Israeli cell therapy specialist Neurogenesis Ltd., said new phase II data has shown that treatment with its autologous cell therapy candidate NG-01 in progressive multiple sclerosis (MS) patients led to an 80% to 90% reduction in disease progression at 12 months compared to a pretreatment period and a 90% reduction in relapses compared to placebo-treated patients.
“The results are highly significant in all parameters and show much more efficacy than any other treatment in progressive MS,” Dimitrios Karussis, lead principal investigator and director of the MS Center at Hadassah Medical Center in Jerusalem, told BioWorld.
Karussis explained that there are currently very effective medications for stopping relapses and slowing the progression of relapsing remitting MS, but not very successful ones for progressive disease. The only registered treatment for primary progressive MS, Roche Holding AG’s Ocrevus (ocrelizumab), slows down the progression rate by 20% to 25%, he said. For secondary progressive MS, Novartis AG's Mayzent (siponimod) also slows progression by about 20%, he added.
To determine whether NG-01 might one day prove more effective, the phase II study enrolled 48 people with progressive MS who were randomized into three groups and assigned to receive either an intrathecal or I.V. dose of NG-01 or a placebo injection. The study lasted for 14 months and met all of its primary endpoints.
Researchers said no serious treatment-related safety issues were detected. Only 6.7% and 9.7% of patients experienced disease progression in the intrathecal and I.V. NG-01 treatment groups, respectively, compared to 41.9% in the placebo group (p=0.0003 and p=0.0008). Also, 58% of the patients treated intrathecally with NG-01 did not show any evidence of disease activity during the entire the treatment period, compared to 9.7% in the placebo treated group (p<0.0001).
Trial participants treated with NG-01 demonstrated a significant improvement in walking ability, as measured by 25-foot walking time (P=0.0017), the company said. Investigators also found that intrathecal administration of NG-01 was also more efficacious than I.V. delivery in several key parameters of the disease, such as relapse rate (89% decrease in the relapse rate), functional MRI, monthly changes of the MRI T2 lesion load and the 9-hole peg test vs. the placebo-treated group.
“The strengths of our trial include the inclusion of patients with active progressive multiple sclerosis, for which existing immunotherapies are usually ineffective, the double-blind design making this the first randomized controlled trial comparing intrathecal versus intravenous methods of NG-01 administration and single versus repeated treatment; and the robust, though short-term (6-12 months), clinical benefits observed in several disease activity parameters, including newer biomarkers, such as functional MRI-network connectivity, OCT, and cognitive testing,” Karussis told BioWorld.
Separately, he said this trial provides encouraging results and suggests a potential for a new approach that may not only slow down the progression of the disease but even induce improvement and promote repair mechanisms in progressive MS.
Following the encouraging phase II data, Neurogenesis CEO Tal Gilat told BioWorld the next step is to start a multicenter phase IIb in the U.S., Europe and Israel, which “will focus on improvement and repair in progressive MS patients,” he said. The company has already had a pre-IND meeting with the FDA.
NG-01 is Neurogenesis’ lead product. Besides being tested in progressive MS patients, it was also tested in two phase IIa trials in amyotrophic lateral sclerosis.
“Given our positive outcomes in two open-label trials in ALS with long follow-up periods, we are now considering what would be the best route to clinically advance NG-01 also for the ALS indication,” Gilat said.
The Jerusalem-based biotech focuses on developing cell therapies for neurodegenerative diseases with an approach for sustained delivery of high levels of remyelinating growth factors using the patient’s own stem cells.
Neurogenesis licensed NG-01 from Hadasit, the technology transfer company of Hadassah Medical Center, to advance the cell therapy candidate.
The biotech used its Neuralyzed Cell platform to identify, culture and enhance a subpopulation of bone marrow cells towards remyelinating cells that also possess neurotrophic immunomodulatory and neuroprotective properties. The NG-01 cell population is injected directly into the central nervous system through the cerebrospinal fluid, where the cells home-in on a damaged area, take up residence and produce large amounts of neurotrophic factors.
“Neurogenesis helped optimized the cell manufacturing process to become highly efficient and scalable,” Gilat said. “By manufacturing the required treatments from one bone marrow extraction, storing the vials in cryopreservation, and shipping them to the hospital only when required, we enable high consistency of quality across injections, while lowering manufacturing costs as well as enabling treatment schedule flexibility.”