A new drug for motor neurone disease has yielded “notable” results in a phase 3 trial, British researchers have reported.
Researchers from the University of Sheffield Institute for Translational Neuroscience (SITraN) and the Sheffield NIHR Biomedical Research Centre found the genetically targeted therapy tofersen slowed down progression of the disease, with patients reporting improved mobility and lung function after 12 months.
The phase 3 trial involved 108 MND patients with the faulty SOD1 gene.
Although there was no significant clinical improvement at the primary endpoint of the study at 28 weeks, when the trial was extended to 52 weeks the research team saw notable changes in patients’ motor function and lung function.
Results, published in the *New England Journal of Medicine*, show that six months after taking tofersen, there were biomarkers in patients’ spinal fluid that showed a reduction in the SOD1 and neurofilament protein levels.
This, says the team, suggests the treatment successfully hits the therapeutic target and reduces loss of motor neurones. However, it took longer for patients to experience reported physical improvements.
Professor Dame Pamela Shaw, professor of neurology and director of SITraN at the University of Sheffield, said: “I have conducted more than 25 MND clinical trials and the tofersen trial is the first trial in which patients have reported an improvement in their motor function. Never before have I heard patients say, ‘I am doing things today that I couldn’t do a few months ago – walking in the house without my sticks, walking up the garden steps, writing Christmas cards’. For me this is an important treatment milestone.”
She said while only about 2% of MND patients have SOD1 mutations, the results will change the future of MND trials for patients.
“Not only can we look at other genes which also cause MND, but we now have a biomarker which we can measure to see if a treatment is working,” she said.
“This is going to make trials much more efficient. In future we may be able to tell in three to six months if an experimental therapy is having a positive effect.”
Dr Brian Dickie, director of research at the MND Association said the trial results provide mounting confidence that tofersen is having both a biological and a beneficial clinical effect in people living with SOD1 MND.
“They also provide important ‘proof of concept’ that similar gene therapy-based approaches may be helpful for other forms of the disease” he said.
Clinicians and scientists hope that this is a first step towards a licensed therapy for MND patients.
Miller TM, Cudkowicz ME, Genge A et al. Phase 3 Trial of Antisense Oligonucleotide Tofersen for SOD1-ALS. *New England Journal of Medicine*. 21 September 2022
Leave a Reply