Announcement • Mar 28
Rocket Pharmaceuticals Announces FDA Approval of KRESLADI™ for Pediatric Patients with Severe Leukocyte Adhesion Deficiency-I (LAD-I)
Rocket Pharmaceuticals, Inc. announced that the U.S. Food and Drug Administration (FDA) has granted accelerated approval for KRESLADI (marnetegragene autotemcel), an autologous hematopoietic stem cell-based gene therapy indicated for the treatment of pediatric patients with severe leukocyte adhesion deficiency-I (LAD-I) due to biallelic variants in ITGB2 without an available human leukocyte antigen-matched sibling donor for allogeneic hematopoietic stem cell transplant. This indication is approved under accelerated approval based on increase in neutrophil CD18 and CD11a surface expression. Confirmation of clinical benefit will be based on the evaluation of longer-term follow-up data of treated patients in the ongoing clinical study and through a post-marketing registry. With the approval of KRESLADI, the FDA granted Rocket a Rare Pediatric Disease Priority Review Voucher (PRV), a program designed to encourage development of therapies for rare pediatric diseases. LAD-I is an ultra-rare genetic pediatric disease caused by mutations in the ITGB2 gene encoding for CD18, a key protein that is expressed along CD11 integrins to facilitate leukocyte adhesion to the blood vessel wall and migration to tissues to confine and clear infections and orchestrate wound repair. Patients with severe LAD-I typically show very diminished CD11a expression. Infants with severe LAD-I suffer from recurrent, life-threatening bacterial, and fungal infections that respond poorly to antimicrobials and require frequent hospitalizations. In the U.S., the incidence of LAD-I is estimated to range from approximately one in 100,000 to one in 200,000 live births, with roughly two-thirds of affected patients classified as having the severe form of the disease. More information is available for patients, families, and healthcare providers in the U.S. at www.KRESLADI.com, including full Prescribing Information. Research supporting the development of KRESLADI was made possible in part by funding from the California Institute for Regenerative Medicine (Grant Number CLIN2-11480). KRESLADI is an autologous hematopoietic stem cell-based gene therapy indicated for the treatment of pediatric patients with severe leukocyte adhesion deficiency-I (LAD-I) due to biallelic variants in ITGB2 without an available human leukocyte antigen (HLA)-matched sibling donor for allogeneic hematopoietic stem cell transplant. This indication is approved under accelerated approval based on increase in neutrophil CD18 and CD11a surface expression. Continued approval may be contingent upon verification and description of clinical benefit in a confirmatory trial(s). Serious infections have occurred with KRESLADI administration. Increased susceptibility to infections may occur due to administration of myeloablative conditioning prior to KRESLADI infusion. Anti-retroviral medications may interfere with manufacturing of KRESLADI. If a patient requires anti-retrovirals for HIV prophylaxis, mobilization and apheresis of CD34+ cells for KRESLADI manufacturing should be delayed until HIV infection is adequately ruled out. Patients should not take anti-retroviral medications for at least one month prior to mobilization, or for the expected duration required for the elimination of the anti-retroviral medications, and until all cycles of apheresis are completed. Patients who have received KRESLADI are likely to test positive by polymerase chain reaction (PCR) assays for HIV due to LVV provirus insertion resulting in a false-positive test for HIV. Therefore, patients who have received KRESLADI should not be screened for HIV infection using a PCR-based assay. Patients treated with KRESLADI should not donate blood, organs, tissues, or cells for transplantation at any time in the future. The most common non-laboratory adverse reactions (= 30% of patients) include: mucositis, upper respiratory tract infection, viral infection, febrile neutropenia, skin lesion, nausea/vomiting, rash/dermatitis, pyrexia, device related infection, and skin infection. The most common laboratory adverse reactions (= 30% of patients) include: hemoglobin decreased, platelet count decreased, neutrophil count decreased, leukocyte count decreased, aspartate aminotransferase increased, and alanine aminotransferase increased. For additional safety information, refer to the full Prescribing Information. No formal drug interaction studies have been performed. KRESLADI is not expected to interact with the hepatic cytochrome P-450 family of enzymes or drug transporters. The safety and effectiveness of immunization with live viral vaccines during or following KRESLADI treatment has not been studied. Vaccination is not recommended during the 6 weeks preceding the start of myeloablative conditioning, and until hematological recovery following treatment with KRESLADI. Where feasible, administer childhood vaccinations prior to myeloablative conditioning for KRESLADI. Patients should not take anti-retroviral medications for at least one month prior to initiating medications for stem cell mobilization and for the expected duration for elimination of the medications, and until all cycles of apheresis are completed. Anti-retroviral medications may interfere with manufacturing of KRESLADI. Please see full Prescribing Information for KRESLADI.
