Zolgensma Shows Therapeutic Benefit, Anticholinergic Medications Increase MCI Risk, FDA Issues DRL For Zolmitriptan

October 10, 2020

Neurology News Network for the week ending October 10, 2020.

This week Neurology News Network covered the phase 3 trial of Zolgensma in patients with spinal muscular atrophy Type 1, data on the effects of anticholinergic medications on mild cognitive impairment, and the FDA discipline letter review sent for zolmitriptan.

Welcome to this special edition of Neurology News Network. I’m Marco Meglio. Please excuse our appearance this week as a majority of the US workforce, including the NeurologyLive team, moves to working remote as we come together to help reduce the spread of the novel coronavirus.

Newly released interim data from the phase 3 STR1VE-EU clinical trial of Zolgensma demonstrated the treatment’s significant therapeutic benefit in patients with spinal muscular atrophy Type 1. Patients within the study experienced event-free survival, rapid and sustained improvement in motor function, and motor milestone achievements. Evidence of these achievements was also found in patients with more aggressive disease at baseline compared to those in previous trials. The interim data was accurate as of December 31, 2019, and was presented recently as part of the World Muscle Society 2020 Virtual Congress. Achievement of milestones not previously observed in the natural history of SMA Type 1 was observed in 21 (65.6%) patients within the study. Among them, 6 (18.8%) achieved the primary end point by sitting independently for ≥10 seconds. The additional milestone of gaining head control was achieved by 20 (66.7%) patients. As well, 8 (25%) patients were able to roll back to sides and 1 patient was able to stand with assistance, crawl and walk with assistance.

Newly published data suggest that anticholinergic medications increase the risk of incident mild cognitive impairment and cognitive decline, with those effects significantly raised in individuals with genetic risk factors and cerebrospinal fluid based Alzheimer disease pathophysiological markers. Alexandra Weigand, graduate student, University of California–San Diego, and colleagues found that there was a significant aCH to AD-risk interaction. Data showed that aCH+ individuals who had positive APOE ε4 genotype had greater than a 2-fold increased risk for incident MCI relative to aCH- and ε4-. Weigand et al. concluded that the “findings of this study underscore the potential for negative consequences of aCH in older adults and support deprescribing trials, especially for individuals with elevated risk for AD.”

The FDA has issued a discipline review letter to Zosano Pharma in relation to its recent new drug application for its zolmitriptan (Qtrypa) transdermal microneedle system—also known as its adhesive dermally applied microarray (ADAM) platform—conveying some preliminary deficiencies the agency highlighted during its review of the application. The FDA accepted the new drug application for ADAM zolmitriptan in the acute treatment of migraine in March 2020. Zosano noted that as the comments are subject to change, the DRL does not reflect the final FDA decision on the application, though the approval of zolmitriptan by its PDUFA action date of October 20, 2020, is no longer anticipated as a result. Steven Lo, president and chief executive, Zosano, in a statement. “We believe Qtrypta represents an attractive therapeutic alternative for patients suffering from migraines and look forward to working with [the] FDA through the NDA review process.”

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