Sanofi’s response to nonfatal thrombotic events in a phase 3 hemophilia program has delayed its plans to seek approval for RNAi drug fitusiran by 18 months. The delay will “allow for the appropriate collection and assessment of safety and efficacy data under the amended protocols.”
Thrombotic events emerged as a significant concern for the fitusiran program in 2017 when dosing in a phase 2 trial was paused after a hemophilia A patient died from a blood clot. Alnylam, which ceded control of fitusiran to Sanofi early in 2018, responded to the original clinical hold by introducing new risk-mitigation measures.
Those measures, which included efforts to educate patients and physicians about reduced doses to treat breakthrough bleeds, helped Sanofi wrap up phase 2 and move into pivotal studies in 2018.
Sanofi ran into trouble again in late October when nonfatal thrombotic events in the phase 3 led it to pause dosing. Sanofi is now set to resume dosing in adolescents and adults, but a clinical trial that was giving fitusiran to children aged one to 12 years remains paused. Researchers are continuing to evaluate dosing in the pediatric study.
The resumption of the other trials follows the decision to change the dose and dosing regimen to improve the benefit-risk profile of the treatment for hemophilia A and B. Sanofi’s actions have had a significant impact on the timeline for getting fitusiran to market.
Sanofi held the primary completion for one phase 3 trial late last month. The primary completion for a second phase 3 is set for February. Sanofi designed the trials to show the effect of fitusiran on the annualized bleeding rates of patients with severe hemophilia A and B over an eight-month period.
The change in dose and dosing regimen means Sanofi will need to collect safety and efficacy data under the amended protocols before being in a position to seek approval for fitusiran. A delay of 18 months or so is expected.
Fitusiran was one of the drugs that survived the cull overseen by Paul Hudson when he took over as CEO of Sanofi. The RNAi therapy targets a protein that inhibits blood clotting. Phase 2 data suggested the approach may work in patients with hemophilia A and B, with or without inhibitors, providing a point of differentiation in a competitive space, but safety worries have hung over the program.