Precision pays off for Prometheus
Strong mid-stage data defy doubts following rival Pfizer’s spin off.
When Pfizer spun off its anti-TL1A MAb PF-06480605 last week, investors in Prometheus could have been forgiven for feeling jittery. The smaller group’s lead asset, PRA023, also hits TL1A and Pfizer’s move was seen by some as a lack of faith in the mechanism.
Today those jitters were banished by impressive phase 2 data with PRA023 in ulcerative colitis and Crohn’s disease. Notably, Prometheus’s project outperformed the expectations set before the readout, raising hopes that the asset could be best-in-class – and sending the group’s shares rocketing as much as 200% this morning.
The more important of the trials was the placebo-controlled Artemis-UC in ulcerative colitis. The company reported data from the first cohort in this study today. Here analysts had hoped to see a 15%-plus delta versus placebo on clinical remission, the primary endpoint, and a 25%-plus delta on endoscopic improvement (Prometheus takes on Pfizer in inflammatory bowel diseases, September 15, 2022).
The study exceeded this goal, with a difference of 25% on clinical remission and 31% on endoscopic improvement.
The very low placebo response could raise eyebrows, but even so the results put PRA023 in line with Abbvie’s Jak inhibitor Rinvoq, which in phase 3 showed placebo-adjusted remission rates of 22-29%, and endoscopic improvement rates of 29-35%.
And PRA023 does not appear to have the toxicity concerns of the Jaks: Artemis-UC did not find anything alarming in terms of adverse events.
As Prometheus’s chief executive, Mark McKenna, put it during a conference call today: “This is Rinvoq-like efficacy with Entyvio-like safety.”
Whether Pfizer's PF-06480605 – now known as RVT-3101 and being taken forward by a new “Vant” subsidiary – can pull off something similar is the next question. Prometheus has long contended that its project is superior, and this will be put to the test with data from the Tuscany-2 study of RVT-3101, due in the first half of 2023.
Prometheus has taken a different approach to Pfizer, with a biomarker-based strategy. While cohort one of Artemis-UC enrolled all comers, a second cohort comprising TL1A-positive patients is due to yield data in the second quarter of 2023.
The signs from cohort one are promising, with a greater clinical remission rate seen in the subgroup of patients testing positive on Prometheus’s companion diagnostic. The company conceded that patient numbers were limited, however.
Today’s second PRA023 readout came from the uncontrolled Apollo-CD study in Crohn’s disease. Here, analysts had hoped for a 25% or greater rate of both clinical remission and endoscopic response. And again, the trial surpassed this, with 49.1% of patients achieving remission, and 26.0% achieving endoscopic response.
While the data are more difficult to interpret owing to the lack of a placebo arm, SVB analysts noted that PRA023 looks competitive with Abbvie’s Skyrizi, which showed placebo-adjusted remission of 21-22% and endoscopic response of 18-28% in phase 3.
Of course, a bigger test for PRA023 awaits in its pivotal studies, which will have the added peril of testing a subcutaneous formulation – both Artemis-UC and Apollo-CD used intravenous drug.
Prometheus was not giving much away about its phase 3 trial design today, but execs said that the group plans to seek a broad indication, so the studies seem unlikely to focus solely on TL1A-positive patients.