CGTLive's Pillars of Progress 2023: Top FDA Approval News in Cell and Gene Therapy

The efforts of the CGTLive^™ team in 2023 included advances in the clinical development of targeted and novel engineered approaches to various diseases, including each step of progress that the most exciting cellular and genetic treatments have made along the pipeline, and most notably, their FDA decisions.

Always among our areas of focus is the FDA approval of new medicines—something that occurred several times in 2023. These major news items appeared among the top pieces our team produced, and whatever the reason for the attention these stories got, their place here helps provide an understanding of the themes in cell and gene medicine over the year.

As part of a larger look back at the FDA’s decisions in 2023, our sister publication HCPLive^® sat down with Robert M. Califf, MD, MACC, the commissioner of food and drugs at the FDA, to discuss the progress made in gene therapy and cell therapy this year. Califf spoke about the importance of past research efforts, especially the Human Genome Project, in bringing the field to where it is today, and expressed optimism for the future, but pointed out the need to continue to pay close attention to safety and to work with the Centers for Medicare & Medicaid Services regarding economic affordability for these emerging treatment modalities.

Check out Califf's insight in the video below.

Now, we'll highlight some of those approvals this year by sharing with you the most-read FDA approval stories that ran on CGTLive this year. Click the buttons to read further into these stories.

FDA Approves Omidubicel to Reduce Infection Risk in Patients With Hematologic Malignancies Undergoing Stem Cell Transplant

• Omidubicel is a single intravenous infusion of patient-specific human allogeneic cord blood-derived stem cells processed and cultured with nicotinomide.
• Omidubicel showed faster neutrophil recovery compared to other donor sources.
• Despite higher rates of acute graft-versus-host disease, the therapy demonstrated comparable overall and disease-free survival rates at the median follow-up of 22 months.

April 17, 2023 — The FDA approved Gamida Cell's allogeneic cell therapy, omidubicel, to reduce the risk of infection in patients aged 12 years and older undergoing stem cell transplantation for hematologic cancer. The approval marks a significant step forward in the cell therapy space as researchers continue to identify unmet treatment needs. Omidubicel, which will be marketed as Omisirge, is delivered as a single intravenous infusion composed of patient-specific human allogeneic cord blood-derived stem cells that have been processed and cultured with nicotinomide, a form of vitamin B3.

“Today’s approval is an important advance in cell therapy treatment in patients with blood cancers. Hastening the return of the body’s white blood cells can reduce the possibility of serious or overwhelming infection associated with stem cell transplantation. This approval reflects the FDA’s continued commitment to supporting development of innovative therapies for life-threatening cancers."

– Peter Marks, MD, PhD, of FDA

B-VEC Gene Therapy Approved for Dystrophic Epidermolysis Bullosa

• This marks the first-ever gene therapy approved for this indication, and it will be marketed under the name Vyjuvek.
• The therapy delivers COL7A1 to restore the C7 protein, which is essential for skin stabilization. B-VEC is administered topically in a gel droplet form to wounds weekly.
• The approval is based on data from the phase 2 GEM-1/2 study and the phase 3 GEM-3 study, showing that B-VEC is safe and effective.

May 19, 2023 — The FDA approved beremagene geperpavec (B-VEC), a topical and redosable gene therapy from Krystal Biotech, for the treatment of dystrophic epidermolysis bullosa (DEB) in patients 6 months or older. The gene therapy, the first for this indication, will be marketed under the name Vyjuvek. B-VEC’s biologics license application (BLA) was supported by data from 2 intrapatient, placebo-controlled clinical trials: the phase 2 GEM-1/2 (NCT03536143) study and the phase 3 GEM-3 study (NCT04491604).

"For so many years, all we have been able to offer DEB patients was palliative care, but now, based on the strength of the Company’s clinical trial data, there is a safe and effective FDA-approved treatment."

