GSK’s tribulations continue
Two days ago GSK canned lete-cel. Now it is ditching otilimab, and daprodustat’s future is looking dicey.
GSK seems to be having a pretty wretched time. This morning the group said that the mediocre performance of the rheumatoid arthritis project otilimab in its pivotal trials meant that the project would have to be shelved. This is a huge disappointment; last summer GSK had insisted that the antibody could bring in peak sales northwards of £1bn ($1.16bn).
Separately, the anaemia project Duvroq got a mixed verdict from an FDA adcom. At least the panel gave its backing to the use of the pill in severely ill patients – but the agency itself has knocked back similar agents, and approval even in this population is by no means assured.
Contrasting outcomes
Otilimab hit in two of the three studies making up the pivotal Contrast programme – but not emphatically enough. Contrast-1 and Contrast-2 met the primary endpoint – this is ACR20 response at week 12 for all three Contrast trials – but did not show an strong enough effect over placebo to “transform patient care”. The third trial was an outright failure.
| GSK's Contrast phase 3 programme for otilimab in moderate to severe RA | ||
|---|---|---|
| Trial | Details | Outcome |
| Contrast 1 | 1,500 pts with inadequate response to methotrexate. Tested otilimab vs placebo/Xeljanz against a background of methotrexate and folic/folinic acid | Hit, but not well enough |
| Contrast 2 | 1,700 pts with inadequate response to Dmards. Tested otilimab vs placebo/Xeljanz against a background of Dmards | Hit, but not well enough |
| Contrast 3 | 550 pts with inadequate response to biologic Dmards and/or Jaks. Tested otilimab vs placebo/Kevzara against a background of Dmards. | Missed |
The limited efficacy of the anti-GM-CSF MAb does not justify its continued development, GSK said. Full results from the Contrast programme ought to emerge next year.
GSK licensed otilimab from Morphosys in 2013 for all therapeutic uses, paying €22.5m ($22.5m). As late as last June GSK was still very happy with the asset, saying that otilimab’s sales could peak at £1-2bn, though the sellside’s numbers, compiled by Evaluate Pharma, were somewhat lower. Now investors must contend with another discontinuation, hard on the heels of GSK’s abandonment of its NY-ESO-1-targeting projects on Tuesday.
Yes… and no
The other letdown GSK conceded today concerns Duvroq (daprodustat), its HIF-PH inhibitor for anaemia in chronic kidney disease. The FDA panel assessing the pill determined that it was good enough to be approved for use in adults who need dialysis to manage their condition, but not in patients who are not dialysis-dependent.
Approval in the latter population was always going to be a long shot, and now the chances are slimmer still. Even in dialysis-dependent patients approval cannot be considered in any way assured; the FDA is wary of this class, dishing out complete response letters to both Astrazeneca/Fibrogen’s roxadustat and Akebia’s vadadustat this year.
It might be unwise to rule out a CRL for Duvroq too – or at least the mandating of another trial. The project has a Pdufa date of February 1, 2023, and is also awaiting a European verdict, probably in the first half of next year.
All in all this week’s news highlights the precarity of GSK’s pipeline. The biggest of its remaining hopes is surely its RSV vaccine, RSVPreF3 OA, also known as GSK3844766A. Pivotal data presented at this month’s IDWeek meeting suggested the jab has slightly better efficacy than Pfizer’s rival, RSVpreF (PF-06928316).
Unfortunately for GSK, though, Pfizer’s vaccine looks safer. The placebo-adjusted rates for any systemic adverse event were 1.7% and 17.5% for Pfizer’s and GSK’s shots respectively. Pfizer’s project also had lower rates of injection site pain, fatigue, headache and muscle pain.
SVB analysts interpreted the tolerability stats as clearly advantageous for Pfizer, though they added that the toxicity of GSK’s jab was not worse than successful older adult vaccines like Prevnar and Shingrix.
With otilimab and lete-cel going nowhere, the RSV jab will have to perform commercially as well as clinically. Investors will be in no mood for yet another disappointment.
