Innate reveals "distressing" MS trial results

Biotech company Innate Immunotherapeutics (ASX:IIL) reluctantly announced on Tuesday that its MS therapy MIS416 showed no meaningful or statistically significant results in a recent Phase 2B trial, with the company’s shares dropping a whopping 92% as a result.

MIS416 is a microparticle derived from bacteria, combined with two immune-modifying molecules. It acts to stimulate a specific range of responses in one branch of the immune system, known as the innate immune system.

The randomised, double-blind, placebo-controlled trial was intended to evaluate the efficacy, safety, tolerability and immune pharmacodynamics of MIS416, compared to placebo, in subjects with secondary progressive multiple sclerosis (SPMS). The trial was conducted at five sites in Australia and two in New Zealand, with a total of 93 subjects — 62 to receive MIS416 and 31 to receive a saline placebo — receiving intravenous dosing once a week for a year. There were 17 (27%) subjects who prematurely discontinued treatment in the MIS416 group and four (13%) in the placebo group.

To determine the efficacy of MIS416 relative to placebo on measures of neuromuscular function, assessments were carried out at baseline, at quarterly intervals during the trial and at end of dosing. The assessments comprised measures of upper extremity function and strength, walking speed and distance, visual acuity and cognitive processing speed. An analysis of all 93 patients found no overall clinically meaningful or statistically significant differences across the multiple measures of neuromuscular function assessed.

The efficacy of MIS416 relative to placebo was meanwhile based on patient-reported outcome questionnaires comprising the Multiple Sclerosis Impact Scale, the Neurological Fatigue Index for patients with multiple sclerosis and the Brief Pain Inventory. Again, analysis showed no overall clinically meaningful or statistically significant differences in patient-reported outcomes. Analysis of the expanded disability status scale (EDSS) score showed no change between the two groups at the ITT population level, while analysis of percentage brain volume change, as assessed by MRI, showed no significant difference between the two groups.

The trial did not fare much better when it came to safety and tolerability, with at least one treatment-related adverse event in 60 of the 63-subject (97%) MIS416 group and 23 of the 31-subject (74%) placebo group. There was at least one treatment-related serious adverse event in 16 subjects (26%) in the MIS416 group and five subjects (16%) in the placebo group. Six subjects in the MIS416 group (9.7%) withdrew from the study due to at least one adverse event (which may or may not have been treatment related) and two subjects (6.5%) withdrew from the placebo group.

“These results are a shock and definitely not what we were expecting based on our previous clinical experience with MIS416 and the reporting of treatment benefits we have received from many compassionate use patients over an extensive eight-year period,” said Innate Immunotherapeutics CEO Simon Wilkinson. “These data will be as distressing to them as they will be for all the stakeholders who were relying on the outcome of this study.”

Chief Scientific Officer Gill Webster said the company will be sponsoring an analysis of the trial results at the patient level to see if there is a group of clinical responders which might not be evident from the population-based analysis. If there is such a group, the immune pharmacodynamics monitoring of the patients that took place during the study may identify a biomarker that could be used to pre-identify responders in any future clinical development of MIS416. If, however, analysis bears out the apparent clinical failure of MIS416 in patients with SPMS, the company will be reviewing whether there are grounds for further clinical development of MIS416 in SPMS or another indication. Innate Immunotherapeutics will also be reviewing the future of its MIS416 Compassionate Use Program, though the company has received clinical advice that there is no immediate need to halt the program.

Innate Immunotherapeutics (ASX:IIL) shares dropped on Tuesday from a high of $0.071 to a low of $0.031, signifying a loss of 92.34%. They have since climbed back and were trading at $0.064 as of around 2 pm on Friday.