Specialty Drug Pipeline Update: May 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 article for pipeline information on traditional drugs.

New Drug Information

• Qalsody^® (tofersen): The U.S. Food and Drug Administration (FDA) has granted accelerated approval of Biogen and Ionis’ Qalsody to treat patients with amyotrophic lateral sclerosis (ALS) associated with a mutation in the SOD1 gene. Qalsody, is meant for the 1% to 2% of ALS patients who have a mutation called SOD1, or 330 people in the U.S., with 120 patients newly diagnosed each year, according to Biogen. Qalsody is administered into the spinal canal and is an RNA-based therapy designed to reduce toxic SOD1 protein and preserve cell function. Biogen was granted approval of Qalsody based on the use of neurofilament as a surrogate biomarker, which is reasonably likely to predict clinical benefit, in data from the three-part VALOR trial. Qalsody missed its primary endpoint in the Phase 3 VALOR trial. The trial demonstrated a non-statistically significant 1.2-point difference on the ALSFRS-R scale.¹ In March, an FDA advisory committee voted unanimously that its impact on neurofilament could predict clinical benefit. Qalsody has launched with a wholesale acquisition cost (WAC) of $14,230 per 28 days.
• Vowst™ (fecal microbiota spores, live-brpk): The FDA has approved Seres Therapeutics’ Vowst designed to modulate the disrupted microbiome to a state that resists C difficile colonization and growth for prevention of recurrent C difficile infection. Citing CDC data, Seres estimates there will be about 156,000 recurrent  difficilecases in the U.S. in 2023. Vowst is an oral medication administered as four capsules daily for three days. In the Phase 3 trial, ECOSPOR III, Vowst beat placebo in reducing the risk of recurrent C. difficile infections. Eight weeks after dosing, 12% of patients in the Vowst group and 40% in the placebo arm experienced recurrence.² Seres Therapeutics has launched Vowst with a WAC $17,500 per treatment, primarily dispensed in the outpatient setting through the pharmacy benefit.
• Elfabrio^® (pegunigalsidase alfa-iwxj): The FDA has approved Protalix BioTherapeutics’ Elfabrio for treatment of adult patients with Fabry disease. Fabry disease is a rare genetic progressive disorder caused by deficient activity of the lysosomal α-galactosidase-A enzyme, which leads to progressive buildup of globotriaosylceramide (Gb3) in blood vessel walls throughout the body. Elfabrio is a hydrolytic lysosomal neutral glycosphingolipid-specific enzyme. Elfabrio’s approval was based on the Phase 3 trial that demonstrated that Elfabrio was noninferior to agalsidase beta in controlling the annualized rate of change in estimated glomerular filtration rate (eGFR slope) -2.4 and -2.3mL/min/1.73 m²/year on pegunigalsidase alfa and agalsidase beta respectively.³ Elfabrio is supplied as a preservative-free solution in a single-dose vial. Each vial contains 20mg/10mL of pegunigalsidase alfa-iwxj. Treatment is administered by intravenous infusion every two weeks. Launch and price are pending.\
• Vyjuvek™ (beremagene geperpavec-svdt): The FDA approved Krystal Biotech’s Vyjuvek for the treatment of patients six months of age or older with dystrophic epidermolysis bullosa (DEB). There are two types of DEB: recessive and dominant. The dominant form of the disease is usually milder, while the recessive type is more debilitating and can lead to disfigurement, vision loss and potentially fatal complications, according to the FDA. Vyjuvek is designed to address the genetic root cause of DEB by delivering functional copies of the human COL7A1gene to provide wound healing and sustained functional COL7 protein expression with redosing. Vyjuvek is a non-invasive, topical, re-dosable gene therapy that is administered by a health care professional in either a health care professional setting or in the home. Vujuvek’s approval was supported by data from the GEM-1/2 and GEM-3 clinical trials which demonstrated in a 31-patient clinical trial, 65% of Vyjuvek-treated wounds closed completely, compared with 26% of placebo-treated wounds.⁴ Launch and price are pending.
• Epkinly™ (epcoritamab-bysp): The FDA granted accelerated approval of AbbVie’s Epkinly as the first T-cell engaging bispecific antibody for the treatment of adult patients with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL), not otherwise specified (NOS), including DLBCL arising from indolent lymphoma, and high-grade B–cell lymphoma (HGBL), after two or more lines of systemic therapies. DLBCL is the most common type of NHL, comprising of an estimated 30,400 U.S. cases in 2022 and 150,000 new cases each year globally. Epkinly demonstrated a 61 percent overall response rate (ORR), 38 percent complete response, and 15.6-month median duration of response in challenging-to-treat R/R DLBCL patients.⁵ Launch and price are pending.
• Yuflyma^®(adalimumab-aaty): The FDA has approved Celltrion’s Yuflyma a high-concentration (100mg/mL) and citrate-free formulation of Humira^® (adalimumab) biosimilar. The FDA granted approval for the treatment of eight conditions: rheumatoid arthritis, juvenile idiopathic arthritis, psoriatic arthritis, ankylosing spondylitis, Crohn’s disease, ulcerative colitis, plaque psoriasis, and hidradenitis suppurativa.⁶ Yuflyma is scheduled to launch in July with pricing to follow. Celltrion is seeking interchangeability designation from the FDA in fourth quarter of 2024.

