Roche races to regulators after matching AstraZeneca's rare disease blockbuster in phase 3

Roche is ready to wade into the increasingly ferocious fight for the paroxysmal nocturnal hemoglobinuria (PNH) space. The Big Pharma’s subcutaneous contender matched AstraZeneca’s intravenous blockbuster incumbent Soliris in phase 3, positioning it to file for regulatory approvals around the world.

Alexion, now part of AstraZeneca, has dominated the PNH market for years, racking up billions of dollars in sales of the anti-C5 monoclonal antibodies Soliris and Ultomiris in the process, but a drove of drug developers are working to unseat the incumbents. Apellis Pharmaceuticals won approval of Empaveli in 2021, Novartis will submit iptacopan to regulators this year and Alnylam and Regeneron are in phase 3.

Seeking to carve out a piece of the market, Roche is running three phase 3 trials of its anti-C5 recycling monoclonal antibody crovalimab. The drugmaker's Genentech unit reported top-line data from one of the studies, COMMODORE 2, on Tuesday.

Roche designed COMMODORE 2 to compare crovalimab, given as a subcutaneous injection every four weeks, to intravenous doses of Soliris every two weeks in around 200 PNH patients who hadn’t previously received complement inhibitors. The co-primary endpoints looked at transfusion avoidance and control of the ongoing destruction of red blood cells after 25 weeks.

The clinical trial met the co-primary endpoints. Roche said crovalimab achieved disease control and was noninferior to Soliris but is yet to share any data from the study. The Big Pharma is holding back the data reveal for an upcoming medical meeting. 

Using the results, plus data from an ongoing open-label phase 3 study, Roche plans to seek approval for crovalimab around the world. The impact Roche has on the market will depend on the as yet unrevealed data from the phase 3 study. 

The route of administration and dosing schedule gives crovalimab an advantage over Soliris, but the case for the Roche drug over other contenders is less clear-cut. AstraZeneca’s Ultomiris is given intravenously every eight weeks, and Apellis’ Empaveli is administered subcutaneously, albeit twice weekly using an infusion pump. Novartis’ iptacopan is taken orally twice a day and beat AstraZeneca’s drugs in phase 3.

AstraZeneca is working to defend its fiefdom, too, hustling a pair of factor D candidates through the clinic to strengthen its hand in the face of mounting competition. Talking to Fierce Biotech last year, Anita Hill, M.D., Ph.D., Alexion’s global medical affairs lead for hematology and nephrology, said, “Factor D will be an easier target, potentially, to maintain that sustained complement inhibition that patients with PNH really need to avoid devastating complications.”