Gene Therapy Approvals Gain Steam in 2023: FDA Approves First Gene Therapies for Sickle Cell Disease

In a long-awaited milestone in the gene therapy space, the Food and Drug Administration (FDA) approved two gene therapies to cure sickle cell disease (SCD). Soon thereafter these approvals, a key licensing agreement was announced between Vertex and Editas for Cas9 gene editing technology.

Gene therapy is a new type of treatment with the potential to cure diseases by addressing the root cause of a disease rather than focusing on treating or reducing symptoms. In July 2023, we first posted about a series of FDA approvals in the first half of 2023 of several first-in-class gene- and cell-therapies for various rare inherited diseases. These therapies treatments for patients with dystrophic epidermolysis bullosa (DEB), Vyjuvek^TM, granted to Krystal Biotech, Inc; Duchenne Muscular Dystrophy (DMD), Elevidys^TM granted to Sarepta Therapeutics (“Sarepta”); adults with severe hemophilia A, Roctavian^TM, developed by BioMarin; and exagamglogene autotemcel (exa-cel), co-developed by Vertex Pharmaceuticals (“Vertex”) and CRISPR Therapeutics.

In November 2023, we posted a second article about therapies that cleared regulatory milestones in the second half of 2023. These milestones included the approval of an Investigational New Drug (IND) application for NTLA-2001, developed by Intellia Therapeutics, Inc. (“Intellia”) in collaboration with Regeneron Pharmaceuticals (“Regeneron”) for the treatment of transthyretin (ATTR) amyloidosis with cardiomyopathy; the Priority Medicines (PRIME) Designation granted by the European Medicines Agency (EMA) to Intellia for NTLA-2002 for the treatment of hereditary angioedema (HAE); an assessment provided by an advisory committee to the FDA regarding exa-cel for the treatment of SCD; the Regenerative Medicine Advanced Therapy (RMAT) designation granted to Editas Medicine, Inc.’s (“Editas”) EDIT-301 for treatment of SCD and beta thalassemia; Sarepta’s announcement of its phase 3 study results for ELEVIDYS for treatment of Duchenne Muscular Dystrophy (DMD); and FDA’s approval of the BioMarin Pharmaceutical Inc.’s (“Biomarin”) supplemental New Drug Application (sNDA) for VOXZOGO® (vosoritide) to expand its indication for children with achondroplasia.

In this post, we provide updates on recent approvals for SCD.

On December 08, 2023, the FDA approved two gene therapy treatments, Casgevy^TM and Lyfgenia^TM, for the treatment of SCD in patients 12 years and older. Casgevy^TM is listed at $2.2 million for the one-time therapy while Lyfgenia^TM is priced at $3.1 million.

SCD is an inherited blood disorder that affects approximately 100,000 people in the U.S. SCD is caused by a mutation in the oxygen-carrying protein hemoglobin found in red blood cells (RBC). The SCD mutation causes hemoglobin to be misshapen and become stuck in blood vessels, leading to organ damage. Until now, the only cure for some SCD patients has been a bone marrow transplant, which carries the risk of rejection by the recipient’s immune system. Additionally, it can be difficult to find suitable donors for patients.

Casgevy^TM (exa-cel), was developed by Vertex Pharmaceuticals and CRISPR Therapeutics. Casgevy^TM is a first-in-class treatment, which uses the Nobel Prize winning CRISPR/Cas9 genome-editing system to edit the patient’s own autologous CD34+ hematopoietic stem cells (HSCs) ex vivo and then introducing the edited cells back into the patient’s body. We have discussed regulatory milestones for this therapy in the previous articles in this series. Casgevy^TM is also conditionally granted marketing authorization in the United Kingdom and Bahrain for patients 12 years of age and older for whom stem cell transplantation is appropriate. Casgevy^TM is also pending review with the European Medicines Agency (EMA) and the Saudi Food and Drug Agency.

Lyfgenia^TM was developed by Bluebird Bio (“Bluebird”). Like Casgevy^TM, Lyfgenia^TM is indicated as a one time treatment for patients 12 years or older with SCD. While it is also an ex vivo therapy, Lyfgenia^TM edits the genome of the patient’s own HSCs using a lentiviral vector as opposed to CRISPR/Cas9. This approval marks Bluebird’s third FDA approved ex vivo gene therapy using its lentiviral gene editing system. Bluebird explained that it set the $3.1 million cost for Lyfgenia^TM “in recognition of the value the therapy may deliver through robust and sustained clinical benefits and the estimated lifetime impact that reducing or eliminating VOEs may have on patients’ healthcare utilization, future earnings, and life opportunities.”

Soon after these approvals, on December 11, 2023, Editas announced new safety and efficacy data in 17 patients treated with its gene editing medicine, EDIT-301, now known as renizgamglogene autogedtemcel (reni-cel), in the RUBY trial for SCD (n=11) and in the EdiTHAL trial for transfusion-dependent beta thalassemia (TDT) (n=6) in a single-arm, open-label, multi-center Phase 1/2 study designed to assess the safety and efficacy of reni-cel in patients with severe sickle cell disease. All RUBY patients with ≥5 months follow-up have achieved a normal hemoglobin level and a fetal hemoglobin level of >40% and EDIT-301 was well-tolerated and demonstrated a safety profile consistent with myeloablative conditioning with busulfan and autologous hematopoietic stem cell transplant.

And on December 13, 2023, Editas announced that it entered into a non-exclusive licensing agreement with Vertex for Editas’s Cas9 gene editing technology for ex vivo gene editing medicines targeting the BCL11A gene in the fields of sickle cell disease and beta thalassemia. CRISPR-Cas technology has been the subject of a series of lawsuits both at the Patent and Trademark Office (PTAB) and in U.S. Federal Courts between UC Berkeley and the Broad Institute. The Broad Institute, which was the winner of those patent disputes in the U.S., exclusively licenses certain CRISPR patents for making human medicines to Editas. As part of this licensing agreement, Vertex will pay Editas $50 million upfront along with a series of annual payments ranging from $10 million to $40 million annually through 2034. Editas, in turn, will pay the Broad Institute and Harvard a mid-double digit percentage of payments received from Vertex.

These breakthrough gene therapies close out a triumphant 2023 for the gene editing field and lead into an exciting 2024 with more gene editing products in the pipeline. Given the relatively large number of SCD patients compared to the rare disease indications of previously approved gene therapies, as well as the increasing number of competing manufacturers, the market is set to hit an inflection point as is the landscape for patent licensing and litigation activity.

We will continue to monitor updates in this exciting area and provide updates as they become available.