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.