Efanesoctocog alfa, now Altuviiio, approved in US for hemophilia A

Sanofi, Sobi win FDA OK for man-made factor VIII therapy

Lindsey Shapiro, PhD avatar

by Lindsey Shapiro, PhD |

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Note: This story was updated Feb. 24, 2023, to correct the secondary headline since there are several other recombinant factor VIII therapies available.  Altuviiio is a first-in-class therapy, but not the first.

Efanesoctocog alfa, Sobi and Sanofi’s first-in-class, long-lasting recombinant or man-made factor VIII (FVIII) replacement therapy, has been approved by the U.S. Food and Drug Administration (FDA) for the treatment of hemophilia A. It will be marketed under the brand name Altuviiio.

The therapy is indicated both for routine prophylaxis (preventive) treatment — to lower the frequency of bleeding episodes — and the on-demand treatment of bleeds in children and adults with hemophilia A. It also is indicated for use in managing bleeds occurring during surgery in these patients.

Altuviiio is a new class of hemophilia A replacement therapy that is designed to offer significant bleed protection with once-weekly dosing. Its recommended dose for routine prophylaxis in patients of all ages is 50 international units per kilogram (IU/kg) of body weight, given once weekly by into-the-vein (intravenous) injection.

“Today’s approval of Altuviiio allows patients and physicians to reimagine living with hemophilia. The high sustained factor activity levels that can be achieved with Altuviiio have the potential to change the hemophilia landscape,” Paul Hudson, Sanofi’s CEO, said in a press release.

“For the first time, with a once-weekly dose, powerful bleed protection is a reality for patients. Significant shifts in treatment paradigms that improve people’s lives, like Altuviiio, are what we have committed to delivering at Sanofi,” Hudson said.

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Altuviiio expected to be available in April for US patients

According to Sanofi, Altuviiio should become available to patients in the U.S. in April. Its annual cost will be similar to that of preventive treatment with Eloctate, another approved hemophilia A therapy also marketed by Sanofi, to ensure that patients have prompt access to the new therapy.

“This approval marks an important clinical advancement for the hemophilia community because we have an option that can achieve higher levels of factor activity with a single simplified weekly dose,” said Lynn Malec, MD, medical director of the Comprehensive Center for Bleeding Disorders, associate investigator at the Versiti Blood Research Institute, and associate professor of medicine and pediatrics at the Medical College of Wisconsin.

“By maintaining high levels of factor activity throughout the week, patients can be confident in the bleed protection Altuviiio offers,” Malec said.

Sanofi also has in place a comprehensive package of patient support services and online resources for Altuviiio that can now be accessed by individuals who are prescribed the medication.

“On behalf of Sobi I’d like to congratulate our co-development partner Sanofi on this great achievement,” Anders Ullman, Sobi’s head of research & development and medical affairs and chief medical officer, said in another press release, adding, “This is a major milestone in our collaboration as we work towards providing access to this important new treatment for people living with haemophilia A around the world.”

Altuviiio, formerly known as BIVV001, is a type of FVIII replacement therapy that aims to provide hemophilia A patients with a version of the blood clotting protein they are missing.

While a number of other FVIII replacement therapies are available on the market, these treatments require frequent dosing — two to three times weekly — when used prophylactically to prevent bleeding episodes.

Originally developed by Bioverativ, Altuviiio is designed to last longer in the bloodstream, allowing for once-weekly dosing.

Consisting of a lab-made version of FVIII and a fragment of von Willebrand Factor (VWF) — another clotting protein — Altuviiio also contains a small protein called XTEN that works to stabilize the therapy and extend its presence in the bloodstream.

The FDA previously granted Altuviiio breakthrough therapy, orphan drug, and fast track designations, all of which were intended to accelerate its development and review.

Sobi and Sanofi, which are now jointly developing Altuviiio, had submitted a regulatory application to the FDA requesting the therapy’s approval. That application was accepted by the regulatory agency and placed under priority review last August, with an expected decision date of Feb 28. The approval ultimately came five days prior to that deadline.

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New trial data supported FDA’s approval of Altuviiio

Clinical trial data illustrating Altuviiio’s safety and effectiveness in hemophilia A patients supported the application.

The Phase 1/2a EXTEN-A (NCT03205163) trial showed that a single dose of Altuviiio safely increased FVIII activity in men with severe hemophilia A, and had a 3–4 times longer half life than Takeda’s Advate, another FVIII replacement therapy.

Then, the open-label Phase 3 XTEND-1 trial (NCT04161495) tested the treatment in 159 patients with severe hemophilia A, ages 12 and older, across 48 centers in 19 countries. In an open-label trial, both researchers and participants know what medications patients are receiving. All participants had previously been treated with other FVIII replacement therapies.

Among the participants, 133 were given efanesoctocog alfa on a preventive regimen of 50 international units per kilogram of body weight (IU/kg), delivered into the bloodstream once weekly for a year. The remaining 26 participants were given 50 IU/kg as an on-demand therapy to control bleeds for six months, followed by a six-month preventive regimen.

Top-line results demonstrated that the trial met its main goal of achieving clinically meaningful reductions in annualized bleeding rates among those in the preventive treatment arm.

Nearly two-thirds of those patients had no recorded bleeds for the entire year, with 93% having fewer than three bleeds, and 80% having no spontaneous bleeds, or bleeds without an obvious cause.

Some patients had participated in a previous study in which they received preventive treatment with other available FVIII replacement therapies. For those patients, bleed rates were significantly reduced with Altuviiio compared with previous therapies, meeting a key secondary trial goal.

Specifically, bleed rates among those patients reached a mean of 0.69 bleeds per year, a statistically significant 77% reduction from a mean of almost three bleeds per year seen with prior therapies.

Altuviiio also was associated with improvements in quality of life and joint health, as well as with reductions in pain intensity relative to prior treatments.

For the first time, with a once-weekly dose, powerful bleed protection is a reality for patients.

The once-weekly dosing regimen was able to successfully maintain FVIII activity levels at least at 40% of normal for most of the week (four days following dosing), dropping to 15% of normal by day seven.

Among those given on-demand treatment, a single injection of Altuviiio resolved 97% of bleeds. For 12 people who underwent surgery during the study, doctors rated bleed control as excellent.

The treatment has been generally well tolerated in clinical studies. Commonly reported side effects included headache, joint pain, and back pain. No patients developed inhibitors, a type of neutralizing antibody against the treatment that could influence its effectiveness.

The Phase 3 XTEND-Kids trial (NCT04759131) evaluated Altuviiio’s safety, efficacy, and pharmacological properties in 67 boys, ages 12 and younger, with severe hemophilia A who have used other FVIII therapies.

Its main goal was to assess the development inhibitors in these young patients with a year of weekly preventive treatment. The trial, which finished last month, also assessed safety and bleed control.

Interim data from the study showed that 23 children receiving Altuviiio once weekly for 26 weeks (about six months) had a mean of 0.5 bleeds per year, and a median annual bleeding rate of zero. Safety findings were similar to those reported in XTEND-1.

Full data from XTEND-Kids will be presented at a future medical meeting, according to Sanofi. When available, final data from XTEND-Kids also is anticipated to support a future application requesting Altuviiio’s approval in the EU.