Amlitelimab

Summing up Sanofi’s patchy clinical track record so far this year, the company’s head of R&D Houman Ashrafian, Ph.D., acknowledged that “drug development is a tough thing.”\n Some of Sanofi’s most high-profile readouts this year can’t have made for easy reading at the French pharma’s Paris headquarters.In April, the company revealed that its anti-OX40L-ligand antibody amlitelimab had flunked a phase 2 asthma trial. The same month, the drugmaker reported that its oral TNF inhibitor balinatunfib missed the goal of a midstage psoriasis study. Weeks later, the Regeneron-partnered IL-33 candidate itepekimab failed one of a pair of phase 3 studies in chronic obstructive pulmonary disease.Even a phase 3 win for amlitelimab—which Sanofi secured as part of its $1.1 billion acquisition of Kymab back in 2021—in atopic dermatitis (AD) earlier this month received a lukewarm reception from analysts and dented the company’s stock price.Despite these setbacks, Sanofi’s head of R&D, Houman Ashrafian, Ph.D., told Fierce Biotech that he takes a “pretty pragmatic” approach to the Big Pharma’s portfolio.“We’ve had a year which has been mixed, but that reflects the risks of drug development, particularly in immunology and inflammation, and particularly in areas where … the clinical trial space has been shaped by preexisting molecules,” Ashrafian said in an interview.The R&D chief spoke to Fierce ahead of the release of phase 2 data from Sanofi for brivekimig that the company hopes will tell a more positive story. The pharma has been assessing the anti-TNFa/OX40L nanobody in a trial of 71 patients with moderate-to-severe hidradenitis suppurativa, a rare inflammatory skin condition.While the study wasn\'t powered for statistical significance, 67% of brivekimig-treated patients saw a 50% or greater decrease in total abscess and inflammatory nodule count at week 16, a result Sanofi called “clinically meaningful.“ A total of 54% of brivekimig patients saw abscesses reduced by 75% compared to 22% of the placebo cohort.Unveiling the results ahead of a presentation at the European Academy of Dermatology and Venereology 2025 Congress in Paris, Alyssa Johnsen, M.D., Ph.D., Global Therapeutic Area Head, Immunology and Oncology Development at Sanofi, said the data “exemplify our deep understanding of pathway biology and commitment to exploring novel platforms and technologies.““We are encouraged by these results and look forward to continuing to explore brivekimig, and the impact of dual TNF and OX40 ligand inhibition, on the inflammation driving the burdensome symptoms of HS,” Johnsen added in a Sept. 17 release.In his interview with Fierce days earlier, Ashrafian also alluded to the “positive study” for brivekimig, suggesting that the “OX40 ligand portfolio is looking pretty good.” The other OX40L success—at least in Sanofi\'s eyes—is the anti-OX40L antibody amlitelimab, which hit the primary endpoint of a phase 3 AD trial earlier this month by showing that 35.9% and 46%, respectively, of two patient cohorts had seen a 75% or greater improvement in their eczema.While the study was a win on paper, the results fell at the bottom end of analysts’ predictions, prompting a 9% share price decline for the French pharma in one day.When asked by Fierce whether he was surprised by the market reaction, Ashrafian pointed to the fact that the study “comfortably” hit its key endpoints, and amlitelimab appeared to be “safest in class.”“My perspective was that this was a credible result,” he said.“This is a meaningful contributor to the AD landscape, which is hugely biologically under-penetrated,” added Ashrafian, who noted that “the incumbents in AD look like they will all become blockbusters.” Not feeling the pressure One explanation that analysts gave for the high stakes placed on that amlitelimab readout was growing concerns that the failures of itepekimab and balinatunfib in the clinic this year cast doubt over how Sanofi will replace the losses accrued when Dupixent finally falls off the patent cliff around 2031.Despite being Sanofi’s head of R&D, Ashrafian denied that he feels under increased scrutiny to ensure he has a winner on his hands.“I\'m not really feeling the pressure,” he said. “I\'m excited to be doing what we\'re doing—we’ve got a great pipeline.”“It always surprises me when people say they have questions about R&D credibility,” Ashrafian said. “We\'re not going to get everything right. We\'re not perfect, but actually we\'ve got one of the best late-stage portfolios of any company in the industry today.”The late-stage portfolio includes an eagerly awaited phase 3 readout of the BTK inhibitor tolebrutinib in multiple sclerosis in the coming weeks. Despite having suffered its own clinical difficulties—namely falling short in two out of a trio of studies last year—Sanofi is still hoping to score an FDA approval in the specific indication of non-relapsing secondary progressive MS.Ashrafian also said the pharma’s leadership has “gone from good to great” in recent months with the appointment of Christopher Corsico, M.D., as Sanofi’s global head of development in May, followed by Marcia Kayath, M.D., Ph.D., taking on the chief medical officer role earlier this month. The execs previously worked at GSK and BioMarin, respectively.Summing up Sanofi’s patchy clinical track record so far this year, Ashrafian acknowledged that “drug development is a tough thing.”“I\'m humble and reflective in the face of failures, but it\'s part of our business,” he said. “If you can\'t deal with some of those slings and arrows of outrageous fortune, I think this particular job is not the one to take on.”

Sanofi unveiled detailed results from a mid-stage study of brivekimig — its dual-target nanobody inhibiting TNF-alpha and OX40L — in hidradenitis suppurativa (HS) at the European Academy of Dermatology and Venereology (EADV) congress on Wednesday.The Phase IIa HS-OBTAIN study top-lined earlier this year, showing clinically meaningful improvements with brivekimig versus placebo in biologic-naïve patients with HS. This led to the company prioritising the therapy in HS over amlitelimab — an OX40 blocker that had failed to show comparable efficacy.The HS-OBTAIN trial randomised 86 adults with moderate-to-severe HS to receive brivekimig 150 mg or placebo every two weeks for 16 weeks, followed by a 12-week open-label phase and 8-week safety follow-up. The primary endpoint was HiSCR50 — defined as ≥50% reduction in total abscess and inflammatory nodule count with no increase in abscess or draining fistula count — at week 16 in biologic-naïve patients.Results showed 67% of patients receiving brivekimig achieved HiSCR50 response versus 37% in the placebo arm. The study also met key secondary endpoints, with 54% of brivekimig-treated patients achieving HiSCR75 versus 22% with placebo, and 31% reaching HiSCR90 compared with 9% of placebo recipients. Additionally, mean draining tunnel count decreased by 56% with brivekimig versus an increase of 10.9% with placebo.In terms of safety, Sanofi said that brivekimig was well tolerated with no serious adverse events (AEs) reported. The most frequent AEs occurring in more than 10% of participants were nasopharyngitis and headache.Brivekimig, also known as SAR442970, is being explored across multiple immune-mediated diseases and inflammatory disorders.