Background

NurOwn™ comprises mesenchymal stem cells enriched from patients’ own bone marrow, propagated in the lab, and induced to secrete neurotrophic factors. The cells are transplanted back into the patients’ spinal cord and muscle, where the neurotrophic factors are expected to promote neuron survival, and slow down disease progression.

Published preclinical work describes microRNA profiling of MSC-NTF cells (Gothelf et al., 2017), and experiments demonstrating the safety of repeated injections of cryopreserved cells in mice (Gothelf et al., 2014). In mice, MSC-NTF transplant to the brain was reported to improve autism-related behaviors (Perets et al., 2017).

Findings

Two open-label safety studies were conducted between 2011 and 2014, involving 36 ALS patients who received NurOwn™ as one-time intramuscular or intrathecal injections, or both. After a six-month follow-up, the treatment was safe, and provided a possible clinical benefit (Jan 2016 news on Petrou et al., 2016).

A Phase 2, placebo-controlled study from May 2014 to July 2016 treated 48 early stage ALS patients with a one-time intramuscular and intrathecal administration of MSC-NTF cells. All patients underwent bone marrow harvest, followed by active transplants in 36 and placebo injections in 12. The study met its primary outcome of safety six months after transplant, but treatment did not change the clinical outcome of rate of decline on the on ALS-Functional Rating Scale (Berry et al., 2019). In a post hoc analysis, a rapid progressor subgroup of 21 patients showed hints of potential slowing of decline at one and three months after treatment.

In August 2017, a Phase 3 study randomized 196 patients to three intrathecal injections of NurOwn™ or placebo, spaced two months apart. The primary endpoint was the number of patients who met criteria for slowed disease progression on the ALSFRS-R six months after the first injection. Participants who finished the trial could continue treatment under an expanded access program. The trial finished in October 2020, and missed its primary endpoint of efficacy (Cudkowicz et al., 2022). A prespecified subgroup analysis suggested benefits in people with less-severe disease. CSF biomarkers of neuroinflammation, neurotrophic factors, and neurodegeneration improved after treatment. The company claimed an 11 percent reduction in CSF neurofilament light in treated patients (press release; July 2023 Gordon Conference poster).

In September 2022, the company filed a Biologicals License application with the FDA, which refused to review it (press release). This “Refusal to File” applies to applications the agency considers incomplete or to have inadequate scientific information to enable review. The company then used a “File Over Protest” procedure to force a review.

On September 27, 2023, an FDA Advisory Committee voted 17-1 against approving NurOwn™ (press release). In its briefing documents, the FDA said the application did not demonstrate effectiveness on primary or secondary endpoints. According to the agency's analysis, survival was worse in patients who received NurOwn™.

On October 18, the company announced it was withdrawing its licencing application in coordination with the FDA, and would discuss further development steps with the agency (press release).

NurOwn™ has also completed a Phase 2, open-label trial for multiple sclerosis (Cohen et al., 2023).

For details on NurOwn™ trials, see clinicaltrials.gov.