New Indications

• Padcev^® (enfortumab vedotin-ejfv): The FDA approved a new indication of Astellas and Seagen’s Padcev for use in combination with pembrolizumab (Merck’s Keytruda) for first-line treatment of patients with unresectable locally advanced or metastatic urothelial cancer who are ineligible for cisplatin chemotherapy.
• HyQvia^® (Immune Globulin Infusion; Recombinant Human Hyaluronidase): Takeda’s HyQvia has been granted an expanded indication to include primary immunodeficiency.
• Polivy^® (polatuzumab vedotin-piiq): The FDA approved an additional indication of Genentech (Roche)’s Polivy for use in combination with rituximab plus cyclophosphamide, doxorubicin and prednisone (R-CHP) for the treatment of people with previously untreated diffuse large B-cell lymphoma (DLBCL).
• Trikafta^® (elexacaftor/tezacaftor/ivacaftor and ivacaftor): The FDA expanded Vertex’s Trikafta indication to include cystic fibrosis, two through five years of age with at least one F508del mutation or a mutation that is responsive based on in vitro data.
• Kalydeco^® (ivacaftor): The FDA approved an additional indication for Vertex’s Kalydeco to include cystic fibrosis patients with CFTR gene mutations.

May News

• “At long last, Eli Lilly has found success in its decades-long effort to develop a treatment for Alzheimer’s disease. The company announced that its experimental drug, donanemab, slowed a key measure of cognitive and functional decline by 35% over 18 months in a subset of patients with early Alzheimer’s disease. The highly anticipated Phase III study, known as TRAILBLAZER-ALZ 2, also succeeded on all its primary and secondary endpoints, bucking a long series of failed Alzheimer’s studies from Lilly and others. The company said it plans to submit the drug to the FDA “as quickly as possible” this quarter.”⁷
• “An FDA advisory committee voted 8-6 that the benefits of Sarepta Therapeutics’ gene therapy for Duchenne muscular dystrophy outweigh its risks, lending their backing to accelerated approval of the treatment. In a day-long meeting, outside experts heard arguments over whether the FDA should allow use of Sarepta’s gene therapy, known as SRP-9001, based on a surrogate endpoint for patients with Duchenne muscular dystrophy who are able to walk and have a confirmed mutation.”⁸
• “The FDA has once again raised safety concerns around the use of Intercept’s Ocaliva in NASH, concluding in briefing documents ahead of an upcoming advisory committee meeting that it “cannot justify OCA use in NASH subjects with Stage 2 or 3 fibrosis.” Intercept’s push for an accelerated approval was first rejected by the FDA in 2020 after multiple delays. At the time, regulators said they were uncertain if the drug’s benefit based on a surrogate endpoint, reduction in liver fibrosis, was enough to outweigh potential risks, according to Intercept. Executives, however, said they were blindsided. “At no point during the review did the FDA communicate that OCA was not approvable on an accelerated basis, and we strongly believe that the totality of data submitted to date both meet the requirements of the Agency’s own guidance and clearly support the positive benefit-risk profile of OCA,” former CEO Mark Pruzanski said in 2020.”⁹

References

1. https://investors.biogen.com/news-releases/news-release-details/fda-grants-accelerated-approval-qalsodytm-tofersen-sod1-als
2. https://ir.serestherapeutics.com/news-releases/news-release-details/seres-therapeutics-and-nestle-health-science-announce-fda
3. https://www.prnewswire.com/news-releases/chiesi-global-rare-diseases-and-protalix-biotherapeutics-announce-fda-approval-of-elfabrio-pegunigalsidase-alfa-iwxj-for-the-treatment-of-fabry-disease-301820680.html
4. https://ir.krystalbio.com/news-releases/news-release-details/krystal-biotech-receives-fda-approval-first-ever-redosable-gene
5. https://www.fda.gov/drugs/drug-approvals-and-databases/fda-grants-accelerated-approval-epcoritamab-bysp-relapsed-or-refractory-diffuse-large-b-cell
6. https://www.empr.com/home/news/yuflyma-a-citrate-free-high-concentration-biosimilar-to-humira-gets-fda-approval/
7. https://endpts.com/lillys-alzheimers-drug-donanemab-succeeds-in-phase-iii-trial/
8. https://endpts.com/fda-adcomm-backs-accelerated-approval-of-sareptas-duchenne-gene-therapy-in-close-vote/
9. https://endpts.com/intercepts-nash-hopeful-gets-preliminary-thumbs-down-in-fda-briefing-docs/