FDA Approves Two Gene Therapies for Sickle Cell, First CRISPR-Based Medicine

FDA Entrance_iStock, Grandbrothers

Pictured: FDA headquarters/iStock, Grandbrothers

Following in the footsteps of its U.K. counterpart, the FDA on Friday approved the first-ever CRISPR-based gene editing therapy in the form of Vertex Pharmaceuticals and CRISPR Therapeutics’ Casgevy (exagamglogene autotemcel) for sickle cell disease, while also granting approval to bluebird bio’s lovo-cel, which will carry the branded name Lyfgenia.

Casgevy has been hailed as a potentially curative treatment for the approximately 100,000 Americans with sickle cell disease (SCD), a disorder caused by a mutation in the genes involved in producing hemoglobin beta, an iron-rich compound found in red blood cells (RBC). This results in some RBC being shaped like “sickles” and becoming sticky, slowing or blocking blood flow while leading to anemia and episodes of extreme pain, sometimes called vaso-occlusive events. Casgevy is specifically approved to treat SCD patients 12 years and older with recurrent vaso-occlusive crises.

Casgevy uses the Nobel prize-winning technology CRISPR/Cas9 gene editing system discovered more than a decade ago by Jennifer Doudna and Emmanuelle Charpentier to edit a patient’s hematopoietic stem cells to produce high levels of fetal hemoglobin.

Friday’s approval for Vertex and CRISPR is based on data from a pivotal Phase I/II/III trial and a long-term safety and efficacy study, which together demonstrated that Casgevy could significantly lessen severe vaso-occlusive events and hospitalizations.

Bluebird bio’s Lyfgenia, a lentiviral gene therapy, delivers a functional copy of the hemoglobin beta gene directly into a patient’s hematopoietic stem cells. In a single arm, 24-month study, 28 patients of 32 patients treated with Lyfgenia achieved complete resolution of vaso-occlusive events.

In an interview with BioSpace, Martin Steinberg, a hematologist at Boston University and a member of Vertex’s exa-cel steering committee, called the results of both of these trials “spectacular.”

“I don’t think that any of us thought that they were going to be as good as they are,” Steinberg said. “We thought they would work, but to cure—at least in the short term—virtually everybody, I don’t think we expected that.”

Eric Kmiec, founder and executive director of the ChristianaCare Gene Editing Institute, echoed this sentiment in a statement sent to BioSpace ahead of the anticipated approvals. “As scientists, the fact that we have arrived at a potential curative treatment for sickle cell disease in a relatively brief period is a testament to the power of resolute researchers in this field who have never stopped,” he said.

“The challenge, however, is the very people we want to help may not be able to get access to or afford the million-dollar treatment and the length of time it will take to be treated—weeks and weeks in the hospital,” Kmiec added. “The numbers of people who can be treated are limited. We must work with the health care industry and pharmaceutical companies who will market, produce and deliver the treatments to make sure that all people can get access.” 

In a statement to BioSpace, Tim Hunt, CEO of the Alliance for Regenerative Medicine (ARM), focused both on the historic CRISPR approval and unmet need in SCD. “Today’s FDA approval of Casgevy for severe sickle cell disease marks a seminal moment in the history of biotechnology and human health,” he said. “The dual approvals for two distinct gene therapies for severe sickle cell disease are groundbreaking. A patient population that has been overlooked for far too long now has two durable, and potentially curative, treatment options."

“Today’s milestone will also pave the way for a coming wave of next-generation gene-editing treatments for a range of diseases, from other rare disorders to cancers,” Hunt added.

There are at least 120 clinical trials in gene editing globally, according to ARM, at least 90 of which use CRISPR, and 77% of these are targeting cancer indications.

Vertex and CRISPR expect an FDA decision for Casgevy in transfusion-dependent beta-thalassemia on or before March 30, 2024.

Heather McKenzie is a senior editor at BioSpace. You can reach her at heather.mckenzie@biospace.com. Follow her on LinkedIn.

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