Orchard Therapeutics’ gene therapy for metachromatic leukodystrophy (MLD) resulted in motor ability improvements more than six times over the target endpoint, according to data released at a recent symposium.
“Metachromatic leukodystrophy is a rare disease that affects the brain,” explained Mark Rothera, CEO of Orchard Therapeutics. “Kids born with MLD lose motor function very fast and they also lose cognitive function. In the fastest progressing form, life expectancy is about five or six years.”
Currently, there are no effective treatments for MLD. Orchard is developing a gene therapy that aims to put an end to that.
The treatment provides a functional copy of the DNA that encodes for the ARSA enzyme. This enzyme, which is mutated in children with the condition, is responsible for clearing up sulfatide molecules to prevent them from accumulating in nerves and impairing their function.
During a symposium organized by the Society for the Study of Inborn Errors of Metabolism in the Netherlands, Orchard presented data proving that its therapy has potential to reverse MLD and give children with the condition a chance to lead a normal life. The company saw a significant improvement, six times over the initial target, in the motor ability of patients treated with a single dose of the therapy. There were no side effects or deaths due to the treatment.
The data comes from 20 patients in a clinical trial performed at the San Raffaele-Telethon Institute for Gene Therapy in Milan, Italy, together with 9 patients that were treated in compassionate use cases. Of them, 26 are still alive. Some were treated almost 8 years ago now.
“Instead of launching a chronic treatment, which, by the way, nobody has been able to do, we’re developing a one-off intervention that has the potential to give a child born with this condition a normal life span and a normal life,” remarked Rothera.
Orchard Therapeutics is aiming to file for approval of the therapy in Europe in the first half of 2020, and in the US one year later.
Gene therapy has sparked controversy recently over its pricing — with examples such as Novartis’ Zolgensma and bluebird bio’s Zynteglo, which both carry a price tag of over €1M. The investment firm Goldman Sachs controversially stated that curing patients is not a sustainable business model, but Rothera disagrees.
“You’re collapsing a lifetime of value into one single intervention,” he said. “I think it is intrinsically a very valuable proposition for the healthcare system, for patients, and for society. We’re highly engaged in conversations with peers and people involved in the system to build a sustainable business that can work for the healthcare system.”
Orchard Therapeutics also presented data on a gene therapy intended to treat another neurometabolic syndrome called mucopolysaccharidosis type I (MPS-I). The company reported that the two patients treated so far have experienced a correction of the symptoms of the disease.