ASH: Sanofi eyes FDA filing as orphan blood drug hits late-phase goal

A phase 3 trial of Sanofi’s rare blood disease drug sutimlimab has met its primary endpoint. More than half of the participants met the primary endpoint, teeing Sanofi up to file for FDA approval of the complement C1s inhibitor.

Sanofi is developing sutimlimab for use in cold agglutinin disease (CAD), a rare condition in which the immune system turns on the patient’s red blood cells. By inhibiting C1s, Sanofi thinks sutimlimab can prevent the activation of a mechanism that destroys red blood cells, thereby sparing patients from the anemia, fatigue and other symptoms that characterize CAD.

At the American Society of Hematology annual meeting, Sanofi revealed the phase 3 trial generated data to support that hypothesis. After receiving weekly infusions of the study drug for 26 weeks, 13 of the 24 people in the study had met the primary endpoint, a composite assessment that looked at hemoglobin and freedom from transfusions.

Close to two-thirds of participants met the hemoglobin part of the endpoint, indicating they either experienced a 2 g/dL increase from baseline or ended the study with 12 g/dL or higher, a level that is at the bottom of the normal range for women and just below it for men. More than two-thirds of the subjects were free from transfusions from week five onward.

Sanofi, echoing the findings of an earlier study, showed that sutimlimab starts working quickly. The participants experienced a mean increase in hemoglobin of more than 1 g/dL by the end of the first week, rising to more than 2 g/dL by the third week. Hemoglobin levels stayed above 11 g/dL, having begun below 9 g/dL, for the rest of the trial.

The trial also linked sutimlimab to fast-onset effects against other endpoints. Bilirubin, a biomarker for red blood cell destruction, fell in the first week and normalized by week three. Participants also reported improved scores on a fatigue scale from week one onward, suggesting reduced destruction of red blood cells translates into improved quality of life for patients.

Almost all of the patients experienced a treatment-emergent adverse event. Seven people suffered a  treatment-emergent serious adverse event, but none were deemed to be related to sutimlimab. None of the patients contracted meningococcal infections. Other complement inhibitors, such as Alexion’s Soliris, are associated with an increased risk of meningococcal disease.

Sanofi thinks the safety and efficacy data are strong enough to support a filing for approval. A filing in the U.S. is planned for the “near future,” after which Sanofi will approach other regulatory agencies.

Winning approval for sutimlimab will give Sanofi a chance to start recouping some more of the $11.6 billion (€10.5 billion) it spent to acquire Bioverativ last year. Bioverativ acquired sutimlimab the year before being bought by Sanofi, paying $400 million upfront for True North Therapeutics. At the time of Sanofi’s takeover of Bioverativ, Citi analyst Peter Verdult saw sutimlimab as “the most promising pipeline asset” at the acquired company.

The interest in sutimlimab is, in part, a reflection of its potential in indications beyond CAD. Sanofi is running an early phase trial in immune thrombocytopenic purpura.