Huge state-funded clinical trials have been instrumental in uncovering the benefits, or otherwise, of potential Covid treatments, and results are still rolling in. This week the UK’s Recovery trial concluded that Lilly’s Olumiant did indeed reduce the risk of death in very sick patients, albeit with a smaller benefit than some previous studies had found.
And, over in the US, the NIH scrapped an arm of the Activ-2 trial that was studying SAB Biotherapeutics’ antibody, SAB-185, because too few people were getting sick enough. The agency also told the UK’s Synairgen that its agent would not progress further in the study any time soon, presumably for the same reason.
Behind these moves lie Omicron and climbing background vaccination rates, which are leading to less severe symptoms and sending fewer people to hospital. As such, it is becoming increasingly hard to tease out an agent’s potential benefits, at least without running huge clinical studies.
Activ-2, a basket study that has put seven agents through their paces, is being carried out in patients with mild-to-moderate disease at high risk of ending up in hospital. Symptom duration and rate of hospitalisations are important endpoints.
The phase 3 arm studying SAB-185 had already been upsized. But this week the National Institute of Allergy and Infectious Diseases, the NIH division running the programme, accepted that the trial would still not be large enough to generate statistically rigorous findings.
Activ-2 is still ongoing, the NIAID confirmed to Evaluate Vantage, pointing out that the SAB-185 arm was the only one recruiting during the Omicron surge.
The agency this week told Synairgen to pause preparing clinical supplies for the start of the phase 3 portion of Activ-2 that will test SNG001. The inhaled beta interferon has already completed the phase 2 stage of its cohort, results from which are still awaited.
SNG001 recently failed to show a benefit in hospitalised patients in a large company-run trial. Should the NIAID road continue to close down, the tiny biotech, which is now worth only £50m ($66m), could struggle to justify further pandemic-focused investment.
| The Activ-2 arms: NIH-funded phase 2/3 outpatient trial |
|---|
| Project | Description | Company | Outcome |
| BMS-986414 and BMS-986413 | Subcutaneous MAb combination | Bristol Myers Squibb | Ph2 data awaited |
| SNG001 | Inhaled beta interferon | Synairgen | Ph2 data awaited; plans to start Ph3 on hold |
| SAB-185 | Intravenous polyclonal antibody | SAB Biotherapeutics | Arm closed in Mar 2022 after DSMB concludes trial likely to fail owing to lack of severe disease |
| Amubarvimab and romlusevimab | Infused MAb combination | Brii Biosciences | Positive results announced Aug 2021; no news since EUA submitted Oct 2021 |
| Evushield | Intramuscular MAb combination | Astrazeneca | Arm closed, Ph2 data expected in 1H 2022. Not approved in Activ-2 setting (EUA granted for pre-exposure prophylaxis in Dec 2021) |
| Bamlanivimab | Infused MAb | Lilly/Abcellera | EUA granted in combination with etesevimab in Sep 2021, but withdrawn Jan 2022 (no activity against Omicron) |
| Regen-Cov/ | Infused MAb | Regeneron | EUA granted Nov 2020, but withdrawn Jan 2022 (no activity against Omicron) |
| Ronapreve |
| Camostat mesilate | Oral protease inhibitor | Sagent Pharmaceuticals | Arm closed in Jun 2021 for futility |
| Source: NIH & company statements. |
Omicron might be damping demand for interventions at the milder end of Covid, but for the small number of people who end up very sick in hospital there remains a need for effective options. This is where the Recovery data on Olumiant come in, showing its mortality benefit, a finding made more impressive by the fact that patients were already on other drugs known to prevent death.
The study recruited over 8,000 patients, with 95% receiving steroids and 23% Actemra – agents that have become standard thanks to previous Recovery sub-studies. The primary finding was a statistically significant (p=0.026) 13% reduction in mortality for patients given Olumiant on top of standard of care, versus those on standard of care alone.
Researchers noted that this was smaller than the 43% reduction found by a meta-analysis of eight previous studies of a Jak inhibitor; when the Recovery result was incorporated the benefit came out at 20%.
Recovery was more than three times the size, in terms of statistical information, of the eight previous trials put together, the UK researchers noted in a preprint of the data.
Olumiant is already being widely used to treat Covid in hospitals throughout the world, of course; the drug has emergency use authorisation in the US, and was recently endorsed by the World Health Organization. Lilly reported that its sales almost doubled last year, with the rise driven by use in this setting.
The Recovery result confirms Olumiant as a valuable option, despite pointing to a benefit around half as great as previously thought. This in itself underlines the importance of running sufficiently powered studies to tease out the real benefit that various therapies might play.
https://www.evaluate.com/vantage/articles/news/trial-results/uk-recovery-trial-confirms-covid-benefit-olumiant
