An experimental drug for motor neurone disease (MND) has shown signs of slowing the progress of the devastating illness in a landmark trial.
The results provide fresh hope after a phase-three trial of the same drug had previously failed to make a meaningful difference to patient outcomes after six months of treatment.
The latest results suggest that when patients continued taking the Biogen drug, Tofersen, for another six months they experienced better mobility and lung function, with some reporting remarkable outcomes.
One man, who was in a wheelchair when he enrolled on the trial, was able to walk without a stick again and another patient described being able to write their own Christmas cards again after receiving the gene-targeted treatment.
Dame Pamela Shaw, professor of neurology at the University of Sheffield and a co-author of the study, said: “I believe this is really significant. I’ve done more than 25 trials and never before have I heard patients report stabilisation or improvement.”
The drug works by targeting a genetic mutation, SOD1, which is the known cause for 2% of MND patients, but experts said the groundbreaking results could pave the way for a new class of gene-targeted treatments for a far wider cohort of patients.
Les Wood, 68, from Thorne, South Yorkshire, was diagnosed with MND 10 years ago and was one of the first to be enrolled on the trial in 2016. After the first 12 months of taking Tofersen, Wood was well enough to return to enjoying holidays in Spain with his wife, Val.
“I could actually walk in the house without sticks, I was able to come off some of my painkillers and I felt a lot better in myself,” he said. “MND is a progressive disease so, although my symptoms have continued to worsen, I would not be without the drug and the difference I know it has made to my quality of life.”
MND, also known as amyotrophic lateral sclerosis, affects 5,000 people in the UK and, until now, the outlook has been bleak. The fatal disease progressively destroys nerve cells in the brain and spinal cord, cutting communication with muscles that then begin to weaken, stiffen and waste.
Few survive beyond five years and current treatments only marginally increase life expectancy and do not delay the loss in the patient’s ability to walk, talk, eat and breathe.
In the initial phase, 108 MND patients with SOD1 mutations were recruited and two-thirds were given monthly doses of the drug via lumbar puncture, with the rest receiving a placebo.
Tofersen is a so-called antisense oligonucleotide, a DNA-based drug that works by blocking the production of a toxic version of the SOD1 protein that is caused by the genetic defect.
After six months, the drug had significantly lowered levels of the faulty protein, but there was not a clinically significant difference in the patient’s mobility or lung function. However, the results were encouraging enough that the trial was extended, with those who had been on a placebo treatment switching over to the drug at that point.
Six months into the extension, a significant difference in motor and lung function between the early and late starters on the drug was revealed, according to results published in the New England Journal of Medicine. The researchers believe the lag simply reflects the length of time it takes for motor neurons to heal and for the drug to make a clinical difference.
The drug is not viewed as a cure – although it might have a more powerful effect if given earlier in the course of disease – but even delaying the progress of MND is viewed as a major advance.
The FDA is considering an application to license the drug and it is being offered to patients in the UK under an early access programme.
“The thing that makes MND so scary is the speed of change,” said Shaw. “Often patients can’t get their head around one aspect of disability before something new has to be faced. If we can slow it down, it makes it much more livable, much less scary.”
Dr Brian Dickie, director of research at the MND Association, said: “These latest 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.”