Hard data are great for the pharma crowd—and of course needed to seal an FDA approval. But beyond that, Sanofi has been heartened to hear patient stories saying the French company’s hemophilia A treatment helped them achieve a “near normal” status.
Sanofi presented data on its broad bleeding disorder pipeline at the International Society on Thrombosis and Haemostasis 2022 Congress Sunday, showcasing key late-stage data on two therapies: efanesoctocog alfa and fitusiran.
Starting with efanesoctocog alfa, which the company has dubbed internally as Effa, Sanofi demonstrated in the phase 3 XTEND-1 study that once-weekly treatment protected patients who have severe hemophilia A from bleeds, which was the main goal of the trial. The therapy was tested in patients 12 years and older who have severe disease and had previously received factor VIII replacement therapy, which is the standard of care used to prevent joint bleeding and halt deterioration of joints. Roche’s Hemlibra is the market leader for this indication.
Sanofi’s rival helped patients achieve near-normal factor VIII levels, which is a key biomarker in the disease that results from a deficiency of this clotting protein. It also met its secondary endpoints, including superior bleed protection compared to prior factor VIII prophylaxis.
Sanofi’s Tom Snow, global franchise head for Neurology and Rare Blood Disorders, said patients had an annualized bleeding rate of 0.0—"you can't do much better than that.”
The trial featured two arms, one larger group of 133 patients receiving efanesoctocog alfa as prophylaxis once weekly for 52 weeks. The second arm saw 26 patients take efanesoctocog alfa on-demand for 26 weeks before switching to once-weekly prophylaxis for the next 26 weeks.
This design gave Sanofi a broader idea of how efanesoctocog alfa can work in two different patient groups, Snow told Fierce Biotech in an interview.
Results from the on-demand arm showed that 77% of patient had zero bleeds once they switched to efanesoctocog alfa as prophylaxis over the 26-week treatment period.
No new safety signals were revealed in the late-stage study. There were no allergic reactions or anaphylaxis, nor any thrombotic events. There was one death in the trial due to pancreatic cancer, which was not related to the study drug. Common side effects were headache and joint stiffness.
Sanofi is hoping to position efanesoctocog alfa as a med that can improve on standard of care. Patients with hemophilia often have to accept some tradeoffs in their regimen to balance bleed control, efficacy and treatment burden. Some patients switch over to what’s called non-factor treatment, like Hemlibra, to avoid additional treatments, instead of replacement therapy that can be more effective but much more burdensome.
“I think with Effa we're hitting a real sweet spot in terms of basically maximum efficacy with the factor replacement therapy and near normal factor levels,” Snow said.
This is where those patient stories come in. Snow said they have heard from investigators that patients report a “near normal” status for most of the week with just the once-a-week dose.
“So you have this really nice prophylaxis, really nice bleed control and much more manageable in terms of terms of injection frequency,” Snow said of efanesoctocog alfa.
“The things that are really, really exciting to hear patients in the study talking about is it almost brings about a mindset shift,” Snow said. “We had some of the patients in the study saying ‘I feel like I've changed from can't do to can do.’”
But despite all this, efanesoctocog alfa will still emerge onto a market entrenched by Roche’s blockbuster Hemlibra. But Snow, who of course has been watching the impact the rival drug’s 2017 approval has had, believes Sanofi’s therapy can win over patients who may be experiencing breakthrough bleeds, a complication that requires treatments with a factor therapy. There’s also little difference between the dosing regimen of the two treatments.
“The Hemlibra launch and the impact that has had shows that there are still unmet needs within the market,” he said. “We think that there could be a nice opportunity to bring some patients back to factor with what Effa could be able to offer.”
Snow said that Sanofi is “embedded within the hemophilia community” thanks to existing factor treatments like Alprolix and Eloctate, so launching the new med shouldn’t be a problem in terms of reaching patients and physicians.
Sanofi is currently wrapping up preparations for a biologics license application for efanesoctocog alfa and has previously said the med will be filed midyear.
The benefit-risk balance
The French pharma is also touting fitusiran this weekend, a therapy the company hopes could provide an option for hemophilia A and B patients with as few as six injections a year, while still maintaining a high level of efficacy.
In the phase 3 ATLAS- PPX study, fitusiran met the main goal of significantly reducing bleeding episodes compared to prior factor or bypassing agent prophylaxis. As for the fine print, Snow said the therapy helped patients achieve about a 61% reduction in annualized bleed rate compared to prior prophylaxis, 0.0 median annualized bleeding rate compared to 4.4 in the comparison arm, and 63% of patients had zero bleeds.
One challenge with fitusiran has been its safety profile. The drug was sidelined with an FDA clinical hold in 2017 due to incidents of thrombotic events. Snow said the latest ATLAS readout showed safety comparable to the drug’s known profile. The main adverse events were liver enzyme elevations, which normalized after the fact.
But there were two thrombotic events. Snow said one was a “cerebrovascular accident” in a patient who had a history of deep vein thrombosis—a condition that was not previously known when the person entered the trial. Had that condition been known, the patient would have been excluded, Snow said. The second event occured in one of the patient’s eyes, and it’s unknown whether that was related to treatment with fitusiran.
To mitigate these side effects, Sanofi is exploring a lower dose. New patients who enter the late-stage program will receive the new dosing regimen, which Snow said should “further optimize the benefit-risk of this compound.”
Thromboembolic events are a known complication of hemophilia treatment, according to Snow. So companies testing drugs in this therapeutic area are always on the lookout for this adverse event. Sanofi will need to see data from the lower dose studies to see how efficacy holds up for fitusiran, but Snow isn’t too worried.
The therapy is further out from regulators that efanesoctocog alfa is. Sanofi is in discussions with regulators about an eventual submission, but Snow says the application likely won’t be filed until 2023.
So Sanofi has two blood disorder treatments inching closer to regulators: efanesoctocog alfa for hemophilia A and fitusiran for hemophilia A and B. But besides that obvious difference, how will the therapies work together in Sanofi’s stable of medicines? Snow said they address different patient segments, even within the hemophilia A indication.
“We really see kind of different segments in the markets emerging. One is a group of patients who really wants maximum efficacy. They want to live as quote-unquote, ‘normal a life as possible,’ not have to worry about bleeds, etc.” Snow said. These patients are good candidates for efanesoctocog alfa.
Fitusiran, meanwhile, is a better fit for patients seeking extended efficacy with a lower treatment burden and number of required injections.