Disc sets up polycythemia vera challenge but Silence maintains lead

 

The polycythemia vera field is heating up, with Disc Medicine and Silence Therapeutics each advancing next-generation therapies, playing catch-up to Takeda and Protagonist Therapeutics, who won the FDA’s approval last month for Mimrylo.

While recent data from Disc Medicine’s investigational antibody appear competitive in the polycythemia vera space, analysts believe Silence Therapeutics continues to be the player to beat in the race to bring the next PV therapy to market.

Disc’s asset, dubbed DISC-3405, delivered mid-stage data that “look competitive” to Takeda and Protagonist Therapeutics’ recently approved Mimrylo, Jefferies told investors in a Thursday note. However, they added, “We still think [Silence’s] divesiran has shown best-in-class” performance bolstered by a lighter dosing burden.

DISC-3405 is being tested in the ongoing Phase 2 RESTORE-PV trial, with initial results on Thursday demonstrating improvements in hematocrit control, in turn easing symptom burden. In 13 patients who completed 26 weeks of follow-up, DISC-3405 also significantly reduced the need for blood draws, which is the standard treatment for the disease. More than 60% of these patients were phlebotomy-free at 26 weeks, with the treatments declining overall from four at baseline to 0.6 at the end of 26 weeks.

Disc also reported a favorable tolerability profile for the asset, with adverse events consistent with the underlying disease. Injection-site reactions occurred at a “low rate” and were “self-limited,” the biotech added.

Safety was the main goal of the mid-stage trial, with secondary endpoints measuring the therapeutic’s response on a number of different disease outcomes. These data were presented at the Society of Hematologic Oncology meeting in Houston.

“We were impressed by phlebotomy reductions and hematocrit control,” BMO Capital Markets wrote on Thursday, additionally noting DISC-3405’s “corresponding improvement in patient symptoms.” Indeed, 11 of the 13 patients who completed 26-week follow-up saw improvements in blood cancer symptoms, while 92% had lighter fatigue burden, BMO said, citing Disc’s oral presentation at the conference.

The biotech plans to provide more data from RESTORE-PV by the end of the year. DISC-3405 is also being tested for sickle cell disease, for which Phase 1b data are also expected by year-end.

Despite DISC-3405’s strong showing in RESTORE-PV, William Blair—like Jefferies—appears to see Silence as the polycythemia vera frontrunner, pointing to the company’s recent Phase 2 SANRECO readout. Last month, Silence reported that the siRNA therapy divesiran led to an 88% clinical response rate in treated patients, compared with 19% in placebo controls. The trial defined treatment response as the absence of phlebotomy and keeping hematocrit levels below 45% from weeks 18 through 36.

SANRECO’s outcome “is best-in-field for [polycythemia vera] currently,” William Blair told investors in a note on Thursday, adding that Silence’s divesiran “maintains strong differentiation” in the field. More data from SANRECO are expected at the upcoming American Society of Hematology meeting in December, the analysts noted.

The recent approval of Takeda and Protagonist’s Mimrylo, granted late last month, is a “bellwether for the space,” William Blair noted, additionally pointing to the drug’s $218,400 annual price tag, which creates “clear room for pricing upside” for Silence’s divesiran and other upcoming therapies in this space.

https://www.biospace.com/drug-development/disc-sets-up-polycythemia-vera-challenge-but-silence-maintains-lead