Specialty Pipeline Quarterly Update: SEPTEMBER 2022

This quarterly 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 cell/gene therapy. 

New Drug Information

• Xenpozyme® (olipudase alfa-rpcp): The U.S. Food and Drug Administration (FDA) has approved Sanofi’s Xenpozyme for the treatment of non-central nervous system (non-CNS) manifestations of acid sphingomyelinase deficiency (ASMD, also known as Niemann-Pick disease type A and type B) in adult and pediatric patients. ASMD is a rare, progressive, and potentially life-threatening disease that results from a deficient activity of the enzyme acid sphingomyelinase (ASM), which is found in special compartments within cells called lysosomes and is required to breakdown lipids called sphingomyelin. If ASM is absent or not functioning as it should, sphingomyelin cannot be metabolized properly and accumulates within cells, eventually causing cell death and the malfunction of major organ systems. The deficiency of the lysosomal enzyme ASM is due to disease-causing variants in the sphingomyelin phosphodiesterase 1 gene (SMPD1). The estimated prevalence of ASMD is approximately 2,000 patients in the United States, Europe, and Japan.1 Xenpozyme was approved based on the Phase 3 ASCEND trial that demonstrated significantly improved lung function and significantly reduced spleen volume for Xenpozyme-treated patients at 52 weeks. Additionally, Xenpozyme’s data remained consistent throughout the 6.5-year outcomes for five adult patients with ASMD and two-year outcomes in 20 pediatric patients, as well as the open-label extension from the Phase 3 ASCEND trial in adults. Results showed the percent predicted lung function (DLco) mean increase was 55.3%, spleen volume mean decrease was 59.5%, and liver volume mean decrease was 43.7% compared to baseline of original study.1 Xenpozyme launch and price are pending.
• Stimufend® (pegfilgrastim-fpgk): Fresenius Kabi’s Stimufend was approved by the FDA as a pegfilgrastim biosimilar. Stimufend is indicated for use in patients with non-myeloid malignancies receiving myelosuppressive anti-cancer drugs associated with a clinically significant incidence of febrile neutropenia. Stimufend is the fifth approved pegfilgrastim biosimilar using Amgen’s Neulasta as a reference product. The company expects to launch the product in a prefilled syringe early next year and in an on-body injector following FDA approval with pricing to follow.²

• Sotyktu® (deucravacitinib): The FDA approved BMS’ Sotyktu for the treatment of adults with moderate-to-severe plaque psoriasis who are candidates for systemic therapy or phototherapy. Sotyktu is a first-in-class, oral, selective, allosteric tyrosine kinase 2 (TYK2) inhibitor. Sotyktu’s approval was based on the Phase 3 POETYK PSO-1 and POETYK PSO-2 trials that evaluated the percentage of patients who achieved Psoriasis Area and Severity Index (PASI) 75 and the percentage of patients who achieved static Physician’s Global Assessment (sPGA) score of 0 to 1 with at least a two-grade improvement from baseline, compared with placebo, at week 16.
  • Findings from the POETYK PSO-1 and POETYK PSO-2 trials, respectively, included the following:
    • Patients achieving PASI 75 response at week 16: 58% and 53% for deucravacitinib vs 13% and 9% for placebo (both P <.0001) and 35% (P<.0001) and 40% (P =.0004) for apremilast.³
    • Patients achieving PASI 90 response at week 16: 36% and 27% for deucravacitinib vs 4% and 3% for placebo (both P <.0001) and 20% (P=.0002) and 18% (P =.0046) for apremilast.³ 
    • Patients achieving sPGA 0/1 at week 16: 54% and 50% for deucravacitinib vs 7% and 9% for placebo (both P <.0001) and 32% and 34% for apremilast (both P <.0001).³

Sotyktu has launched with an average wholesale price of $7,397 per bottle of 30 tablets.

