Arena Pharmaceuticals has posted positive data from a phase 2 trial of its pulmonary arterial hypertension (PAH) candidate ralinepag. The trial linked ralinepag to improvements in pulmonary vascular resistance (PVR), sending Arena’s stock up 41% and putting it on a path that could lead to a showdown with Johnson & Johnson.
Investigators enrolled 61 adults with PAH who were on a stable treatment regimen and randomized two thirds of them to receive ralinepag. The remaining 21 patients received placebo. Investigators titrated the study drug for nine weeks, after which a 13-week treatment period began. At the end of this period investigators measured the participants’ PVR and 6-minute walk distances and compared them to baseline.
The trial recorded a statistically-significant decline in PVR. Median PVR in the ralinepag arm fell by 163.9 dyn.s.cm-5 from its starting point of 705 dyn.s.cm-5. The number for the placebo arm ticked up slightly, although participants in that cohort had a lower median PVR of 480 dyn.s.cm-5 going into the trial.
Differences in the baseline characteristics of the patients and less impressive six-minute walk data could indicate ralinepag will find it harder to move the needle in phase 3. But for now Arena is celebrating a success after a tough few years.
“We see ralinepag as a potential best-in class oral prostacyclin receptor agonist with the potential to replace selexipag in its place in the therapeutic paradigm,” Arena CMO Preston Klassen, M.D. said.
Selexipag, sold under the brand name Uptravi, is one of the drugs J&J gained in its $30 billion acquisition of Actelion. Uptravi won FDA approval in 2015, racked up sales of about $250 million in its first year on the market and is central to J&J’s attempt to drive growth by making PAH its sixth therapeutic area.
Klassen thinks data generated to date, albeit from separate studies, suggests ralinepag has an edge over Uptravi in some regards.
“Oral selexipag, a small molecule prostacyclin receptor agonist, acts via an active metabolite with a shorter half-life and larger peak to trough fluctuations than ralinepag,” he said.
Arena is now gearing up to talk to regulators about a phase 3 trial it hopes will deliver data to derail J&J’s plans and get its own business back on track.
Data from the 6-minute walk test raise doubts about the prospects of ralinepag in phase 3, though. The trial failed to show a statistically-significant increase in the distance walked by patients in the treatment arm.
Participants started out walking a mean of 393 meters in six minutes. This increased by 36.2 meters by the end of the trial. The numbers for the placebo arm were 351 meters and 29.4 meters. During its clinical trial program, Uptravi recorded a treatment effect of 12 meters on the walking distances of PAH patients.
Arena thinks its data are clinically significant, though, and downplayed the importance of the failure to clear the statistical hurdle.
“As this was a small clinical study, and the power of the statistical testing was focused on the primary PVR endpoint, the study was not powered to detect a statistically significant difference between treatment groups in 6MWD. We are very encouraged by the magnitude of the increase in 6MWD seen with ralinepag and are investigating factors that may have impacted the effect seen in the placebo control group,” Klassen said.
The true importance of the finding will likely only emerge as ralinepag advances. But for now the dataset as a whole represents a boon for Arena at a time when it is trying to regain its footing under the leadership of Amit Munshi.
Having seen obesity drug Belviq flop, Arena hired Munshi to engineer a turnaround. Since then, Arena has slashed its headcount and bet its future on its clinical-phase pipeline. The successful phase 2 trial of the internally-discovered ralinepag means Arena 2.0 is off to a good start.