Horizon Therapeutics has chalked up another win for its CD40 drug candidate dazodalibep, linking the molecule to improved outcomes in a second Sjögren’s syndrome study before it sells up to Amgen in a $28 billion deal.
Decades of work on CD40 have so far failed to fulfill the therapeutic potential hinted at by evidence of the costimulatory protein’s role in immune activation, but Horizon’s candidate has enjoyed midphase trial success. Having hit the primary endpoint in one trial in Sjögren’s, a systemic autoimmune disease, last year, Horizon has begun 2023 with a top-line win in a neighboring population to claim a unique double phase 2 victory in the indication.
The first trial enrolled people with moderate to severe systemic disease activity, and the second targeted patients with moderate to severe localized symptoms. Horizon claims it is the first company to run phase 2 trials that hit their primary endpoints in both Sjögren’s patient populations.
In the second study, investigators randomized 109 patients with localized symptoms to receive monthly intravenous doses of dazodalibep or placebo. By Day 169, patients on dazodalibep had experienced a 1.8-point reduction in their scores on the ESSPRI symptom scale compared to a 0.53-point reduction in the placebo group. The difference between the two reductions was big enough for the clinical trial to hit its primary endpoint.
The study also met some secondary quality-of-life endpoints. Horizon highlighted fatigue as one area in which it linked dazodalibep to statistically significant improvements. Horizon is yet to share detailed safety data but said the therapy was well tolerated, with COVID-19, nasopharyngitis and anemia the most common adverse events.
With two midphase wins under its belt, Horizon now plans to work with the FDA to design a phase 3 trial and push on into the next stage of development this year. Sjögren’s is one of several opportunities open to dazodalibep, which is also in development in focal segmental glomerulosclerosis, rheumatoid arthritis and kidney transplant rejection.
Horizon added dazodalibep to its pipeline in 2021 by acquiring Viela Bio for $3 billion. Viela took the drug with it when it spun out of AstraZeneca and went on to study the candidate as a treatment for multiple autoimmune diseases. With Amgen expected to close its takeover of Horizon in the first half of the year, ownership of dazodalibep is set to change hands once again in the coming months.