Gene Therapy Continues Edging into the Mainstream

Cell and Gene Therapy

Gene therapy is still very much cutting-edge, but companies are slowly making progress, with the potential to cure previously untreatable and incurable genetic diseases. Here’s some recent news in the space.

Sarepta’s DMD Gene Therapy Shows Robust Expression

Sarepta Therapeutics announced positive 12-week expression and safety data from the first 11 patients in its Study SRP-9001-103 ENDEAVOR study run in collaboration with Roche. SRP-9001 is an investigational gene transfer therapy designed to deliver its micro-dystrophin-encoding gene to muscle tissue for the treatment of Duchenne Muscular Dystrophy (DMD). The data showed robust expression of micro-dystrophin and no new safety signals.

“We are delighted by these seminal results from the ENDEAVOR Study, our first trial results with SRP-9001 made by our commercial-scale manufacturing process,” said Doug Ingram, president and chief executive officer of Sarepta. “These data show strong transduction of the micro-dystrophin gene, resulting in robust expression of the properly localized micro-dystrophin protein, and did so with no new or unexpected safety signals.”

Organicell’s Zofin for Severe COVID-19

Organicell Regenerative Medicine is presenting case reports at the International Society of Cell and Gene Therapy (ISCT) on its Zofin in three severely ill COVID-19 patients. The data showed that the drug is associated with decreased levels of inflammatory biomarkers, such as CRP and IL6. Zofin is an acellular biologic therapy originating from perinatal sources and manufactured to keep naturally occurring microRNAs. It contains over 300 growth factors, cytokines, and chemokines.

GenSight Biologics’ Therapy Restores Vision in Blind Patient

France’s GenSight Biologics published a case study of partial recovery of vision in a blind patient with late-stage retinitis pigmentosa (RP). The patient is part of the company’s ongoing PIONEER Phase I/II trial of GS030 optogenetic therapy. The research was published in Nature Medicine

RP is a leading cause of inherited blindness, caused by mutations in more than 71 different genes. GS030 uses the company’s optogenetics technology platform, delivering a gene encoding for a light-sensitive protein (ChrimsonR-tdT) into retinal ganglion cells, which makes them responsive to light and bypasses photoreceptors that were killed by the disease. A wearable medical device is needed to stimulate the treated retina.

“It was breathtaking to witness the first recovery of some visual function in a blind patient,” said Botond Roska, last and co-corresponding author and founding director of the Institute of Molecular and Clinical Ophthalmology Basel (IOB) in Switzerland, and co-founder of GenSight. “We have worked on optogenetic therapy in the lab for 16 years and now seeing the proof of concept in a patient is a unique experience.”

Ultragenyx’ Gene Therapy for Rare Liver Diseases Shows Durability

Ultragenyx Pharmaceutical announced positive longer-term data from the Glycogen Storage Disease Type Ia (GSDIa) and Ornithine Transcarbamylase (OTC) Deficiency Phase I/II trials. The data demonstrated ongoing durability of response in addition to advancements in the company’s HeLa producer cell line (PCL) manufacturing platform. 

There is some historical context that makes this remarkable. Twenty-one years ago, Jesse Gelsinger was treated with one of the first experimental gene therapies for OTC. Sadly, the case is considered a benchmark for conducting human trials, as that trial resulted in his death. 

Geisinger had a massive immune reaction to the modified adenovirus that was used as a vector. These viruses are used as vectors today but at much lower doses. This set back gene therapy for years.

Jesse’s father, Paul Gelsinger, not a scientist but who has followed the trial, told Science, “I think it’s great that Ultragenyx had the courage to take on OTC. … I also think it’s wonderful that they have achieved efficacy, even limited.”

Bluebird bio’s Skysona Receives Positive Opinion by CHMP in Europe

Bluebird bio’s Skysona (elivaldogene autotemcel, Lenti-D) received a positive opinion recommending marketing authorization by the European Medicines Agency (EMA)’s Committee for Medicinal Products for Human Use (CHMP). 

Skysona is a one-time gene therapy for early cerebral adrenoleukodystrophy (CALD) in patients less than 18 years of age with an ABCD1 genetic mutation and where HLA-matched sibling hematopoietic stem cell (HSC) donor is not available. If approved, it will be the first one-time gene therapy approved to treat CALD. 

CALD is a rare neurodegenerative disease that begins in childhood and can lead to progressive, irreversible neurological dysfunction and death.

“The goal of treatment with Skysona is to stabilize disease progression in children with CALD for whom a matched sibling donor is not available, in order to prevent further neurological decline and improve survival for these young patients,” said Richard Colvin, interim chief medical officer, bluebird bio. 

“This positive opinion from the CHMP marks the first regulatory approval recommendation for any gene therapy for CALD, bringing us closer to a one-time, durable treatment option that stabilizes neurological disease while reducing the risk of the serious immune complications associated with allogeneic stem cell transplantation (allo-HSCT), which is the only therapeutic option for children with this devastating disease.”


Back to news