BY DAVID MELAMED, PHD

Seneca Biopharma announced that work is underway to advance NSI-566, its leading stem cell treatment candidate, into a Phase 3 study in people with amyotrophic lateral sclerosis (ALS).

The decision followed a meeting with the US Food and Drug Administration (FDA), and is supported by data collected from a Phase 1 (NCT01348451) and Phase 2 (NCT01730716) clinical trial.

During the March 10 meeting, the FDA provided guidance on how to best design and conduct the Phase 3 trial. Seneca is now developing the trial’s protocol, which will be reviewed by the FDA before it might open.

“This represents a major step forward in getting our potentially beneficial therapy to patients who suffer from this devastating disease,” said David Recker, chief medical officer for Seneca, in a press release. “We received significant guidance from FDA regarding an acceptable trial design and are in the process of developing the protocol for further review.”

NSI-566 is an investigational neural stem cell therapy that uses human spinal cord stem cells (HSSCs). Stem cells are unique in that they have the capacity to differentiate into many types of specialized cells during development.

When injected into the spinal cord, NSI-566 differentiates into types of neurons found in adults. They surround and support motor neurons damaged by ALS, by integrating into the neural network and forming connections (synapses) with the patient’s own neurons. They also secrete certain molecules that promote motor neuron growth and survival.

The two previous clinical trials were primarily designed to test the safety of NSI-566 in ALS patients, and each showed promising results. Both trials are now in a follow-up stage, with researchers monitoring patients to determine the safety and efficacy of the treatment on a long-term basis.

When analyzing the trials’ data, researchers compared the clinical outcome and survival of ALS patients for up to three years with data collected from previous ALS clinical trials, including one investigating ceftriaxone (Rocephin) and 23 others that are cataloged in the PRO-ACT database.

Measurements included ALSFRS-R, a functional rating scale based on a questionnaire, and ALS/SURV, a statistical analysis that combines survival and functional outcomes.

After two years, ALSFRS-R and ALS/SURV scores were significantly higher in people given NSI-566 transplants than in the comparison groups. Survival did not differ significantly between groups.

NSI-566 was granted an orphan drug designation by the FDA, which offers Seneca an extended period of exclusivity in the marketplace, as well as financial incentives for clinical trial investigations.

“We are very pleased with the outcome of the discussions,” said Ken Carter, executive chairman of Seneca. “We look forward to working closely with the Agency [FDA] on finalizing the design of a Phase 3 trial for this devastating disease.”

As NSI-566 is designed to replace damaged neurons, the treatment is also being investigated for chronic spinal cord injury (cSCI), and for restoring motor function after paralysis due to an ischemic stroke.