– Suma Krishnan, of FDA

FDA Approves Sarepta's Landmark DMD Gene Therapy Elevidys

• The gene therapy is approved for treating ambulatory pediatric patients aged 4 through 5 years with DMD and a confirmed mutation in the DMD gene, excluding patients with any deletion in exon 8 and/or exon 9.
• It is the first and only gene therapy approved for Duchenne, and its approval is expected to make a meaningful difference in the lives of young patients with this progressive and debilitating condition.
• No serious adverse events were reported, and patients demonstrated improvements contrary to the typical decline expected in this age range for patients with DMD.

June 22, 2023 — The FDA approved Sarepta Therapeutics’ delandistrogene moxeparvovec (SRP-9001) for treating ambulatory pediatric patients aged 4 through 5 years with Duchenne muscular dystrophy (DMD) and a confirmed mutation in the DMD gene, excluding patients with any deletion in exon 8 and/or exon 9, to be marketed under the name Elevidys. The FDA previously pushed back the action date for the therapy from May 29 to June 22, 2023, possibly partially because of recent discussions on microdystrophin, which may have also prompted the FDA to hold a FDA Cellular, Tissue, and Gene Therapies Advisory Committee meeting for the therapy after previously stating one would not be needed. Although split, the committee eventually voted 8–6 (8 Yes; 6 No; 0 Abstain) in support of the therapy’s approval to the question of whether or not definitive clinical benefit could be observed with microdystrophin expression as a surrogate end point.

"It is gratifying and a relief to finally have an approved gene therapy for DMD. This drug is likely to be the most potent treatment method available today, although it is not as robust as many had hoped. Nonetheless, approval sets the stage for intensive analysis of the long-term effects of this gene therapy, and will hopefully spur increased research and testing of improved next generation gene therapies."

– Jeffrey Chamberlain MD, PhD, of University of Washington St. Louis

FDA Approves Lantidra Cell Therapy for Type 1 Diabetes

• Lantidra is the first cell therapy approved for patients with type 1 diabetes.
• The FDA's approval is based on safety and efficacy data from 2 open-label, single-arm studies involving 30 participants.
• Common adverse events included nausea, fatigue, anemia, diarrhea, and abdominal pain. Most participants experienced at least 1 serious adverse event related to infusion or immunosuppression.

June 28, 2023 — The agency approved CellTrans’ donislecel allogeneic pancreatic islet cell therapy, under the name Lantidra, for treating adults with type 1 diabetes who are unable to approach target glycated hemoglobin because of current repeated episodes of severe hypoglycemia despite intensive diabetes management and education. The decision was based on safety and efficacy data from 30 participants in 2 open-label, single-arm studies (NCT03791567; NCT00679042) that received 1 to 3 infusions of donislecel.

"Severe hypoglycemia is a dangerous condition that can lead to injuries resulting from loss of consciousness or seizures. Today’s approval, the first-ever cell therapy to treat patients with type 1 diabetes, provides individuals living with type 1 diabetes and recurrent severe hypoglycemia an additional treatment option to help achieve target blood glucose levels."

– Peter Marks, MD, PhD, of the FDA

FDA Approves BioMarin’s Hemophilia A Gene Therapy Roctavian

• Roctavian is the first gene therapy approved in the United States for the treatment of adults with severe hemophilia A.
• A 3-year data analysis showed a mean reduction of 52% in annualized bleeding rate and improvements in other functional measures, with 92% of participants not resuming prophylaxis at the 3-year timepoint.
• BioMarin has introduced an outcomes-based warranty for Roctavian to US insurance companies. This warranty includes a provision for full reimbursement if a patient's disease does not respond to treatment.

