The U.S. Food and Drug Administration has given positive feedback to MediciNova’s Phase 3 developmental plan for its investigational therapy ibudilast (MN-166) for amyotrophic lateral sclerosis (ALS).
Following the FDA’s guidance and suggestions, the company will design a trial that determines the maximum benefit of the treatment, and provides enough information for a potential marketing application submission.
“We are excited to receive the green light from FDA to proceed with Phase 3 development of MN-166 for ALS. We will finalize the study design according to FDA’s feedback,” Yuichi Iwaki, MD, PhD, president and CEO of MediciNova, said in a press release.
To achieve the best result possible, the regulatory agency suggested that a future Phase 3 trial should include a broader ALS population. Randomization and data analysis should then be stratified according to a patient’s disease severity at the start of the study.
If researchers demonstrate a statistically significant benefit of ibudilast in patients’ functional activity over a placebo, as determined by changes in the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) total score, the agency believes that further trials may not be necessary.
The FDA also noted that, because ALS is a rare disease, flexibility in the requirements for a marketing application may exist.
The trial, called IBU-ALS-1201, randomly assigned 60 ALS patients to 60 mg daily of ibudilast or a placebo, along with daily Rilutek. For each patient receiving the placebo, two received the active treatment.
Results showed that adding ibudilast to Rilutek significantly improved functional activity, quality of life, and muscle strength, compared with Rilutek alone. In addition, the combination delayed disease worsening overall and improved the survival rates of these patients.
No safety issues regarding ibudilast were reported, but safety will continued to be addressed in additional clinical studies.
MediciNova is now studying a higher dose of ibudilast — 100 mg daily — as a stand-alone therapy for ALS patients. The Phase 1/2 trial (NCT02714036) has already completed patient enrollment and is underway at the Massachusetts General Hospital in Boston and South Shore Neurologic Associates in New York.
This study is also evaluating several markers of neurological inflammation measured by blood biomarkers, as well as the effect of the treatment on disease progression and patient outcomes.
Ibudilast is a small molecule that inhibits the activity of the phosphodiesterase-4 and -10 enzymes and the macrophage migration inhibitory factor. This reduces the activity of immune cells in the brain and increases the production of neurotrophic factors that support the survival and growth of motor neurons.
Ibudilast is already marketed in Japan and Korea as a treatment for post-stroke complications and bronchial asthma. MediciNova is currently exploring its potential in neurological conditions, such as ALS, progressive multiple sclerosis, and substance addiction.
The FDA has granted fast track status and orphan drug designation to ibudilast for the treatment of ALS. These are expected to expedite and support its clinical development and review, assisting in ibudilast’s potential approval.