Roche Drug for Rare Blood Disorder Hits Phase 3 Goals; Regulatory Filings Are Next

A Roche drug in development for treating a rare blood disorder has Phase 3 data showing it worked at least as well as a blockbuster AstraZeneca drug while also offering patients a dosing advantage. With those results in hand, the Swiss drugmaker says it is now planning to seek regulatory approvals worldwide.

Roche’s crovalimab is a potential treatment for paroxysmal nocturnal hemoglobinuria (PNH), a disorder in which the complement system, a part of the immune system, attacks red blood cells. PNH can lead to anemia and organ damage, among other problems. Standard treatments for PNH include two infused AstraZeneca drugs: Soliris, dosed every two weeks, and Ultomiris, administered every four weeks. Both of them are antibodies designed to block the C5 complement system protein.

Crovalimab, also a C5 inhibitor, is administered as a subcutaneous injection. According to Roche, the drug is engineered to be recycled within the blood circulation, which enables it to sustain its complement system-blocking activity with dosing needed only every four weeks.

The pivotal study is an open-label clinical trial that enrolled about 200 PNH patients who had not previously been treated with a complement inhibitor such as the AstraZeneca drugs. The adults were randomly assigned to receive crovalimab every four weeks or Soliris every two weeks. Study participants younger than 18 were included in an arm treated with crovalimab every four weeks.

Roche said the study met the two main goals of controlling the ongoing destruction of red blood cells and avoiding the need for blood transfusions. A separate open-label Phase 3 clinical trial enrolled patients who switched over from currently approved C5 inhibitors. Roche said results from this test supports the favorable risk-benefit profile observed in the other pivotal study. Without offering specifics, Roche said the data showed its drug achieved disease control and was not inferior to Soliris. The pharma giant said results from both studies will be presented at a future medical meeting. In the meantime, the company is preparing for regulatory submissions around the world.

“People with PNH may benefit from more options to achieve robust disease control with less frequent treatment intervals,” Chief Medical Officer and Head of Global Product Development Levi Garraway said in a prepared statement. “As the first global Phase 3 data for crovalimab, these results emphasize its potential to address these needs.”

PNH was once a rare disease with no approved therapeutic options. The market for PNH drugs is now growing crowded. Soliris’s 2007 approval made it the first therapy for the disorder. That drug and successor Ultomiris became blockbusters under Alexion Pharmaceuticals, the biotech that developed them. AstraZeneca acquired Alexion in a $39 billion deal two years ago, making the company its rare disease unit.

Other companies have emerged to try and steal market share from AstraZeneca. Apellis Pharmaceuticals’ Empaveli, a twice-weekly infused peptide drug that blocks a complement protein called C3, received FDA approval in PNH in 2021. Novartis aims to offer more convenient dosing than the rest of the PNH therapy field with iptacopan, a twice-daily pill. During the annual meeting of the American Society of Hematology (ASH) in December, Novartis presented data showing its small molecule, iptacopan, bested both AstraZeneca PNH medicines in a head-to-head clinical trial. The pharma giant is preparing to file for regulatory approvals in PNH this year.

AstraZeneca won’t cede PNH market share without a fight. The company is developing its own pills for the rare disorder. Vemircopan and danicopan are both oral small molecule drugs designed to block the complement system enzyme factor D. During the ASH meeting, AstraZeneca presented interim Phase 2 results showing twice-daily vemircopan led to control of the disease’s destruction of red blood cells.

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