Gossamer Bio's DP2 inhibitor GB001 fails 2 midphase trials

Gossamer Bio CEO Sheila Gujrathi, M.D. (Gossamer Bio)

Gossamer Bio’s GB001 has failed in two midphase trials in asthma and chronic rhinosinusitis. The failures come months after Novartis dumped rival DP2 inhibitor fevipiprant in response to a clutch of phase 3 flops.

The promise of DP2 inhibition has attracted companies including Amgen, AstraZeneca and Novartis. Yet, none of those heavyweight drug developers were able to build on evidence that activation of the prostaglandin receptor drives allergy and inflammation and go on to create efficacious therapies. Gossamer Bio funded its attack on the target by raising $276 million in an IPO last year.

Now, Gossamer Bio’s GB001 has joined the list of DP2 drugs to fail in clinical trials. Gossamer Bio has fresh data from two midphase clinical trials of the oral antagonist of the DP2 pathway. Neither trial was a success. 

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The larger of the two clinical trials randomized 480 patients with uncontrolled, moderate-to-severe eosinophilic asthma to receive one of three doses of GB001 or placebo on top of standard of care. After 24 weeks of daily dosing, patients in the GB001 arms performed no better on a measurement of asthma worsening than their peers in the placebo cohort. 

Participants were classed as worsening if their peak expiratory flow, FEV1, rescue medication use or scores on an asthma control questionnaire deteriorated by a certain amount, or if they suffered the occurrence of severe asthma exacerbations.

GB001 was statistically no better than placebo at stopping those outcomes. A secondary measure that looked at the annualized severe exacerbation rate—an expected phase 3 endpoint—also found no statistical benefit to taking GB001 over placebo.   

However, Gossamer Bio pointed to numeric reductions in the odds of asthma worsening versus placebo of 32% to 35% across the three GB001 arms as evidence that the drug may work. Gossamer Bio also tracked a statistically significant improvement in time to asthma worsening in the low and high dose GB001 cohorts and performed a post hoc analysis that linked the drug to lower odds of suffering three or more forms of asthma worsening. 

The signs of efficacy have persuaded Gossamer Bio to look past the primary endpoint failure and forge ahead with further development of GB001. 

“We believe these data provide important information for designing a well-powered phase 3 program for GB001 in severe asthma. We plan to engage in global regulatory discussions in order to inform our thinking around potential partnerships or strategic alternatives for this program,” Gossamer Bio CEO Sheila Gujrathi, M.D., said in a statement.  

Gossamer Bio is plotting a move into phase 3 in asthma despite a second phase 2a trial in patients with chronic rhinosinusitis also failing. That trial missed its primary and secondary endpoints, leading Gossamer Bio to scrap plans to develop GB001 in chronic rhinosinusitis.

The two midphase failures add to the case against DP2 inhibitors. Last year, Novartis reported data from four phase 3 trials of its DP2 drug fevipiprant in different groups of asthma patients. None of the trials succeeded, leading Novartis to halt development of the asset. Fevipiprant joined DP2 drugs once in development at Amgen, AstraZeneca and Boehringer Ingelheim on the scrapheap.

Shares in Gossamer Bio fell almost 30% in response to the data. The stock was already trading at around half the price it commanded before the second set of Novartis’ failed phase 3 clinical trials dampened expectations for GB001.

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