GSK-3862995B

AstraZeneca’s investigational antibody for chronic obstructive pulmonary disease has succeeded in two late-stage studies, despite having previously failed in a mid-stage trial. And, unexpectedly, the company revealed Friday the drug yielded positive data in a relatively broad population, potentially increasing its market reach. The drugmaker said that tozorakimab, which targets interleukin-33, hit the primary endpoints in the twin OBERON and TITANIA trials, in both cases cutting the rate of moderate-to-severe COPD exacerbations — acute attacks of breathlessness, coughing and increased sputum production — compared with placebo. The company called these reductions statistically significant and highly clinically meaningful, though it did not give figures. The two trials are part of a four-study program called LUNA. According to the Friday data, tozorakimab succeeded in both trials’ primary populations of former smokers, as well as in their overall populations. The latter groups included a broader spectrum of patients, including former and current smokers with different levels of lung function and numbers of eosinophils in their blood. High levels of eosinophils, a type of white blood cell, are thought to spur inflammation in respiratory diseases. Subjects in the trials took a 300 mg dose of the antibody, injected once a month for a year on top of standard of care. Tozorakimab was well tolerated, AstraZeneca said, with a “favorable” safety profile. Analysts from Jefferies wrote in a same-day note that tozorakimab’s success in the overall populations could mean that their current projection for worldwide peak sales of the drug is now “potentially conservative, pending detailed data.” The forecast stands at $3 billion at present, and assumes success only in former smokers. They wrote that the broad efficacy could mean that the upper end of AstraZeneca’s target sales range for the drug of $3 billion to $5 billion may be achievable. AstraZeneca said that the data from the two studies will be showcased in greater detail at a medical meeting. One question is why these studies hit when an earlier Phase 2a trial called FRONTIER-4 flopped . That trial used a different endpoint — the amount of air exhaled during a forced breath, assessed at three months. But it also used a higher dose of 600 mg, given monthly. Other IL-33 blockers also have a history of disappointing in COPD. Sanofi and Regeneron’s itepekimab posted underwhelming, though technically successful, Phase 3 data last May. A month later, Roche’s astegolimab stumbled in a late-stage trial, though it hit in a Phase 2b. GSK is also pursuing this mechanism. An asset, codenamed GSK3862995B, is in a Phase 1 trial, with data possibly due next year. AstraZeneca believes tozorakimab could be the first drug in its class to gain approval. It works by blocking the signaling of certain forms of IL-33, which reduces both inflammation and the mucus dysfunction that can worsen COPD, the company said. Still, approval is not a done deal. The drug is in two more Phase 3 trials, named MIRANDA and PROSPERO. The former is testing the 300 mg dose of tozorakimab, but given every two weeks rather than every four. PROSPERO is a long-term extension trial consisting of patients who completed the OBERON or TITANIA trials, with a readout at 104 weeks. Data from both of these studies should come by mid-year. Tozorakimab is also in late-stage research as a therapy for severe viral lower respiratory tract disease, and is in a mid-stage trial in asthma.