Cell therapy weekly: in vivo CAR-T technology acquisition
This week: Regeneron Pharmaceuticals (NY, USA) reported positive updated data from its pivotal CHORD trial for DB-OTO gene therapy for genetic deafness, Rocket Pharmaceuticals (NJ, USA) received FDA acceptance of its resubmitted Biologics License Application for KRESLADI™ gene therapy targeting severe Leukocyte Adhesion Deficiency-I, and Bristol Myers Squibb (NY, USA) announced a US$1.5 billion acquisition of Orbital Therapeutics (MA, USA) to gain access to its RNA-based in vivo CAR-T technology for autoimmune diseases.
The news highlights:
- Update on gene therapy trial for genetic deafness
- Biologics License Application for lentiviral vector-based gene therapy approved
- Bristol Myers Squibb will acquire Orbital Therapeutics for US$1.5 billion
Update on gene therapy trial for genetic deafness
Regeneron Pharmaceuticals has provided updated data from the pivotal CHORD trial assessing their investigational gene therapy DB-OTO. DB-OTO is intended to treat profound congenital hearing loss due to variants of the otoferlin (OTOF) gene. Through a single administration, via a surgical procedure, this investigational gene therapy aims to provide durable physiological hearing to individuals by delivering a working copy of the OTOF gene to replace the non-functional otoferlin protein.
“Until now, genetic OTOF-related hearing loss was considered permanent, which is why many of us have dedicated our careers to this field,” said Lawrence Lustig, Chair of the Department of Otolaryngology-Head and Neck Surgery at the Columbia University College of Physicians and Surgeons (NY, USA).
The latest results from the trial, which included participants aged 0 months to 16 years, showed that:
- 9 participants achieved ≤70 dB hearing levels, a clinical standard that typically does not require cochlear implantation and enables natural acoustic hearing
- 9 participants demonstrated auditory brainstem response at ≤90 decibels, meeting the trial’s key secondary endpoint
- Within weeks of treatment, 11 of 12 participants experienced clinically meaningful hearing improvements, including three who achieved normal hearing levels
- 8 participants with longer follow-up periods showed stability or continued improvement in their hearing over time
- One participant who did not meet the primary behavioral pure tone audiometry endpoint at week 24 continued to improve and achieved “nearly normal” hearing sensitivity by week 48
- 6 participants could hear soft speech without assistive devices, and three were able to detect whispers, achieving normal hearing sensitivity
- All 3 individuals who completed speech assessments demonstrated significant improvement in their speech abilities
“This registrational data set showcases consistent, rapid and robust responses to DB-OTO, and for those followed to later timepoints, we’ve seen hearing stability as well as continued improvement in understanding of speech. These results are even more poignant when viewed by the families – as one of the parents said, their situation is now ‘unimaginable’ from one year ago,” said Lustig. “This truly represents a new era in the treatment of hearing loss.”
Biologics License Application for lentiviral vector-based gene therapy approved
Rocket Pharmaceuticals has announced that the FDA has accepted the resubmitted Biologics License Application for KRESLADI™ (marnetegragene autotemcel). This investigational lentiviral vector-based gene therapy targets severe Leukocyte Adhesion Deficiency-I (LAD-I), a rare genetic immune disorder causing recurrent, life-threatening infections that is typically fatal in childhood without stem cell transplantation. The FDA has set a Prescription Drug User Fee Act review completion date of March 28, 2026.
“Bone marrow transplant is currently the only treatment option, has substantial morbidity, mortality, and cost, and may not be available in time for these children,” said Gaurav Shah, CEO, Rocket Pharma. “As we approach our new PDUFA date, we are focused on the opportunity to make this therapy available to patients who need it most.”
Bristol Myers Squibb will acquire Orbital Therapeutics for US$1.5 billion
Bristol Myers Squibb (BMS) and Orbital Therapeutics have announced a definitive agreement under which BMS will acquire Orbital for US$1.5 billion.
Orbital is a biotechnology company developing novel RNA-based therapeutics that enable immune cell reprogramming in vivo. The company’s lead candidate, OTX-201, delivers genetic instructions via targeted nanoparticles that reprogram immune cells directly inside the patient to target and eliminate autoreactive B cells responsible for autoimmune diseases.
“In vivo CAR T represents a novel treatment approach that could redefine how we treat autoimmune diseases,” said Robert Plenge, executive vice president, Chief Research Officer, BMS. “This acquisition enhances our robust cell therapy research platform and provides an opportunity to advance a potential best-in-class therapy designed to deplete autoreactive B cells and reset the immune system. We are excited by the promise this holds for patients with autoimmune diseases who are waiting for better options.”