Cell therapy weekly: Breyanzi CAR-T cell therapy secures new FDA approval
This week: The US Food and Drug Administration (FDA: MD, USA) accepted and granted a Priority Review of the Biologics License Application (BLA) for a gene therapy for aromatic L-amino acid decarboxylase deficiency (AADC) and approved a CAR-T therapy for relapsed or refractory follicular lymphoma (FL). Plus, Rocket Pharmaceuticals (NJ, USA) presented updated positive data from pivotal studies on investigational lentiviral gene therapies for rare blood conditions.
The news highlights:
- Gene therapy for AADC deficiency receives an FDA BLA acceptance
- Investigational lentiviral hematological portfolio for rare conditions receives positives data all round
- Breyzani CAR-T cell therapy secures new FDA approval
Gene therapy for AADC deficiency receives an FDA BLA acceptance
The FDA has accepted PTC Therapeutics’ (NJ, USA) BLA for Upstaza™ (eladocagene exuparvovec), a gene therapy for AADC deficiency, with a Priority Review and a target action date of 13 November 2024. Upstaza is designed to correct the genetic defect in AADC deficiency, a fatal disorder that commonly causes severe disability and suffering from the first few months of life with some instances of distressing seizure-like oculogyric crises and reduces life expectancy.
Upstaza is a one-time gene replacement therapy administered via a stereotactic surgical procedure, which is a minimally invasive neurosurgical procedure. The gene therapy is designed to correct the defective DDC gene by delivering a function copy directly into the putamen, increasing levels of the AADC enzyme and restoring dopamine production. Since the first patient was dosed in 2010, Upstaza has demonstrated efficacy and safety across clinical trials and compassionate use programs and improved neurological function.
“We are excited to be one step closer to bringing an approved therapy to patients with AADC deficiency in the United States,” said Matthew B. Klein, CEO of PTC Therapeutics. “The data collected to date continue to support the transformative benefit of Upstaza, this highly innovative gene therapy directly infused into the brain.”
Investigational lentiviral hematological portfolio for rare conditions receives positives data all round
Rocket Pharmaceuticals (NJ, USA) has reported long-term data updates from its hematology portfolio at the recent American Society of Gene and Cell Therapy annual meeting (ASGCT; 7-11 May 2024; Baltimore, USA). The portfolio consists of lentiviral-mediated gene therapies aimed at treating three rare conditions: Leukocyte Adhesion Deficiency (LAD-I), Fanconi Anemia (FA) and Pyruvate Kinase Deficiency (PKD).
LAD-I is a rare condition caused by a defect in the ITGB2 gene, which leads to a deficiency in CD18, disabling white blood cells from leaving the bloodstream to go to sites of infection or inflammation. Patients with severe LAD-I can develop life-threatening infections. In the Phase I/II trial of the investigational gene therapy KRESLADI™ (marnetegragene autotemcel), autologous hematopoietic stem cells were genetically modified with a lentiviral vector to deliver a functional copy of the ITGB2 gene. All primary and secondary endpoints were met.
Two-thirds of cases of FA, a rare genetic disorder affecting DNA repair, are caused by genetic defects in the FANCA gene, which may lead to the development of bone marrow failure, blood cancer or other cancers. In the Phase I/II study of the ex vivo lentiviral gene therapy RP-L102, data demonstrated that the gene could be a potentially curative therapy to prevent FA-related bone marrow failure. Participants showed sustained and progressively increasing genetic corrections of eight out of 12 of patients in the trial after a 12-month follow-up with no significant safety concerns.
The rare genetic blood disorder PKD is caused by a defect in the PKLR gene, limiting the ability of red blood cells to produce energy and remain intact, frequently resulting in anemia, chronic fatigue, yellowing of the skin and eyes and enlarged spleens. In the Phase I study of the investigational gene therapy RP-L301, autologous hematopoietic stem cells were genetically modified with a lentiviral vector containing a functional copy of the PKLR gene. Three out of four participants sustained improved hemoglobin normalization, there was no need for blood cell transfusion among all the patients and quality of life improved with no drug-related adverse events.
Breyanzi CAR-T cell therapy secures new FDA approval
The FDA has granted accelerated approval to Bristol Myers Squibb’s (NJ, USA) Breyanzi® (lisocabtagene maraleucel; liso-cel), a CD-19 CAR-T cell therapy, for adults with relapsed or refractory FL after at least two prior systemic therapies.
Breyanzi is administered as a one-time infusion with a single dose containing CAR-positive viable T cells that are produced from a patient’s own T cells that have been collected and genetically re-engineered into CAR-T cells. Breyanzi has demonstrated a consistent safety profile and is approved in the United States for relapsed or refractory large B-cell lymphoma (LBCL) after at least one prior therapy and is approved in Japan, the European Union and Switzerland for the second line of treatment for relapsed or refractory LBCL and in Japan, the European Union, Switzerland, the UK and Canada for relapsed or refractory LBCL after two or more lines of systemic therapy.
This approval is based on the therapy’s response rate and duration from the Phase II TRANSCEND FL study, which demonstrated a 95.7% overall response rate and a 73.4% complete response rate. The approval provides an option for patients with released or refractory FL with potentially lasting remission of one-time infusion for a historically considered incurable disease.
“In the treatment of relapsed or refractory follicular lymphoma, patients often cycle through treatments with typically shorter responses with each new line of therapy. Those who have experienced early disease progression have notably poor prognosis,” said the TRANSCEND investigator M. Lia Palomba.
