Atea’s woes grow while other Covid readouts approach
Big upcoming events include data from a trial of Pfizer’s oral antiviral Paxlovid in patients at risk of severe illness.
Things had already been looking bad for Atea’s oral Covid-19 antiviral AT-527. Now they have got worse, with the group’s partner Roche abandoning the project. Atea will press on alone, and though it looks to have missed the Covid-19 boat there are plenty of big readouts for other groups coming up, an analysis by Evaluate Vantage shows.
One of these will involve Pfizer’s Paxlovid, which has already impressed in the Epic-HR trial in non-hospitalised patients at risk of developing severe Covid-19. The next set of results, from the Epic-SR study, will come in low-risk non-hospitalised people, a tougher population to crack.
Interestingly, Epic-SR includes a cohort of vaccinated patients with breakthrough Covid infections, while Epic-HR only enrolled unvaccinated subjects. Pfizer said yesterday that it had filed for emergency use authorisation for Paxlovid, but it is unclear whether a nod could include vaccinated people; the decision is in the hands of the FDA.
However, a positive outcome in Epic-SR is far from assured given that others have struggled in this setting. Notably, AT-527 flunked the phase 2 Moonsong trial, which allowed vaccinated people and those without underlying health conditions (Atea and Roche get a Covid-19 antiviral warning, October 19, 2021).
This failure prompted the partners to amend the ongoing phase 3 Morningsky study to focus on high-risk, unvaccinated patients, among other things. Consequently results, which had been expected by the end of this year, will now not come until the second half of 2022.
Roche has clearly decided that AT-527 will no longer be able to compete, even if Morningsky does succeed. And, given that the big pharma group will no longer be involved, even the revised timeline could be at risk. The readout is still on track, Atea’s management told Leerink, but the analysts noted that Roche must now transfer technology and materials to Atea, possibly causing delays.
The analysts also floated the idea that Atea might be able to find a new partner, but this seems unlikely. Atea’s stock was off 20% this morning.
Paxlovid vs molnupiravir
While the omens in low-risk Covid might not be good, there are reasons to be optimistic about Paxlovid’s chances. The project combines a protease inhibitor with the HIV drug ritonavir, so works differently from AT-527 and Merck & Co/Ridgeback’s molnupiravir, which both target viral RNA polymerase.
Paxlovid also showed stellar efficacy in Epic-HR. At 89% this was a much higher figure than the 50% that molnupiravir demonstrated in its similar trial, Move-Out.
Caution should be used with cross-trial comparisons, but these will inevitably be made again when post-exposure prophylaxis studies of both agents read out in the first half of next year.
Meanwhile, many small players also have big Covid catalysts coming up. Synairgen’s SNG001, an inhaled formulation of interferon beta, got a boost last month with news that it was moving into the phase 3 arm of the NIH-funded Activ-2 study, in outpatients.
The group’s own pivotal trial, Sprinter, will yield data early next year – but this is in hospitalised patients, another setting that has proven tricky.
Redhill Biopharma, meanwhile, recently saw opaganib fail in hospitalised patients but has another bite of the cherry with a second oral project, RHB-107; that asset's phase 2/3 study is in outpatients, so it might have a better chance than its forerunner.
One asset that does not feature here is Glaxosmithkline’s anti-GM-CSF MAb otilimab; the company said during its third-quarter results that it was discontinuing development in Covid. However, Glaxo is still in play in Covid vaccines, where it has two shots on goal, via Sanofi and Medicago, due to yield data by the end of the year.
|Selected ongoing trials of Covid-19 therapies|
|Unnamed vaccine||Monovalent and bivalent recombinant protein vaccines||Prevention||Ph3, 21,046 pts, data due Q4 2021|
|MT-2766||Recombinant coronavirus-like particle vaccine||Prevention||Ph2/3, 30,918 pts, data due Q4 2021|
|Pfizer||Paxlovid (PF-07321332/ritonavir)||Oral antiviral||Outpatients (low-risk)||Epic-SR, ph3, 3,000 pts, data due Q1 2022|
|Synairgen||SNG001||Inhaled interferon beta 1a regulator||Hospitalised||Sprinter, ph3, 610 pts, data early 2022|
|Kiniksa Pharmaceuticals||Mavrilimumab||Anti-GM-CSF receptor alpha MAb||Hospitalised||Ph2/3, 588 pts, data due Q1 2022|
|Redhill Biopharma||RHB-107 (upamostat)||Oral serine protease inhibitor||Outpatients||Ph2/3, 310 pts, part A data due Q1 2022 (safety only)|
|Pfizer||Paxlovid (PF-07321332/ritonavir)||Oral antiviral||Prevention||Epic-Pep, ph3, 2,634 pts, data due Q1/Q2 2022|
|Merck & Co/ Ridgeback||Molnupiravir||Oral RNA polymerase inhibitor||Prevention||Move-Ahead, ph3, 1,332 pts, data due "spring 2022"|
|Veru||Sabizabulin (Veru-111)||Oral tubulin polymerisation inhibitor||Hospitalised||Ph3, 300 pts, ends Jan 2022|
|Foresee Pharmaceuticals||FP-025||Oral MMP 12 inhibitor||Hospitalised||Ph2/3, 403 pts, ends Feb 2022|
|INO-4800/ VGX-3100||Vaccine, administered intradermally followed by electroporation with Cellectra 2000 device||Prevention||Innovate, 7,517 pts, interim data due H1 2022|
|Adagio Therapeutics||ADG20||Neutralising MAb||Prevention||Evade, ph2/3, 6,412 pts, data due Q2 2022|
|Adagio Therapeutics||ADG20||Neutralising MAb||Outpatients||Stamp, ph2/3, 1,084 pts, interim efficacy analysis due Q2 2022|
|Atea||AT-527||Oral antiviral||Outpatients||Morningsky, ph3, 1,386 pts, data due H2 2022|
|Ensovibep||Darpin (antibody mimetic)||Outpatients||Empathy, ph2/3, 2,100 pts, ends May 2022|
|Note: excludes basket trials. Source: Evaluate Pharma & clinicaltrials.gov.|
To see more of Vantage's recent Covid-19 coverage, click here.