Oral inhibitor rilzabrutinib granted FDA orphan drug status for SCD
Investigational drug aims to prevent painful crises in patients
The U.S. Food and Drug Administration has granted orphan drug status to Sanofi’s rilzabrutinib, an investigational therapy aimed at preventing painful vaso-occlusive crises (VOCs) in people with sickle cell disease (SCD).
This designation intends to encourage companies to develop therapies for rare diseases, or those affecting fewer than 200,000 people in the U.S. It provides several incentives, such as exemption from certain fees, tax credits for clinical trials, and seven years of market exclusivity if the investigational therapy is eventually approved.
Rilzabrutinib is being tested in a Phase 3 clinical trial called LIBRA (NCT06975865), which is expected to enroll up to 192 SCD patients, ages 10 to 65, who have experienced between two and 10 VOCs in the previous year. The trial is recruiting participants at two sites, one in the U.S. in Florida and the other in London.
“Orphan drug designation for rilzabrutinib reinforces our continued dedication to developing medicines to address the unmet medical needs of people living with rare diseases,” Karin Knobe, MD, PhD, Sanofi’s global head of development for rare diseases, said in a company press release.
Rilzabrutinib blocks activity of key enzyme
A rare genetic disorder, SCD occurs when red blood cells adopt a sickle-like shape that makes them prone to get stuck inside small blood vessels, blocking blood flow and depriving tissues of oxygen. This triggers an inflammatory response that can lead to painful VOCs, as well as other health problems.
“People with sickle cell disease often live with severe episodes of pain from vaso-occlusive crises and other complications that can significantly impact both quality of life and life expectancy,” Knobe said. “There remains a need for novel treatment approaches to address these experiences by modulating the immune system responses that can contribute to sickle cell disease [development].”
Developed using Sanofi’s tailored covalency technology, rilzabrutinib is an oral small molecule designed to block the activity of Bruton’s tyrosine kinase (BTK), while potentially reducing the risk of off-target side effects. BTK is an enzyme that plays a role in immune cell activation and inflammation. By inhibiting BTK, the candidate therapy is expected to ease inflammation and prevent VOCs in SCD patients.
In an SCD mouse model, rilzabrutinib reduced VOCs and markers of inflammation through multiple mechanisms of action.
Patients who complete Phase 3 can enroll in extension
Sanofi launched the Phase 3 LIBRA trial to assess the impact of rilzabrutinib in people with SCD who experience recurrent VOCs.
Eligible participants include those who are not being treated with hydroxyurea and/or L-glutamine (sold as Endari) and do not plan to receive them during the study or those who have been treated with these therapies for at least six months. Participants on hydroxyurea and/or L-glutamine must have been on a stable weight-based dose for at least three months, with plans to continue treatment throughout the study.
In the first part of LIBRA, participants will be randomly assigned to receive either rilzabrutinib or a placebo for one year. Those who complete this part of the study can then enroll in an open-label, long-term extension period, in which all participants will receive rilzabrutinib.
The study’s primary goal is to assess the therapy’s ability to reduce the annualized rate of VOCs after one year of treatment.
In addition to tolerance and safety, secondary study goals include assessing the time to first VOC, the rate of clinic visits due to SCD-related complications, and the rate of home-managed VOCs as reported in a diary. Changes in measures of fatigue, the need for blood transfusions, the number of days requiring pain medication, and the levels of hemoglobin (the protein in red blood cells that carries oxygen) will also be assessed.
Rilzabrutinib has also received orphan drug designation for three other indications: immune thrombocytopenia in the U.S., the European Union, and Japan; warm autoimmune hemolytic anemia in the U.S. and the EU; and IgG4-related disease in the U.S.
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