This is the second time the FDA has delayed the approval process of marnetegragene autotemcel or ‘Kresladi’ since the New Jersey-based biotech submitted the lentiviral vector-based gene therapy for priority review by the regulator in Oct 2023.
The company was hoping to receive a decision from the FDA in March this year, but a delay of 3 months was issued until the end of June so that Chemistry, Manufacturing, and Controls (CMC) information could be clarified.
After this review, Rocket announced in a recent press statement that the FDA have now requested “limited additional CMC information to complete its review.”
Representatives from the company met with FDA staff from the Center for Biologics Evaluation and Research (CBER) to find out more information on the extra information that is being requested, to try and expedite the approval process.
“It is reassuring to have the FDA as a close collaborator who understands the high unmet medical need, clear clinical benefit and importance of timely patient access,” said Gaurav Shah, CEO of Rocket Pharma in the most recent statement from the company.
“CBER leadership’s direct involvement and commitment to working expeditiously to deliver this therapy to patients gives us great hope on behalf of the primary immunodeficiency community.”
Rocket shares have fallen by around 14% in the last 5 days in response to the statement.
Important milestone for Rocket platform
Rocket specializes in developing gene therapies using lentiviral vectors for rare conditions such as severe Leukocyte Adhesion Deficiency-I (LAD-I). This is a rare genetic condition impacting the immune system, estimated to affect up to 1000 people in Europe and the US.
Getting approval is important for the company, as although it has several therapy candidates in development, none have yet been approved. Kresladi shares lead candidate status with RP-L102, another lentiviral vector therapy that is designed to treat Fanconi anemia. RP-L102 has been submitted to the European Medicines Agency for review, but the company has not yet announced a submission to the FDA.
Due to the rarity of the condition, Kresladi is eligible for priority review by the FDA, which should speed up the review process significantly compared to that of therapies not eligible for fast-track status. If the therapy gets approved, the company will be eligible to claim a priority review voucher from the agency as a reward. These vouchers can then be used to speed up review of another drug candidate from the company in the future or be sold to another company to recoup funds.
Putting the patients first
LAD-I is inherited in an autosomal recessive manner and caused by mutations in a gene called ITGB2. This gene encodes a protein called CD18, which plays an important role in fighting infections and this ability is impacted by the genetic variants inherited by those with LAD-I. Children with the condition are vulnerable to serious, potentially life-threatening infections, often from shortly after birth.
The only real option for these children at present is to have a bone marrow transplant. Although this can help these children to survive, it is an intensive and difficult process and is not always available for those who need it. For this reason, there is an unmet need for new therapies for those affected.
Kresladi is a gene therapy comprised of patient derived hematopoietic stem cells modified with a lentiviral vector to contain a functional copy of the ITGB2 gene. A phase 1/2 trial of Kresladi in patients with the condition demonstrated 100% survival 12 months after an infusion of the therapy. Nine patients had 18-42 months of follow up data and survival was also 100% in this group for the whole follow up period.
Infection rate was also much lower in patients with LAD-I after the infusion compared with earlier rates of infections for this group.