SMA, Migraine Data Lead Neuro Highlights from AAN Meeting

Xconomy National — 

The American Academy of Neurology meeting in Philadelphia is rolling on through the end of this week. There has been plenty of news to digest already. New clinical data could herald cutting-edge treatments for migraine, the rare disease spinal muscular atrophy, the deadly neurological disorder amyotrophic lateral sclerosis, and more.

Xconomy previewed the conference last week. Today we’re circling back to sort through the news and put it in context.


The treatment landscape for spinal muscular atrophy, or SMA, a rare and potentially lethal genetic disease, is about to change. Until the 2016 approval of nusinersen (Spinraza) from Biogen (NASDAQ: BIIB), there were no approved medicines to help slow the progressive weakness that characterizes the disease. Infused into the spine a few times a year, for life, Spinraza has shown it works for people with multiple forms of SMA. It is now the standard of care for the disease and generated $1.7 billion for Biogen last year.

But other treatments are coming, which, as Xconomy reported last week, will present doctors and payers with tough logistical and economic questions. The two treatments under the microscope at AAN are Zolgensma, from Novartis (NASDAQ: NVS), and risdiplam, from Roche and partner PTC Therapeutics (NASDAQ: PTCT).


The gene therapy ideally would provide the same benefits as Spinraza, but through a single long-lasting infusion. The FDA could approve Zolgensma this month.

Prior to AAN, Zolgensma has shown promise in Type 1 SMA, the deadliest form of the disease, diagnosed within six months of birth. On Sunday, the Basel, Switzerland-based pharma offered more Type 1 data from the STR1VE study. But it also offered the first glimpse of studies meant to show that, like Spinraza, Zolgensma can help others with the disease as well. The STRONG study is testing Zolgensma in Type 2 patients who could sit, but not stand or walk, at the start of the study. Pre-symptomatic patients got Zolgensma in a study known as SPR1NT.

Both trials compare Zolgensma’s effects to historical data, not a placebo. Those effects are measured via tests (CHOP-INTEND, HFMSE, and Bayley-III Gross Motor Milestones) that assess physical abilities and developmental milestones. One key milestone is whether patients are alive and not using a ventilator at the age of 14 months.

Patients in STRONG were followed a median of 6.5 months after treatment, in SPR1NT, 5.4 months. At this point, neither study has lasted long enough to assess Zolgensma’s promise of a long-lasting treatment, let alone a cure. The data are being closely watched, despite not including results from the highest dose in the STRONG study. Here’s a snapshot.

STRONG: Novartis put Type 2 patients in two groups: babies six to 24 months of age, and young children two to five years old. For babies, the study’s main goal is to help them stand or walk without support for more than three seconds. For young children, the goal was a positive change on the HFMSE.

Two of the 16 babies evaluated thus far can stand without help. One of them can walk. One of the 12 young children can walk with assistance. All the patients, at minimum, maintained their abilities from the study’s start, like rolling over, controlling their head, and more. Seven of the babies and three of the young children gained an ability. All the patients are still alive, and those who have gone through HFSME evaluations have seen their scores increase.

The only serious side effects were a temporary spike in liver enzymes, a common occurrence in gene therapy trials.

SPR1NT: Novartis enrolled 18 newborn patients who had yet to show symptoms and had either two or three copies of the SMN2 gene, a predictor of disease severity. The more SMN2 genes a person has, the more mild their disease will be. (SMN stands for spinal motor neuron.)

Thus far, all 18 patients are alive. Four of eight patients with two SMN2 copies could sit independently following treatment, and one could stand with assistance. Historical data suggest these patients would never hit those goals otherwise. They also saw their CHOP-INTEND scores increase, a sign of improvement that wouldn’t be expected without treatment. No serious side effects seen were attributed to the gene therapy.

Alex Fay, a pediatric neurologist at UCSF Benioff Children’s Hospital in San Francisco, CA, cautions that it will probably take more time to “see the full range of benefit” of Zolgensma in Type 2 and 3 patients. He also notes that older patients appear more likely to have an immune defense against the treatment, which could be a problem. Still, “I think the take-home points are that gene therapy seems to be effective and safe across subtypes of early-onset SMA, efficacy appears comparable to Spinraza’s, and that there will likely be a continued role for Spinraza in treating patients with SMA,” he said after looking over the data.

Using Spinraza and Zolgensma together, particularly in pre-symptomatic patients, could be more beneficial, he adds. But combination therapy hasn’t been tested and the costs would be significant.


Like Spinraza and Zolgensma, risdiplam is meant to boost the production of the SMN protein that SMA patients lack. (Without it, motor neurons in the spinal cord waste away.)

The oral risdiplam could be more convenient. Susan Begelman, the head of medical affairs for neuroscience for Roche’s Genentech unit, notes that … Next Page »

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