The decision was based on a positive recommendation by EMA’s Committee for Medicinal Products for Human Use.
Orphan designation is given to investigative therapies with the potential to be safe and effective for rare, life-threatening, or chronically debilitating conditions that have no approved treatments, or where the potential therapy is showing significant benefit over existing treatments.
These designations are meant to accelerate the treatment’s clinical development and review by providing regulatory support and financial benefits, and to ensure marketing exclusivity for a period of time upon regulatory approval (seven years in the U.S. and 10 years in Europe).
“I am pleased to see the regulatory community recognize the urgent need to bring therapies to people living with sickle cell disease,” Frank Lee, Forma’s president and CEO, said in a press release, noting that “without effective treatment, sickle cell can affect all organs over time and lead to substantial suffering.”
“We embrace the potential this designation may provide as we prepare to initiate a global registrational Phase 2/3 trial with FT-4202 in the first quarter of 2021,” Lee said, in addition to the company’s ongoing and enrolling Phase 1 study.
Earlier this year, FT-4202 was designated an orphan drug, and given fast track and rare pediatric disease designations in the U.S. for the same indication.
FT-4202 is an orally available, small molecule that works by activating an enzyme called pyruvate kinase-R (PKR) in red blood cells. This enzyme naturally lowers the levels of 2,3-diphosphoglycerate (2,3-DPG), a metabolic byproduct that impairs hemoglobin from binding to oxygen, and it increases the levels of adenosine triphosphate (ATP) — cells’ “energy currency.”
As such, FT-4202 is expected to help hemoglobin hold on to oxygen for longer periods, reducing the “sickling” of red blood cells that characterizes SCD. It should also increase energy levels in these blood cells, improving their health and survival.
Results from a preclinical study in mouse models of sickle cell — to be presented at the 62nd American Society of Hematology (ASH) Annual Meeting and Exposition next month — showed that FT-4202 significantly increased hemoglobin levels and its binding ability to oxygen, improving red blood cell survival and easing sickling.
Forma launched a two-part Phase 1 clinical trial (NCT03815695) to evaluate FT-4202’s safety, tolerability, pharmacokinetics (its movement into, through, and out of the body), and pharmacodynamics (its effects on the body) in up to 150 healthy adults and SCD patients.
The study’s first part, now completed, tested single and multiple ascending oral doses of FT-4202 against a placebo in 80 healthy adults: 32 were given single doses of either FT-4202 or a placebo daily, and 48 others given multiple oral FT-4202 or placebo doses, both for 14 days.
Data from this part showed that FT-4202 had a favorable safety, tolerability, and pharmacological profile, with most side effects being mild. The therapy also increased levels of ATP and lowered those of 2,3-DPG in healthy red blood cells, supporting its potential benefits in SCD patients.
The study’s second part in patients, ages 12 to 65, is now open, and enrolling at sites across the U.S. As with the first part, patients here are being randomized to single ascending doses or placebo, and multiple ascending doses or placebo, both for 14 days. A third patient group will also be enrolled for a longer term (12 week) and open-label safety study.
Site and contact information can be found here.
During the ASH meeting, Forma also plans to present data from the first patient groups treated with FT-4202 in the trial, which is expected to end in September 2021. The company will also share details of the future Phase 2/3 PRAISE trial, meant to support the therapy’s approval.
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