded the indication of Sanofi and Regeneron’s Kevzara to include the treatment of adults with polymyalgia rheumatica (PMR) who had an inadequate response to corticosteroids or cannot tolerate corticosteroid taper.
• Jemperli^® (dostarlimab-gxly): The FDA granted a conversion from accelerated approval to full approval of GlaxoSmithKline (Tesaro) and AnaptysBio’s Jemperli with revised indication for treatment of patients with recurrent or advanced mismatch repair deficient (dMMR) endometrial cancer, as determined by an FDA-approved test, who have progressed on or after platinum-based regimens and are not candidates for curative surgery or radiation.

March News

• “A sudden change of heart at the FDA has sunk Sarepta Therapeutics’ stock. Two weeks after saying the FDA would assess its gene therapy without an advisory committee meeting, Sarepta has revealedthe agency will now convene experts to dig into the data on its Duchenne muscular dystrophy (DMD) submission. At the end of last month, Sarepta told investors it had completed the midcycle review for the SRP-9001 submission, and, with no significant safety or clinical issues coming up, the FDA had decided to proceed without an advisory committee meeting. The decision triggered a jump in Sarepta’s share price and put it on course to potentially win approval by May 29 without facing the scrutiny of independent experts.”⁵
• “BioMarin Pharmaceutical Inc. announced that it received notice from the FDA that the agency has extended review of the company’s Biologics License Application (BLA) for Roctavian™ (valoctocogene roxaparvovec) gene therapy for adults with severe hemophilia A. The FDA determined that the submission of the three-year data analysis from the ongoing Phase 3 GENEr8-1 study constituted a Major Amendment due to the substantial amount of additional data and set a new PDUFA Target Action Date of June 30, 2023. The company had previously communicated that this data submission could be qualified as a Major Amendment.”⁶
• “Ahead of its advisory committee hearing to discuss Biogen’s ALS drug tofersen, the FDA appeared open to approving the drug, newly released briefing documents show. Citing the need for flexibility in a devastating disease like ALS, regulators signaled a willingness to consider greenlighting tofersen based on its effect on a certain protein associated with ALS despite a failed pivotal trial. The documents come after regulatory flexibility was part of the same rationale the agency expressed when approving an ALS drug last September from Amylyx Pharmaceuticals, indicating the FDA’s openness to approving new treatments for the disease. “Despite the notable limitations of a failed study and the many post hoc exploratory analyses that were conducted after [the Phase III trial], the Division considers that the data may suggest a treatment effect of tofersen in SOD1-ALS,” the FDA wrote. “This is a very rare and devastating disease; therefore, it is of utmost importance that we give full consideration to all of the available data.” Tofersen did not achieve the primary goal of its Phase 3 VALOR trial, failing to prove it could slow SOD1-ALS patients’ functional decline better than a placebo. Reported in October 2021, the results showed there were higher odds that any observable drug effect on function was due to random chance than tofersen producing its desired outcome. Biogen said the p-value for the primary endpoint was p=0.97.”⁷
• “The FDA is moving to optimize the development of gene therapies, including encouraging the use of biomarkers to help get accelerated approval of therapies for serious conditions, an agency official said. Biomarkers, such as pulse and blood pressure, are characteristics of the body that you can measure. The FDA will support using biomarkers as substitutes for other biological indicators in gene-therapy clinical trials to help clinch “accelerated approval”, said the agency’s Peter Marks.”⁸

References

1. https://www.sanofi.com/en/media-room/press-releases/2023/2023-02-23-21-00-00-2614759
2. https://www.sanofi.com/en/media-room/press-releases/2023/2023-02-23-21-00-00-2614759
3. https://www.neurologylive.com/view/fda-approves-omaveloxolone-first-treatment-friedreich-ataxia
4. https://www.rettsyndrome.org/trofinetideapproved/
5. https://www.fiercebiotech.com/biotech/fda-shocks-sarepta-ordering-adcomm-dmd-gene-therapy-sudden-change-heart
6. https://investors.biomarin.com/2023-03-06-BioMarin-Provides-Update-on-FDA-Review-of-ROCTAVIAN-TM-Valoctocogene-Roxaparvovec-Gene-Therapy-for-Adults-with-Severe-Hemophilia-A
7. https://endpts.com/fda-indicates-willingness-to-approve-biogen-als-drug-despite-failed-phiii-study/
8. https://www.reuters.com/world/us/us-fda-official-says-agency-needs-start-using-accelerated-approval-gene-2023-03-20/