SAGE-324

Biogen acquired felzartamab through the $1.15bn Human Immunology Biosciences (HI-Bio) acquisition in July 2024. Image credit: Tada Images / Shutterstock. The US Food and Drug Administration (FDA) has granted a breakthrough therapy designation for its monoclonal antibody felzartamab as a treatment for late antibody-mediated rejection without T cell-mediated rejection in kidney transplant patients. The company has previously received breakthrough therapy designation for felzartamab in primary membranous nephropathy (PMN) indication and orphan drug designations for the therapy in PMN and antibody-mediated rejection. Biogen also plans to start Phase III trials evaluating felzartamab in three indications, antibody-mediated rejection, PMN and IgA nephropathy (IgAN), next year. The news also resulted in a modest uptick of Biogen’s stock, which was up by 1.9% at the market close yesterday (9 October) compared to the market close on the previous day. The company’s stock has suffered a decline in recent months. July was a turbulent month for Biogen as the European Medicines Agency (EMA) refused to approve its Alzheimer’s therapy Leqembi (lecanemab), developed in collaboration with Eisai . Soon after, its essential tremor therapy, SAGE-324, developed in partnership with Sage Therapeutics failed in a Phase II trial and the companies abandoned development. The FDA’s decision for the breakthrough therapy designation was based on positive data from a Phase II trial (NCT05021484). The study enrolled 22 patients who experienced late antibody-mediated rejection at least six months post-kidney transplantation. After 24 weeks, 82% of patients in the treatment arm saw a resolution of antibody-mediated rejection, compared to 20% in the placebo group. Of the nine patients who experienced resolution with felzartamab at 24 weeks, 67% maintained resolution at 52 weeks. Biogen has also seen positive mid-stage results with felzartamab in both PMN and IgAN indications. See Also: Merck unveils €290m biosafety testing facility in Maryland, US Boehringer and Circle Pharma link to develop new cancer treatment Felzartamab is an anti-CD38 targeting monoclonal antibody. It is a recent addition to Biogen’s portfolio and was added as part of the $1.15bn Human Immunology Biosciences (HI-Bio) acquisition in July 2024. Felzartamab was originally developed by MorphoSys as a possible competitor to Johnson & Johnson (J&J) and Genmab ’s multiple myeloma therapy Darzalex (daratumumab). Celgene briefly acquired the rights to the therapy in 2013 before HI-Bio licensed it for development outside China in 2022. GlobalData, the parent company of Pharmaceutical Technology , expects the monoclonal antibody to pull in over $776m by 2032, should the therapy get approved.

Sage Therapeutics is reeling from another mid-stage setback as its investigational medicine dalzanemdor has missed the mark in a Phase 2 mild cognitive impairment trial. The drug, an NMDA receptor positive allosteric modulator, was not significantly better than placebo at helping Alzheimer’s patients with mild cognitive impairment or mild dementia improve on a scale known as the Wechsler Adult Intelligence Scale Fourth Edition Coding Test. Dalzanemdor had failed on the same primary endpoint in another Phase 2 in patients with Parkinson’s disease this spring. At the time, Sage executives tried downplaying any read-through from the Parkinson’s trial to the Alzheimer’s study. The 12-week trial, dubbed LIGHTWAVE, randomized 174 Alzheimer’s patients. With the primary endpoint miss, Sage said it is discontinuing further development of dalzanemdor, or SAGE-718, in Alzheimer’s. Sage’s share price $SAGE was down more than 12% before Tuesday’s opening bell. Next up is Huntington’s disease. The Cambridge, MA-based biotech said it anticipates reporting topline results from another Phase 2 of the investigational drug in patients with cognitive impairment associated with Huntington’s by the end of this year. The drugmaker said that is its lead indication for the medicine. “While we are disappointed by the results of the LIGHTWAVE Study, we are grateful to participants, investigators, care partners, patient advocates and the Alzheimer’s community who helped make this important research possible,” CEO Barry Greene said in a press release. “We hope our work and these findings help to inform future research.” It marks another blow to Sage’s pipeline. In July, the company and partner Biogen said their oral medicine SAGE-324 failed a Phase 2 in essential tremor . Biogen walked away from that piece of their pact two months later. Sage continues to evaluate whether SAGE-324 can be applied for other brain conditions. The duo secured an FDA green light for their drug Zurzuvae in postpartum depression last August, but it was rejected in the broader population of major depressive disorder. Sage is also evaluating a slate of other investigational medicines, including SAGE-689, SAGE-421 and SAGE-319.