Novartis’ asthma prospect fevipiprant has failed to improve lung function in two phase 3 trials. The negative top-line data deal a big blow to the prospects of a drug analysts tipped to achieve blockbuster sales if it cleared phase 3.
Fevipiprant is an antagonist of DP2, a receptor involved in the inflammatory processes that drive allergic asthma. The involvement of DP2 led researchers to identify the target as the basis for a new class of asthma drugs capable of treating the significant minority of patients with uncontrolled forms of the disease. However, DP2 drugs developed by AstraZeneca and Amgen have failed in the clinic.
Now, Novartis’ fevipiprant looks like it may join the list of failed DP2 drugs. Novartis snuck a brief look at the top-line findings of two phase 3 trials out in its financial results (PDF). Fevipiprant failed to improve lung function, as measured by FEV1, over placebo in either clinical trial.
The trials each enrolled around 700 patients with uncontrolled asthma and randomized them to take either fevipiprant or placebo once a day on top of standard of care treatment. The primary endpoint looked at change in FEV1 after 12 weeks. Novartis is yet to comment on the secondary endpoints, which tracked metrics including daytime asthma symptom score and quality of life.
Novartis’ brief statement intensifies the doubts raised by its phase 2b. Fevipiprant improved FEV1 at 12 weeks over placebo in the phase 2b, but details of the data, such as the lack of dose response, left scope to doubt whether it would succeed in phase 3. Analysts at Jefferies assigned a 30% probability of success, in part because of the failure of AstraZeneca and Amgen’s DP2 candidates.
The addition of fevipiprant to the list of DP2 failures could have negative implications for Gossamer Bio, which has a DP2 antagonist in phase 2b. When Gossamer raised $276 million in an IPO earlier in the year, it said Novartis’ fevipiprant phase 2 had clinically validated DP2 antagonism. That statement now looks premature, particularly when viewed in light of the failures of other DP2 drugs.
Gossamer expects to perform an interim analysis on its asthma phase 2b in the first half of 2020, with full top-line results to follow in the second half of the year. A failure there could sound the death knell for the DP2 antagonist class. The biotech's shares were down more than 30% premarket, as investors read this as a negative read-through.
Novartis is continuing with two other phase 3 trials that are looking at the effect of fevipiprant on moderate-to-severe asthma exacerbations. Top-line data are due in the first quarter.