DocWire News recently sat down with Shephard Mpofu, M.D., SVP, Chief Medical Officer, Novartis Gene Therapies, to discuss important data for Zolgensma® (onasemnogene abeparvovec-xioi) for patients with spinal muscular atrophy (SMA), a rare neurological condition and a leading genetic cause of infant death. See what Dr. Mpofu had to say.

DocWire News: Can you detail for us the highlights of the research that was presented at the 2021 MDA Virtual Clinical & Scientific Conference on Zolgensma® for the treatment of spinal muscular atrophy (SMA)?

Dr. Shephard Mpofu: Thank you very much. Zolgensma is the only gene therapy for spinal muscular atrophy and the only spinal muscular atrophy treatment designed to directly address the genetic cause of the disease by really replacing the function of the missing or non-working survival motor neuron gene, SMN one, with a single one-time dose. It remains one of the most critical, transformative, essential, gene therapies that provides a lifetime benefit. At the virtual meeting, we presented a number of data, new Zolgensma data that really demonstrate age-appropriate development in children with spinal muscular atrophy. When used early, we also have real-world evidence that shows benefit in all children and durability five years post treatment, and importantly, how newborn screening enables a better outcome for a majority of these SMA kids.

DocWire News: How were these studies conducted?

Dr. Shephard Mpofu: Thank you very much. So we presented the pre-symptomatic study on patients with SMN one or two pick-up copies. Respectively, these fall into type one SMA and type two SMA. And we saw remarkable results where children were able to eat without any feeding tubes. And these children achieved age-appropriate milestones like sitting, standing and walking. Specifically, when we look at the two co-PI cohort, 80% of those patients achieved the primary efficacy endpoint, which was to sit for at least 30 seconds. And it was clear that the majority of those children achieved these milestones, which fall within the World Health Organization’s window for normal development. A third of these children were also able to stand and a third were able to walk. None of these children had any events in terms of needing ventilator support. Neither was there any feed chipping that was required and no serious adverse events.

When we move onto the patients with three copies, we also had remarkable achievement in more than 53% of children achieving the primary endpoint of being able to stand for at least three seconds. And 40% of kids in this study were walking independently and it has happened in the copy two cohort. These kids achieve these milestones in keeping with the World Health Organization’s development, milestone windows. Importantly, these results are unprecedented because when you look at kids with this type of disease in the natural history progression, these kids usually succumb to morbidity and mortality within two years. So seeing such a result provides the transformative, innovative impact of Zolgensma in spinal muscular atrophy.

DocWire News: Did any of these results surprise you?

Dr. Shephard Mpofu: These results add further weight and evidence to some of the studies we’ve done in different types of SMA, in symptomatic SMA, in multiple studies, across regions of Europe and the United States of America. And what’s remarkable is that the benefit risk remains consistent across the trials and the transformative efficacy of  a one-time essential treatment remains consistent across the various SMA types.

DocWire News: How big of a problem is SMA in America and is it often overlooked in your view?

Dr. Shephard Mpofu: SMA remains one of the most critical conditions that is occurring in about one in 10,000 children. This disease robs children of the ability to have any motor activity and children end up being unable to eat, to breathe or swallow and have a profound morbidity of requiring ventilation support and failure to thrive. It’s severe, debilitating, irreversible neuromuscular loss and death is a consequence. In the United States, there has been a fantastic improvement across multiple states with newborn screening and education by various advocacy groups. And we’re starting to see an improvement in diagnosis, which is also something we picked up in our real-world evidence data and from our registry, where it was very clear that kids who have been diagnosed by newborn screening compared to those that are diagnosed by clinical diagnosis are treated early, and importantly, do very well on Zolgensma without requiring any other SMA therapies.

DocWire News: What’s the overall impact you think this therapy can have in the fight against SMA?

Dr. Shephard Mpofu: This therapy is transformative in that it addresses the root cause of the genetic disease in SMA by replacing the missing survival motor neuron one gene. And this is only done as a one-off treatment and provides a lifetime of benefits. It also reduces the burden that happens with other therapies of having to go to a hospital multiple times and also the burden that’s around adherence in taking something daily.

DocWire News: Closing thoughts/remarks?

Dr. Shephard Mpofu: I just want to finish by saying that Zolgensma has constantly across multiple studies demonstrated the transformative efficacy in really showing age appropriate improvement in children with spinal muscular atrophy in most of the studies that we have done across the different types of SMA.