Vaccines against Covid-19 are generating very impressive data, but there remains a pressing need for effective treatments for people already suffering from the infection. In response, the US FDA has now granted five emergency use authorisations to experimental therapies; drugs from Regeneron and Eli Lilly became the latest recipients last week.
Despite this progress, it is clear that big pharma considers the search for potential treatments far from over. This morning Merck & Co announced the $425m buyout of Oncoimmune’s lead Covid-19 therapy, a recombinant fusion protein that generated very encouraging data in an early look at an ongoing phase III trial.
The interim analysis – conducted on 75% of the trial’s 270 participants – found that severe or critically ill patients treated with CD24Fc had a 60% higher chance of achieving clinical recovery than those in the placebo group (p=0.005). The median time to recovery was 6 days for CD24Fc patients compared with 10 days in the placebo group, while the risk of death or respiratory failure was cut by more than 50%.
Final results from the Oncoimmune phase III trial are expected by the end of the year, and Merck is presumably hoping to see a clear signal of a mortality benefit. Only dexamethasone has achieved this so far: in the Recovery trial the generic steroid cut deaths by 35% in ventilated patients and by 20% in those receiving oxygen.
Merck told Evaluate Vantage that it was “too early to speculate” whether the trial might be sufficient to support an EUA application. However, it seems likely that this is the hope. The spanner in the works could be Oncoimmune’s manufacturing capacity – being able to manufacture at scale is a requirement of any regulatory approval – thus the decision to sell up to a large partner with deep pockets and expertise to oversee a quick ramp-up makes sense.
Oncoimmune should certainly be applauded for making the most of this opportunity. The $425m fee is all about CD24Fc: Oncoimmune’s other assets are being spun out into a new entity, which will be owned by the company’s existing shareholders, and in which Merck will buy a $50m stake.
|FDA emergency use authorisations for Covid-19 so far|
|Date||Product (company)||Setting||Ongoing or confirmatory trials|
|Nov 20||Casirivimab and imdevimab (Regn-COV2; Regeneron)||Patients with mild-to-moderate disease at high risk of progressing to severe Covid-19 and hospitalisation||Subcutaneous formulation; prevention; confirmatory in mild to moderate; hospitalised.|
|Nov 19||Olumiant (Lilly) in combination with Veklury (Gilead)||Hospitalised patients requiring oxygen, ventilation or ECMO||Hospitalised patients (monotherapy); Tacit-R (academic trial); ACTT-4 (+Veklury, yet to start)|
|Nov 9||Bamlanivimab (Lilly)||Patients with mild-to-moderate disease at high risk of progressing to severe Covid-19 and hospitalisation||Prevention study (Blaze-2); + LY-CoV555, mild to moderate|
|Aug 23||Convalescent plasma (various providers)||Hospitalised patients||-|
|May 1||Veklury (Gilead)||Certain hospitalised patients||Outpatient setting; paediatric trial|
|Source: FDA, clinicaltrials.gov.|
Interestingly, the primary thrust of CD24Fc’s clinical development was graft-versus-host disease, before the pandemic prompted a pivot. Another GvHD treatment, Incyte and Novartis’s Jak inhibitor Jakafi, is also being trialled in hospitalised Covid-19 patients; an Incyte-sponsored study is explicitly striving to demonstrate a mortality benefit.
And of course Olumiant, one of the EUA’s issued by the FDA last week, is another Incyte Jak inhibitor, albeit sold for rheumatoid arthritis by Lilly. The Covid-19 approval was on the back of the NIH-funded trial ACTT-2, which found that adding Olumiant to Veklury sliced a day off median time to recovery, over Veklury monotherapy.
In real terms this was eight versus seven days respectively; a hazard ratio of 1.15 and 95% confidence interval of (1.00, 1.31) “indicated a statistically significant effect”, the FDA said. Other measures, including odds of clinical improvement and patient progression also favoured the combination arm, while 29-day mortality was 4.7% for Olumiant plus Veklury versus 7.1% for placebo plus Veklury.
If these results seem underwhelming, a Lilly-sponsored trial should show more clearly what Olumiant is capable of here, and help tease out exactly what the Gilead antiviral is contributing.
Regeneron too is running several confirmatory studies with Regn-Cov2, a combo of casirivimab and imdevimab that also just won an EUA on the back of data that still leave room for improvement.
Approval was granted on results in 799 non-hospitalised patients with mild-to-moderate disease, showing that viral load reduction was larger in patients treated with the antibody combo than those on placebo, at day seven. Most important, the agency stated, were data on a secondary endpoint of hospitalisations and emergency room visits; these medical visits occurred in 3% of the treated group and 9% of placebo-treated patients.
Sales forecasts for Regn-Cov2 show that the financial community expects better treatments to come along – and for the vaccine rollout to diminish need, of course. With big pharma willing to jump in on projects like CD24Fc, hopefully this greater efficacy is not too far behind.