Biogen and UCB’s gamble on advancing into phase 3 on the back of a failed study looks to have paid off, with the partners reporting positive top-line results in systemic lupus erythematosus (SLE) and outlining plans to start a second pivotal trial.
The phase 3 trial assessed dapirolizumab pegol, an anti-CD40L drug candidate that Biogen and UCB have been jointly developing since 2003. A phase 2b trial of the molecule missed its primary endpoint in 2018, but the partners saw separation versus placebo on multiple clinical and immunological parameters. After seeing the mixed data, Biogen and UCB opted to start one, rather than the customary two, phase 3 trials.
Biogen and UCB now have enough confidence in dapirolizumab pegol to commit to starting a second trial this year. The bet on a second study is underpinned by data from the first phase 3 trial, which linked the drug candidate to improvements in moderate to severe disease activity on a composite lupus scale.
The improvements caused the trial to hit its primary endpoint. Neither party has disclosed the numbers behind the primary endpoint success, but comments made by Iris Löw-Friedrich, M.D., Ph.D., chief medical officer at UCB, on an earnings call in July provide a pointer. Löw-Friedrich said UCB considered a 20% improvement over placebo the minimum for clinically meaningful efficacy.
Biogen and UCB will share details of how the actual data compare to that target at an upcoming medical congress. The partners could also share data on clinical improvements they reported for key secondary endpoints measuring disease activity and flares. Löw-Friedrich said in July that, while primary endpoint data will be the key drivers, the consistency of secondary endpoints will also be important.
Buoyed by the 48-week data, Biogen and UCB plan to move patients in the existing trial into a long-term open-label study and start a second phase 3. Talking at a Stifel event in March, Priya Singhal, head of development at Biogen, said she expected to need two studies for the registrational package. Choosing to run the trials in sequences, rather than in parallel, dialed down the risk of moving into phase 3.
The downside is sequential development takes longer. If Biogen and UCB had run two phase 3 trials from the get-go, they could now be preparing to seek approval. The first phase 3 trial began in August 2020. If the second study takes as long, the partners could report data around the end of 2028.
Success in the second study would boost Biogen’s efforts to diversify its portfolio and add growth drivers. Dapirolizumab is part of a broader push into lupus at the Big Biotech, which is also testing the internally developed anti-BDCA2 antibody litifilimab in phase 3 trials. Biogen was bolder with litifilimab, taking the candidate into a suite of simultaneous late-phase studies.