AstraZeneca ($AZN) has halted a Phase IIa trial of the severe asthma drug it licensed from Synairgen (LON:SNG). The Big Pharma took action after an interim analysis raised doubts about whether the study could deliver meaningful data against its primary endpoint, throwing the future of the program into question and wiping 40% off Synairgen’s share price.
The clinical trial was designed to give an inhaled formulation of interferon beta-1a or a placebo to 220 asthmatics. By giving the nebulized solution of interferon beta-1a to participants as they started with symptoms of colds or the flu, AstraZeneca hoped to show the drug, AZD9412, prevented severe asthma exacerbations. AstraZeneca limited participation in the trial to people who had recently suffered severe asthma exacerbations that were suspected to have been caused by a cold or flu.
However, an interim analysis found a “very low number of reported severe exacerbations,” according to AstraZeneca. As the primary endpoint looks at the proportion of subjects to suffer severe asthma exacerbations during their 14 days of treatment, AstraZeneca concluded the low rate of such events “could make primary endpoint conclusions difficult.” The Big Pharma has responded by stopping the study.
AstraZeneca will look through the secondary endpoint data to see if there is a path forward for the program, although the low number of exacerbations has affected these measures, too. Six of the secondary endpoints relate to aspects of exacerbations. Faced with a hole in a key section of its data, AstraZeneca is looking to endpoints that predict the worsening of the condition to exacerbation for evidence of the efficacy of AZD9412.
Failure to find reasons for optimism would close off another source of future sales for AstraZeneca. Synairgen would bear the brunt of such a setback, though. The microcap is in line to earn up to $225 million (€204 million) in milestones on top of the $7.5 million it pocketed when it struck the licensing deal with AstraZeneca. If Phase IIa is the end of the line for AZD9412, Synairgen will earn a fraction of the potential deal value. Shares in the company fell 40% following the news.
AZD9412 has made missteps in the clinic before. A Phase II trial Synairgen ran before AstraZeneca came on board missed its primary endpoint of change in asthma symptoms. Synairgen sought solace in data associating AZD9412 with a fall in severe exacerbations, leading to that outcome being made the primary endpoint of the next study.
Synairgen developed the drug in response to evidence interferon beta deficiencies explain the effect the common cold has on the lung function of asthmatics. By providing asthmatics with the interferon beta they naturally lack, AstraZeneca and Synairgen thought they could enhance antiviral responses and prevent exacerbations.