Interleukin-4/13 Trap

Sanofi and Regeneron's Dupixent (dupilumab) secured FDA approval to treat bullous pemphigoid —  the first targeted therapy for the rare autoimmune skin disease. The decision announced Friday adds another feather to the IL-4/IL-13 inhibitor’s cap, marking its eighth clearance for an inflammatory condition in the US.“Today’s approval extends the remarkable ability of Dupixent to transform treatment paradigms for people living with a variety of diseases with underlying type 2 inflammation…including bullous pemphigoid,” said George Yancopoulos chief scientific officer at Regeneron.The latest label expansion was backed by results from the Phase II/III ADEPT trial, which evaluated Dupixent against placebo on top of standard-of-care oral corticosteroids in 106 adults with moderate-to-severe bullous pemphigoid over 52 weeks. Results showed the primary endpoint was met with 18.3% of Dupixent-treated patients achieving sustained disease remission at 36 weeks compared with 6.1% receiving placebo, representing a 12.2% difference. Additionally, 38.3% of Dupixent recipients met the secondary endpoint of clinically meaningful itch reduction on the Peak Pruritus Numerical Rating Scale versus 10.5% of their placebo counterparts, while the median cumulative oral corticosteroid dose was reduced to 2.8 g compared with 4.1 g.The additional indication is set to further boost Dupixent’s robust sales performance. The antibody raked $14.15 billion globally year, and annual revenue is anticipated to surpass $20 billion by 2030 — before the loss of patent exclusivity and entry of biosimilars.

GSK won a much-anticipated FDA approval for Nucala (mepolizumab) to treat chronic obstructive pulmonary disease (COPD) on Thursday. The green light — which comes more than two weeks past Nucala's PDUFA date — sets the anti–IL-5 antibody up to compete against Sanofi and Regeneron's Dupixent (dupilumab), the dominant player in the space.Specifically, Nucala was cleared as an add-on maintenance treatment for adults with inadequately controlled COPD and an eosinophilic phenotype. GSK decided to focus on patients with a peripheral blood eosinophil count of at least 300 cells/μl after the FDA rejected a broader COPD application in 2018.Dupixent is the first — and only other — biologic therapy approved for COPD, but key opinion leaders (KOLs) who spoke with FirstWord for a recent Therapy Trends report highlighted supporting data for several late-stage programmes, including Nucala, that suggest it could give the dual IL-4/IL-13 inhibitor a run for its money. For more, see Spotlight On: Biologics usher in a new era for COPD.While GSK had reported in September that Nucala significantly lowered the annualised rate of moderate or severe exacerbations in the Phase III MATINEE trial, meeting its primary endpoint, the pharma didn't reveal the specific data behind the study win until just a few weeks ago. A May publication in the NEJM detailed that Nucala reduced the exacerbation rate by 21% versus placebo from baseline through week 104, rising to 31% in patients with clinician-assessed chronic bronchitis. At the time, GSK's Chief Commercial Officer Luke Miels said the results were "very competitive" in comparison to Dupixent.Sanofi and Regeneron's drug was approved for COPD based on results from the BOREAS and NOTUS trials, which demonstrated a 30% and 34% reduction, respectively, in the annualised rate of moderate or severe exacerbations over 52 weeks, compared to placebo."Long-term follow-up studies have demonstrated that exacerbations are the single most important predictor of future risk, with particularly poor outcomes in those requiring hospital visits or admissions," Kaivan Khavandi, GSK's SVP and global head of respiratory, immunology & inflammation R&D, said in a company release. "Today there is hope for improved care for COPD patients with an eosinophilic phenotype."MATINEE also showed that Nucala led to a 35% reduction in the annualised rate of exacerbations leading to emergency department visits and/or hospitalisation versus placebo, a data point that Miels called "critical." However, the company noted that due to the study's statistical design, this secondary endpoint was only "nominally significant after adjustment for multiplicity." For related analysis, see Spotlight On: Can GSK deliver much needed pipeline momentum?Still, the hospitalisation-reduction data was enough to excite US-based pulmonologists surveyed in a recent FirstWord poll who said they were somewhat optimistic about Nucala's potential to carve out some market share away from Dupixent (See — Physician Views Results: GSK's Nucala may rival Dupixent in COPD with hospitalisation benefits).