Update on Phase 2 Study of Nusinersen in SMA Infants Presented by Ionis Pharmaceuticals

Ionis Pharmaceuticals recently presented an update of its ongoing open-label Phase 2 clinical study of nusinersen, often called Ionis-SMN_,  in infants with spinal muscular atrophy (SMA) at the 2016 American Academy of Neurology meeting. According to the results, the investigational compound increased event-free survival, muscle function, and neuromuscular physiology, while no safety and tolerability concerns were identified.

“Nusinersen is the first drug in the clinic to target the underlying genetic cause of SMA and offers the promise of hope for this devastating disease,” said Richard Finkel, M.D., chief of the division of neurology, Department of Pediatrics at Nemours Children’s Hospital, in a news release.

SMA, a genetic disease that affects the control of muscle movement, is caused by the absence or defect of the survival motor neuron 1 (SMN1) gene, which in turn decreases the production of survival motor neuron (SMN) protein, essential for the healthy maintenance and survival of motor neurons.

Nusinersen is a drug designed to increased production of the SMN protein, by altering the splicing of SMN2, a gene closely related to SMN1, therefore compensating for the loss or defect of this gene. The drug, being developed through a partnership between Ionis Pharmaceuticals and Biogen, has been granted Orphan Drug status and Fast Track designation by the U.S. Food and Drug Administration and Orphan Drug status by the European regulatory agency.

The Phase 2 open-label study intends to evaluate the safety and tolerability of nusinersen in 20 infants with Type I SMA. The clinical efficacy endpoints include absence of progression to permanent ventilation or death (event-free survival); CHOP-INTEND motor function scores; electrophysiology measurements (compound muscle action potential, CMAP); and assessments of developmental milestones.

According to the presentation, nusinersen-treated infants live longer without the need for permanent ventilation, as compared to the natural history of these patients. Moreover, muscle function scores, in the CHOP INTEND score, have steadily increased and the infants have reached important function milestones such as unsupported sitting (eight patients), standing with or without support (five patients), and walking (two patients).

Importantly, CMAP measurements have increased from baseline, as opposed to the decline usually observed in these patients. The company reports no drug-related serious adverse events (SAEs) and the majority of SAEs were related to respiratory infections.  Most of the adverse events (non-SAEs) registered were mild or moderate in severity.

“The totality of these data in infants with SMA is encouraging, including the observed trends toward increases in muscle function as measured by CHOP INTEND and Hammersmith Infant Neurological Exam Motor Milestones,” Finkel said.

Ionis is currently conducting two Phase 3 studies to assess the safety and efficacy of nusinersen in infants and children, ENDEAR and CHERISH, respectively. The ENDEAR study is currently recruiting participants. The investigational drug is also being evaluated by Biogen and Ionis in four Phase 2 studies, including the one written about here.

“We remain very encouraged with the performance of nusinersen.  We and Biogen are committed to advancing nusinersen as rapidly as possible.  Together we are actively preparing for potential filing and commercial launch of nusinersen,” said B. Lynne Parshall, CEO at Ionis Pharmaceuticals.