• Rolvedon™ (eflapegrastim-xnst): The FDA approved Spectrum Pharmaceuticals’ Rolvedon injection to decrease the incidence of infection, as manifested by febrile neutropenia, in adult patients with non-myeloid malignancies receiving myelosuppressive anti-cancer drugs associated with clinically significant incidence of febrile neutropenia. Rolvedon’s approval was based on two identical Phase 3 clinical trials, ADVANCE and RECOVER, which evaluated the safety and efficacy of Rolvedon in early-stage breast cancer patients for the management of neutropenia due to myelosuppressive chemotherapy. In both studies, Rolvedon demonstrated non-inferiority (NI) in mean duration of severe neutropenia (DSN) and a similar safety profile to pegfilgrastim.4 Rolvedon also demonstrated non-inferiority to pegfilgrastim in the mean DSN across all four cycles in both trials. Rolvedon is scheduled to launch fourth quarter 2022 with pricing to follow.
• Terlivaz™ (terlipressin): The FDA approved Terlivaz for injection. Terlivaz is the first FDA-approved product indicated to improve kidney function in adults with hepatorenal syndrome (HRS) with rapid reduction in kidney function, an acute and life-threatening condition requiring hospitalization. Terlivaz was approved based on the Phase 3, CONFIRM trial which used a surrogate endpoint of renal function improvement, avoidance of dialysis and short-term survival to demonstrate that Terlivaz reversed HRS-1 in 29% of patients who were treated with Terlivaz compared to 16% treated with placebo.5 In July 2020, the FDA Advisory Committee voted 8 to 7 to recommend approval of Terlivaz. The panel suggested that the benefits of Terlivaz outweigh the safety risks, Terlivaz and placebo groups experienced serious side effects at roughly the same rate: 65% versus 61%. Terlivaz launch and price are pending.

New Indications

• Pemazyre® (pemigatinib): The FDA expanded Incyte’s Pemazyre indication to include treatment of relapsed or refractory myeloid/lymphoid neoplasms (MLNs) with FGFR1 rearrangement.

September News

• “Bluebird bio has reported its financial results and business highlights for the second quarter of 2022, in which the company revealed the anticipated launch of both betibeglogene autotemcel (beti-cel) and elivaldogene autotemcel (eli-cel) gene therapies in the fourth quarter of the year. The news comes after both therapies were endorsed by the FDA Cell Tissue & Gene Therapy Advisory Committee (CTGTAC) in June 2022. Beti-cel is under priority review for the treatment of people with transfusion-dependent beta-thalassaemia (beta-thal), a rare genetic blood disease caused by a gene defect that impairs the ability of red blood cells to produce hemoglobin. Patients with the most severe form of beta-thal develop life-threatening anemia and have to undergo regular blood transfusions, a lengthy process typically needed every two to five weeks. Eli-cel is under priority review for the treatment of early active cerebral adrenoleukodystrophy (CALD) in patients under the age of 18 who do not have an available and willing matched sibling donor. CALD is a rare neurodegenerative disease that primarily affects young children and leads to irreversible loss of neurologic function and death. Beti-cel and eli-cel have Prescription Drug User Act Fee (PDUFA) goal dates of 19 August 2022 and 16 September 2022, respectively. If approved, the company anticipates that both therapies will be available in the fourth quarter of 2022.”⁶
• “Amylyx Pharmaceuticals Inc. shares climbed after its controversial treatment for amyotrophic lateral sclerosis won the support of a panel of U.S. regulatory advisers, putting the product on track for likely clearance. During a rare second panel meeting on Wednesday, the FDA peripheral and central nervous system drugs advisory committee voted 7-2 to back approval of the treatment. During a meeting in March, FDA advisers found that data from Amylyx’s relatively small initial trial was insufficient to prove that AMX0035 slowed ALS progression. The negative decision put the FDA in a bind, as the agency, under pressure from disease activists, has promised to exercise flexibility in approving drugs for dire illnesses such as ALS, given the urgent need for better treatments. New data from Amylyx “is not unequivocally persuasive, but nonetheless is quite reassuring,” said Liana Apostolova of Indiana University School of Medicine, who voted in favor of the drug this time after opposing it in March. She said she took into account that ALS “is a horrific disorder, it is a death sentence.””⁷
• “Apellis Pharmaceuticals, Inc., a global biopharmaceutical company and leader in complement, today announced top-line data at 24 months showing increased effects over time with intravitreal pegcetacoplan, an investigational, targeted C3 therapy, in the Phase 3 DERBY and OAKS studies in geographic atrophy (GA) secondary to age-related macular degeneration (AMD). In a pre-specified analysis of GA lesion growth over 24 months, both monthly and every-other-month (EOM) pegcetacoplan showed a clinically meaningful reduction in GA lesion growth from baseline compared to sham (all p-values are nominal): DERBY: 19% monthly, p=0.0004; 16% EOM, p=0.0030. OAKS: 22% monthly, p<0.0001; 18% EOM, p=0.0002. Between months 18-24, the pegcetacoplan treatment effect accelerated compared to previous six-month periods, with robust reductions of GA lesion growth versus sham (all p-values are nominal). The increased effects were driven by a greater slowing of lesion growth by pegcetacoplan and not by an increase in the lesion growth rate in the sham group, which was highly consistent over each of the four six-month intervals (1.0+/-0.05 mm²).”⁸