Synairgen's pivotal COVID-19 SPRINTER trial falls at final hurdle, sending stock into downward spiral

Synairgen’s time riding the COVID-19 wave has come crashing to a close. Its inhaled interferon beta candidate SNG001 posted a clean sweep of failures against key endpoints in a phase 3 clinical trial of hospitalized COVID-19 patients, prompting investors to flee despite Synairgen’s search for a silver lining.

U.K.-based Synairgen was one of the big stock market winners of the scramble for COVID-19 treatments early in the pandemic, with investors driving its share price up from around 6 pence sterling ($0.08) at the start of 2020 to almost 250 pence at its peak on the strength of early data in hospitalized patients. The stock fell from the high it hit in August 2020 but was still trading in the 170 pence to 200 pence range in the month before the phase 3 data drop.

The data caused a dramatic reappraisal of Synairgen’s prospects. With the study missing its primary and key secondary endpoints, investors sent the stock crashing down to around 25 pence, up on its pre-pandemic level but down more than 80% on the price it commanded just before the data drop.

That precipitous decline reflects Synairgen’s outright failure against the primary endpoints. The time to hospital discharge through Day 28 was the same in the SNG001 and placebo arms regardless of whether an intention-to-treat or per-protocol analysis was performed, and patients on the investigational drug were no more likely to recover to “no limitation of activities” than their peers in the control group were.

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Synairgen fingered changes to standard of care for hospitalized COVID-19 patients as a possible cause of the failure of its SPRINTER trial. In the phase 3 study, 87% of patients received systemic corticosteroids for COVID-19 at baseline, reflecting the validation of drugs such as dexamethasone and hydrocortisone in the setting. No  participants in Synairgen’s phase 2 clinical trial received corticosteroids.

The emergence of corticosteroids as standard of care happened before SPRINTER began, though, meaning Synairgen knew the bar it needed to clear to show efficacy had changed at the outset. U.K. researchers published initial clinical data showing dexamethasone reduces mortality in June 2020. The World Health Organization strongly recommended systemic corticosteroid use in September 2020. Synairgen began its phase 3 trial in January 2021.

Pitted against the current standard of care, SNG001 missed the primary and three key secondary endpoints. The secondary endpoints looked at progression to severe disease or death, progression to intubation or death and progression to death, all over a 35-day time frame. While SNG001 failed to beat placebo against any of the measures, Synairgen hailed the rate of progression to severe disease or death in the placebo group, 14.7%, versus the SNG001 cohort, 10.7%, as “an encouraging trend.”

In a statement, Synairgen CEO Richard Marsden said the trend “merits further investigation in a platform trial.” Synairgen also has an ongoing shot at resurrecting SNG001, with the National Institutes of Health continuing to study the candidate in home-based patients. But, with COVID-19 joining asthma on its list of failures, investors have sharply downgraded their expectations.