Ianalumab

An investigational drug for the autoimmune condition Sjögren's disease has scored a phase 3 win for Amgen, marking a positive sign for the Horizon Therapeutics-acquired pipeline that has so far struggled to gain traction. The phase 3 OASIZ 301 study enrolled 651 patients with moderate-to-severe Sjögren's, a disease where the patient’s immune system attacks the tear and salivary glands. Dry eyes and mouth are common symptoms, but the disease can also be more severe. There are no medicines specifically approved by the FDA to treat Sjögren’s, with symptoms often managed by anti-inflammatory medications. Amgen today reported that after 48 weeks of treatment, patients given dazodalibep, a fusion protein targeting the CD40 ligand, had significantly improved scores on the EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) compared to placebo, hitting the trial’s primary endpoint. The most common side effects were mild or moderate nasal inflammation, urinary tract infection, hypertension and infusion-related reactions, Amgen announced. Detailed results from the trial will be shared at an upcoming medical conference. “The rapid and sustained improvement observed in systemic disease activity reinforces our confidence in dazodalibep and the broader phase 3 program as we work to deliver a new, highly differentiated option for people living with this debilitating autoimmune disease,” Jay Bradner, M.D., Amgen’s executive vice president of R&D, artificial intelligence and data, said in Amgen’s release. OASIZ 301 enrolled patients with both moderate-to-severe Sjögren's symptoms and systemic disease. Another phase 3 trial, OASIZ 303 , is focused on patients with similar symptoms but mild systemic disease activity. Amgen is also running a long-term extension study that is open to patients from both OASIZ trials. "This first positive phase 3 readout with dazodalibep adds validation for the CD40L mechanism of action in [Sjögren's], and could have positive read-through to the ongoing OASIZ 303 study," said analysts from William Blair in a note to investors. "Although we note that the two studies did enroll distinct patient populations." The FDA will likely require two positive phase 3 readouts before considering approval, the analysts added. "Patients with Sjögren's disease contend with debilitating symptoms and systemic manifestations for which no approved disease-modifying therapy exists," Ghaith Noaiseh, M.D., a rheumatologist at the University of Kansas Medical Center and lead investigator of OASIZ 301, said in the release. "These topline results provide further support for dazodalibep as an emerging treatment for improving systemic disease activity and represent an important advance for the field." The biopharma industry has struggled with Sjögren's recently. Novartis and Sanofi have dropped such programs in recent years, though Novartis is still developing an antibody called ianalumab for Sjögren's. That antibody notched a pair of phase 3 wins last year, even with strong placebo effects. Meanwhile, Astellas culled a STING inhibitor for the disease in April after first terminating a phase 1 trial, while Amgen itself followed up by dropping another Horizon-acquired drug meant to treat the disease in May. That drug, adezkibart, is an antibody targeting FMS-like tyrosine kinase 3 ligand that was scrapped after its phase 2 trial failed an interim futility analysis. Amgen has few experimental drugs remaining from its $27.8 billion buyout of Horizon in 2023, which centered on the approved products Uplizna, Krystexxa and Tepezza. Dazodalibep was not developed by Horizon, but was rather picked up by the former biotech through the $3 billion acquisition of AstraZeneca spinout Viela Bio in 2021. Editor's note: This story was updated at 11:05 a.m. E.T. with analyst commentary.

Dive Brief:An experimental Amgen drug has succeeded in the first of two Phase 3 trials in Sjgren's syndrome, driving the California biotechnology giants stock price up as much as 5% on Tuesday.Amgen didnt provide specific details about the performance of its drug dazodalibep. But it said in a Tuesday statement that treatment led to a statistically significant and clinically meaningful improvement on a widely used measure of disease activity after 48 weeks, meeting the trials primary objective. Positive effects were observed as early as four weeks after treatment and persisted through the evaluation period, Amgen said.Investigators didnt spot an imbalance in the rate of blood clots or opportunistic infections in the Phase 3 study, a potential concern of drugs with dazodalibeps mechanism. Side effects were generally mild to moderate, and study discontinuations were infrequent and balanced across study arms, the company said.Dive Insight:Sjgrens has been a tricky target for drugmakers. There are no approved treatments that can alter the course of the condition, in which the immune system errantly attacks moisture-producing glands and causes chronic dry eyes and mouth, pain, inflammation and other health problems. Patients have a higher risk of lymphoma as well.Dazodalibep interferes with a key communication channel between immune cells. Blocking this CD40-CD40L pathway is meant to blunt the hyperactive immune response and formation of tissue-damaging autoantibodies in Sjgrens. The approach showed promise in earlier testing, with participants in a Phase 2 trial experiencing a reduction in symptoms and disease activity.The drug came to Amgen after changing hands multiple times. It was originally discovered by AstraZeneca, which spun it into a startup, Viela Bio, that Horizon Therapeuticsacquired in 2021. Amgen then bought Horizon two years later, inheriting dazodalibep along with multiple other prospects.Dazodalibep is now among the more closely watched prospects in Amgens pipeline. The results announced Tuesday come from the first of two pivotal studies in Sjgrens. The second, in patients who have a high symptom burden, is expected to produce data in the fourth quarter.“These topline results provide further support for dazodalibep as an emerging treatment for improving systemic disease activity and represent an important advance for the field, Ghaith Noaiseh, the studys lead investigator and an immunology professor at the University of Kansas Medical Center, said in a statement provided by Amgen.Without detailed findings theyll be disclosed at a future medical meeting its not yet clear how Amgens drug stacks up against other emerging competitors. Novartis has an experimental therapy called ianalumab that could be cleared by regulators this quarter. Bristol Myers Squibb is also due to report Phase 3 data testing its drug Sotyktu, a marketed treatment for psoriasis, in Sjgrens.The study specifics Amgen eventually presents will help inform positioning against ianalumab, wrote David Risinger, an analyst at Leerink Partners, in a note to clients. Risinger added that his team and other analysts have very low expectations for Bristol Myers study.In a separate note,William Blair analyst Matt Phipps wrote that he was encouraged by the announcement given his team has viewed the dazodalibep program as relatively high risk. He cautioned, though, that Amgens two Phase 3 trials involve distinct patient populations and the company will need victories in both studies to win regulatory approval. '