New therapeutic development showing promise for infants with SMA
The early cancellation of the clinical trial for the experimental drug nusinersen found that the difference in the children given the drug, and those on the placebo was so drastic that doctors determined they could no longer administer the placebo in good conscience. The drug nusinersen is designed to help those affected by spinal muscular atrophy (SMA).
Dr. Craig Campbell is a scientist/paediatrician with the Children’s Hospital at London Health Sciences Centre who works closely with patients affected by SMA, and has seen first hand the encouraging signs the treatment has given some of his patients. We asked Dr. Campbell a few questions regarding the news of this clinical trial:
What is nusinersen and how does it work?
Nusinersen is an antisense oligonucleotide, which is basically a small piece of genetic material that works by tricking the cell machinery into reading and producing a normal SMN protein, from another gene that is very similar to the one missing in patients with SMA.
What improvements were seen in the clinical trial?
In both the infant and child study (SMA type 1 and 2 respectively) the motor skills were better than those treated with placebo. At this point we have not seen all the specific numbers, but for example in the SMA type 2 study the children actually improved over their baseline function by about 4 points on a motor scale we use to measure function in children with SMA. The placebo group declined by 2 points during the same 15 month time frame. It is very unusual for children with SMA to improve on this score as SMA is typically a disorder where patients decline in function over time.
How will the development of nusinersen continue now that the clinical trial showed a positive result?
All children on the trials have been moved over to open label extension studies, and the company has opened up a special access program so that all children with type 1 SMA can get access to nusinersen free of charge. Currently the investigative sites in Canada (Vancouver, London, Toronto, and Montréal) are taking referrals for SMA patients to get nusinersen. We anticipate that the company Biogen Inc. will be applying soon to Health Canada for a Notice of Compliance for a new drug.
Could a clinical trial for nusinersen open for adults affected by SMA?
I think it would be unlikely to happen any time soon. The company will probably apply for a wide label for the drug, and thus a trial for adults may not be needed. In the case that Health Canada limits the label to a specific age group, then a trial in adults may be needed.
What does this mean for research into other neuromuscular disorder treatments?
This has definitely helped give some enthusiasm and hope for the whole neuromuscular community, and it specifically gives some validity to the use of AON, which have been under trial in Duchenne MD (Eteplirsen and Drisapersen) and in Myotonic dystrophy (Ionis). However, it raises the question about how other medications can be tested in children with SMA now that an effective drug is on the market. Will placebo trials be possible, will there be enough children willing or able to participate in new trials, how will regulatory agencies respond to new trial applications? These are all not clear right now.
What are your hopes for the future use of this drug in patients with SMA?
We hope that we get Health Canada approval for a new drug in an accelerated manner, and that a thoughtful label is applied. Also we hope that a clear plan for coverage of the drug is established so that families do not have to pay or worry about access due to financial resources. Ideally this will be full government coverage, but other options will be important to explore such as managed access schemes.
Watch the CTV News feature video below, and read the accompanying article here.