CD18

Last Friday, Rocket Pharma announced that the US health regulatory agency had not approved its investigational gene therapy for a rare and severe pediatric disease that significantly impacts the patients' immune system function. This news led to a significant over 12% drop in the company's stock price in early trading.   According to reports, the US Food and Drug Administration (FDA) responded with a detailed letter, requesting Rocket to provide limited additional information on certain processes for its gene therapy candidate named Kresladi, in order to complete a comprehensive review. Rocket is seeking the FDA's first approval for this therapy to treat severe Leukocyte Adhesion Deficiency-I (LAD-I) patients, with an estimated 800 to 1,000 patients affected in the US and Europe.   In these patients, a mutation in the protein encoded by the ITGB2 gene prevents white blood cells from properly adhering to the vessel walls at sites of infection, potentially leading to severe immune dysfunction and recurrent infections. Rocket stated that it has met with the FDA and discussed the required information to expedite the approval process.   The marketing authorization application is based on early to mid-stage clinical trial data, where all 9 patients treated survived at least 12 months post-treatment. However, in February this year, the FDA extended the review timeline for certain process data related to this gene therapy.   Analyst Tyler Van Buren from TD Cowen commented that this delay appears to be related to internal bandwidth issues at the FDA, rather than any issues with Rocket itself. He also noted that while Kresladi represents a relatively smaller market opportunity for Rocket, a successful approval would strongly validate the company's lentiviral platform, which is working to provide other treatment options for more patient populations.   Currently, the only treatment option for this disease is bone marrow transplantation, which is often difficult to obtain and carries significant risks.

Patients with leukocyte adhesion deficiency-I have white blood cells that cannot stick to the vascular endothelium and migrate to sites of infection. Image credit: Shutterstock / Anusorn Nakdee. The US Food and Drug Administration (FDA) has declined to approve Rocket Pharmaceutical’s Kresladi (marne-cel), requesting more information about the gene therapy’s manufacturing processes. The complete response letter (CRL) means Rocket’s therapy, indicated to treat severe leukocyte adhesion deficiency-I, has been delayed again in its path to approval. Shares in the US biotech dropped by 11% at market open on 28 June when the company announced the news, though they recovered by market close. Rocket had been anticipating a decision by the FDA by March 2024, but the agency pushed back the review period for Kresladi by three months to allow additional time to mull over supplemental chemistry, manufacturing, and controls (CMC) information. The FDA’s CRL has now asked Rocket for “limited additional” information related to CMC, as per a 28 June press release. See Also: Valneva’s chikungunya vaccine gains EC’s market authorisation UK’s antibiotic subscription funding model – a route to market sustainability? The delayed approval review also means Rocket will have to wait to receive a priority review voucher , given that Kresladi is being reviewed through the expedited rare paediatric designation programme. Once a therapy is approved through this pathway, the company receives a voucher. Rocket stated it has already met with the FDA to “align on the limited scope of additional CMC information needed to support the approval of Kresladi as quickly as possible.” Leukocyte adhesion deficiency-I is a rare genetic immune disorder that causes patients to be susceptible to recurrent infections. Those with the condition lack the protein-encoding ITGB2 gene, meaning white blood cells cannot stick to the vascular endothelium or travel to sites of infection. Certain complications from the disease can be life-threatening, with Rocket stating that without a successful bone marrow transplant, survival beyond childhood is rare. The exact incidence of leukocyte adhesion deficiency-I in the general population is unknown. Rocket reported a 100% overall survival in a global Phase I/II study at 12 months post-infusion of Kresladi. The trial met all primary and secondary endpoints with no treatment-related serious adverse events. Kresladi works by engineering haematopoietic stem cells taken from the patient with a genetically modified lentiviral vector (LV) to deliver a functional copy of the ITGB2 gene. Rocket is also awaiting an approval decision on its other gene therapy candidate RP-L102. The LV vector-based gene therapy is under review by the European Medicines Agency to treat the rare bone marrow disorder, Fanconi anaemia . Cell & Gene Therapy coverage on Pharmaceutical Technology is supported by Cytiva . Editorial content is independently produced and follows the highest standards of journalistic integrity. Topic sponsors are not involved in the creation of editorial content. Free Whitepaper Cell and gene therapies: Pipe dream to pipeline The cell and gene industry is gaining momentum, with a new wave of therapies promising to transform the way doctors treat, and even cure, disease. In this report, Cytiva and GlobalData have collaborated to explore the rise of the cell and gene therapy industries, the current state of the market, present and future opportunities for advancement, and the challenges that lie ahead. Thank you. You will receive an email shortly. Please check your inbox to download the Whitepaper. By Cytiva Thematic By downloading this case study, you acknowledge that GlobalData may share your information with Cytiva Thematic and that your personal data will be used as described in their Privacy Policy

Kresladi (marnetegragene autotemcel) originally had a PDUFA date of March 31 for LAD-I, a rare pediatric immunodeficiency disorder, but FDA made the call in February to push the review date to June 30 to allow additional time to review clarifying CMC information submitted by Rocket in response to the agency's information requests. LAD-1 is caused by mutations in the ITGB2 gene encoding for the beta-2 integrin component CD18, a key protein needed to combat infections. Rocket's Kresladi contains autologous hematopoietic stem cells that have been genetically modified with a lentiviral vector to deliver a functional copy of the ITGB2 gene, which encodes for the beta-2 integrin component CD18. The NJ-based biotech is hopeful that the therapy has the potential to change the treatment paradigm for patients living with severe LAD-I — one of the most aggressive and highly fatal immunodeficiencies ever characterized. Without a successful bone marrow transplant, mortality in patients with severe LAD-I is 60-75% prior to the age of 2 and survival beyond the age of 5 is uncommon, according to Rocket.