2014 SMA Researcher Meeting Summary: Clinical Trials

We will be posting a series of summaries from our 2014 researcher meeting, highlighting some of the most interesting new developments and discoveries presented there. This is the last of four total updates, and the second of two in drug discovery and clinical trials.

This session was moderated by Douglas Kerr, MD, PhD, Biogen Idec.

Clinical Research and Trial Updates

The SMA Researcher Meeting concluded with six talks: three on clinical trial outcomes and three on clinical trial updates. In clinical trials, outcomes are the critical measurements that evaluate improvements from drug treatments.

The first talk was given by Amy Pasternak, in collaboration with Dr. Basil Darras at Boston Children’s Hospital. Their group has been assessing the Pediatric Evaluation of Disability Inventory (PEDI-CAT) outcome for SMA. PEDI-CAT is a caregiver-reported outcome measure designed to evaluate and measure change in daily functional activities .

Next, Kristin Krosschell of Northwestern University described electrophysiological and motor function outcomes for infants with SMA. In the motor unit number estimation (MUNE) and compound muscle action potential (CMAP) tests, values declined with age and correlated with loss of motor function, providing support for these measures as outcomes in SMA clinical trials.

Lindsay Alfano of Nationwide Children’s Hospital described a novel measure called Abilities Captured Through Interactive Video Evaluation Mini (ACTIVE-Mini) to quantify movement in infants with SMA type I. The study provided preliminary data on the reliability and validity of this assessment. In the future, this could produce objective measurements of movement abilities in infants as young as 15 days old.

The meeting closed with three clinical trial updates. The first talk was from Cure SMA-funded researcher Dr. Stephen Kolb at OSU. Dr. Kolb spoke on the SMA Infant Biomarker Study in the Immediate Postnatal Period, the premier clinic study of the NINDS-sponsored NeuroNEXT Clinical Trial Network.

This study will identify important indicators, called biomarkers, that might help us measure how well a treatment is working in very young babies. The study is looking at these biomarkers in infants with SMA and in healthy infants, so we can compare results. In September, Dr. Kolb’s team announced that the NeuroNEXT biomarker study is fully enrolled.

Infants are studied every three months for their first year of life and every six months until their second birthday. Motor function and putative electrophysiological and molecular biomarkers are being studied to provide a data set that can be used to inform the design of future clinical trials in infants with SMA.

Next, Dr. Eric Dessaud of Trophos presented results of a Phase II study to assess the safety and efficacy of olesoxime in 3-25 year old SMA patients. Patients were randomized to olesoxime or matching placebo in a 2:1 ratio. Treatment duration was for 104 weeks. The trial results showed that loss of function, assessed by the primary endpoint of the MFM motor scale, was prevented for two years in olesoxime-treated patients, with fewer disease-related adverse events.

The meeting closed with a talk from Dr. Kathie Bishop from Isis Pharmaceuticals, who gave an update on the Clinical Development Of ISIS-SMNRx. An open-label, multiple ascending-dose study was conducted to evaluate the safety, tolerability, and efficacy of ISIS-SMNRx in children with SMA type II or III.

Multiple doses of ISIS-SMNRx (3 dose levels) were delivered intrathecally (through an injection in the lower back) to medically stable SMA patients 2-15 years of age (n=25). Subjects were dosed 2-3 times over 3 months and then followed for 6 months post-dosing and monitored for drug safety and tolerability, SMN protein levels, and clinical outcome measures.

Overall, no safety or tolerability concerns related to ISIS-SMNRx were identified, and repeated intrathecal injections were well tolerated in children with SMA. Cerebrospinal fluid (CSF) and plasma drug levels were dose-dependent and predictable. The Modified-Hammersmith motor function scores indicated an improvement in motor function at all doses levels, with time and dose dependency. In October 2014, Isis released a new update on this trial, as well as for their Phase II trial in infants.

A Phase III trial in infants has already begun recruiting. A Phase III trial in children is planned for later this year.

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