Oral Oxbryta Safe, Effective Over Long Term and in Real World

Marta Figueiredo, PhD avatar

by Marta Figueiredo, PhD |

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Long-term treatment with Oxbryta (voxelotor) safely and effectively reduced anemia and red blood cell destruction (hemolysis), while keeping a low rate of painful vaso-occlusive crises (VOCs), in adolescents and adults with sickle cell disease (SCD).

That’s according to nearly three years of data from the Phase 3 HOPE trial and its extension study.

These findings, along with real-world data consistent with those of HOPE (NCT03036813), will be presented by Global Blood Therapeutics (GBT), the therapy’s developer, through three posters at the 2021 American Society of Hematology (ASH) Annual Meeting & Exposition, slated for Dec. 11–14. ASH’s 63rd annual meeting will be held both online and in-person, at the Georgia World Congress Center, in Atlanta.

“Our data presentations at ASH 2021 include three new analyses from the growing body of data on Oxbryta that reinforce our belief in the benefits of this innovative and potentially disease-modifying treatment for sickle cell disease,” Kim Smith-Whitley, MD, GBT’s executive vice president and head of research and development, said in a press release.

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Oxbryta is a first-in-class oral therapy that targets SCD’s underlying cause by increasing the ability of hemoglobin — the protein inside red blood cells that’s responsible for transporting oxygen —  to bind oxygen. It thereby prevents hemoglobin clumping and the resulting red blood cell sickling and destruction that characterize SCD.

The therapy is available in the U.S. for adults and children with SCD, ages 12 and older, and is currently under review by regulators in Europe for the same indication.

A potential label expansion to include children as young as 4 is being evaluated by the U.S. Food and Drug Administration under priority review; a final decision is expected no later than Dec. 25.

Regulatory applications were mostly based on six-month data from the global HOPE trial, which evaluated nearly 1.5 years of daily treatment with Oxbryta (900 or 1,500 mg capsules) against a placebo in 274 SCD patients, ages 12–65.

Consistent with those at six months, the final 1.5-year results showed that the therapy, at its now-approved dose of 1,500 mg, led to rapid, significant, and sustained increases in hemoglobin levels, while reducing hemolysis and VOCs, and improving patients’ overall health.

After completing HOPE, participants could choose to enroll in its open-label extension (OLE) study (NCT03573882), in which all would receive 1,500 mg of Oxbryta for up to five years or until they gained access to the therapy through commercialization or a managed access program.

In the poster to be presented at the meeting, titled “Long-Term Safety and Efficacy of Voxelotor for Patients with Sickle Cell Disease: Results from an Open-Label Extension of the Phase 3 HOPE Trial,” researchers will share up to nearly three years of combined data from HOPE and its OLE.

Of the 199 patients who completed HOPE, 178 (89.4%) enrolled and were dosed in the OLE study. Their median age at OLE enrollment was 25 years, and most (84.3%) were adults, while 15.7% were adolescents.

As of Dec. 31, 2020, participants had received Oxbryta for a median of 69.9 weeks, or about 17 months, and up to nearly two years. A total of 78 patients (43.8%) were treated for at least 72 weeks (nearly 1.5 years), and 52 of them had previously received Oxbryta in HOPE, for a combined exposure duration of at least 144 weeks (nearly three years).

Results showed that Oxbryta’s benefits were sustained over the longer-term in patients originally assigned to the therapy. Additionally, patients switching from a placebo saw a reduction in their anemia (low hemoglobin levels) and hemolysis with Oxbryta.

Benefits observed in placebo-to-Oxbryta patients were similar to those previously observed in HOPE for those given Oxbryta. Also, patients experienced few VOCs per year, with an annualized rate of 1.3.

The therapy’s safety profile with longer-term treatment also was consistent with that reported in the HOPE trial, with no new safety concerns identified. Most SCD-unrelated adverse events were mild to moderate in severity and most often comprised joint pain, headache, pain, nausea, and pain in the fingers and toes. Treatment discontinuation due to adverse events (side effects) occurred in 11 patients (6.2%).

“Long-term use of [Oxbryta] is safe, well tolerated, and effective in reducing anemia and hemolysis, with a low rate of VOCs, in patients with SCD,” the researchers wrote.

Real-world setting

Findings from real-world practice also support Oxbryta’s therapeutic benefits. Data collected from the Symphony Health claims database, involving nearly 2,700 SCD patients who took the therapy in a real-world setting, are consistent with the results from the HOPE study, according to GBT’s Smith-Whitley.

In a poster titled “Real-World Experience of Voxelotor for the Management of Complications in Sickle Cell Disease,” researchers will share data from these patients, ages 12 and older, who started Oxbryta treatment between November 2019 and March 2021. The patients’ mean age was 34.6 and 60% were female.

“The Symphony Health claims analysis is an ongoing evaluation of the real-world experience with Oxbryta among patients across the United States and one of the largest studies of a medicine for sickle cell disease,” Smith-Whitley said in an emailed statement to Sickle Cell Disease News.

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Results showed the therapy raised hemoglobin levels by a degree consistent with increases seen in the HOPE study and led to significant reductions in blood transfusions (by 43%), VOCs (by 22%), and all-cause and VOC-related hospitalizations (by 32–36%).

“These are important clinical benefits,” Smith-Whitley said, adding that “this large real-world analysis further validates the role of Oxbryta as a potential disease-modifying therapy for sickle cell disease.”

Initial real-world results from RETRO (NCT04930328), a multicenter, post-marketing, retrospective study of about 300 SCD patients, ages 12 and older, from 10 U.S. study sites, will be presented in the poster “Real-World Experience of Patients with Sickle Cell Disease Treated with Voxelotor: A Multicenter, Retrospective Study.”

The interim analysis included data on 45 patients (mean age of 34.3) whose medical records — one year before Oxbryta and up to one year after treatment — were entered at five sites at the time of data cutoff (June 25). Mean treatment duration was 48.1 weeks (about 11 months) and the initial prescribed dose was most often 1,500 mg (77.6%).

Available data showed that Oxbryta was associated with rises in hemoglobin levels and drops in markers of hemolysis, and that its safety was consistent with that reported in the HOPE study.

“Further evaluation is needed, with additional data from all 10 sites, and will be presented later,” the researchers wrote. That study is being supported by GBT.