June 29, 2023 — The FDA approved BioMarin’s valoctocogene roxaparvovec (val-rox) for the treatment of adults with severe hemophilia A defined as congenital factor VIII deficiency with FVIII activity of less than 1 IU/dL who do not have antibodies to adeno-associated virus serotype 5 (AAV5) according to an FDA-approved test. Val-rox will be marketed in the United States under the name Roctavian; it is the first gene therapy for hemophilia A to be approved in the US. The decision was based on data from the phase 3 GENEr8-1 clinical trial (NCT03370913) Val-rox is contraindicated for patients with acute or uncontrolled chronic infections, significant hepatic fibrosis, cirrhosis, or hypersensitivity to mannitol.

"The approval of Roctavian, as the first gene therapy for severe hemophilia A, has the potential to transform the way we treat adults based on years of bleed control following a single, 1-time infusion."

– Steven Pipe, MD, of CS Mott's Children's Hospital

FDA Approves bluebird bio's Lovo-Cel Gene Therapy for Sickle Cell Disease

• This gene therapy involves autologous CD34+ hematopoietic stem cells transduced with BB305 lentiviral vector encoding the human beta-A-T87Q globin gene.
• Serious adverse events related to lovo-cel included cases of anemia in 2 patients with alpha-thalassemia and leukemia (not resulting from insertional oncogenesis) in 2 patients.
• Hematologic malignancy has occurred in patients treated with lovo-cel, leading to a black box warning on the therapy's label, emphasizing the need for lifelong monitoring for these malignancies.

December 8, 2023 — The FDA approved bluebird bio’s lovotibeglogene autotemcel (lovo-cel), marketed as Lyfgenia, as a treatment for sickle cell disease (SCD) in patients aged 12 years and older. The therapy consists of autologous CD34+ hematopoietic stem cells collected by plerixafor mobilization and apheresis, transduced with BB305 lentiviral vector (LVV) encoding the human beta-A-T87Q globin gene. The company’s biologics license application was supported by efficacy data from 36 patients from the ongoing phase 1/2 HGB-206 clinical trial (NCT02140554) and 2 patients in the phase 3 HGB-210 clinical trial (NCT04293185).

"I do support [lovo-cel's] approval. I think it's going to be very complicated, because we need to support sickle cell disease centers in delivering this product, as well as the product itself, which are sort of 2 different price streams. And I think it'll be a little bit complicated as we wander into this new territory of high-priced therapies. But I think the patients that I have taken care of would tell you it is absolutely worth it. It is truly a transformative therapy."

– Julie Kantor, MD, of University of Alabama at Birmingham

FDA Approves Exa-cel, Vertex and CRISPR Therapeutics’ Gene Therapy, for Sickle Cell Disease

• This groundbreaking approval marks the first instance of a CRISPR-based gene therapy being approved in the United States.
• The dual approvals represent a pivotal moment in biotechnology and human health, offering durable and potentially curative treatment options for a population historically overlooked.
• The FDA's decision for exa-cel was based on results from the phase 1/2/3 CLIMB-121 clinical trial (NCT03745287) conducted exclusively in patients with SCD.

December 8, 2023 — The FDA has approved Vertex Pharmaceuticals' and CRISPR Therapeutics’ autologous gene-edited cell therapy exagamglogene autotemcel (exa-cel), marketed under the name Casgevy, for the treatment of severe sickle cell disease (SCD) in patients aged 12 years and older with recurrent vaso-occlusive crises. The FDA’s decision was based on results from the phase 1/2/3 CLIMB-121 clinical trial (NCT03745287), which was conducted exclusively in patients with SCD, and the phase 3 long-term follow-up study CLIMB-131 (NCT04208529), which includes both patients with SCD and patients with transfusion-dependent β-thalassemia.

"Today’s FDA approval of Casgevy for severe SCD marks a seminal moment in the history of biotechnology and human health. As the first gene-editing medicine approved in the US, Casgevy represents a durable and potentially curative treatment option for a population that has been overlooked for far too long—and one that is the largest to date for a gene therapy. Importantly, 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."

– Tim Hunt, JD, of Alliance for Regenerative Medicine