- Minerva Neurosciences reported positive topline results from a mid-stage study of its schizophrenia drug nearly a year ago, and now that trial’s design is largely serving as a template for an upcoming investigation.
- MIN-101 is moving into late-stage testing on the heels of an end-of-Phase 2 meeting between the biotech and the Food and Drug Administration. The company plans to kick off the pivotal, Phase 3 trial in the second half of this year.
- In many ways, the newly-minted trial mirrors its Phase 2b predecessor. It will be double-blinded and randomized, testing MIN-101 against placebo in patients with moderate-to-severe negative symptoms. The studies also share the same primary endpoint: improvement from baseline for a particular set of schizophrenia expressions dubbed negative symptoms.
Minerva will have to balance the inherently slippery nature of schizophrenia trials with the need to quickly get MIN-101 to market for maximum return on investment; the drug, in-licensed from Mitsubishi Tanabe Pharma Co., loses its composition of matter patent exclusivity in Europe and the U.S. in 2021.
The problem Minerva runs into, and one that is common among central nervous system drug developers, is that its disease target is incredibly difficult to treat. The FDA hasn’t greenlit any therapies for schizophrenia’s negative symptoms, which include reductions in speaking or displays of emotion, and are often more difficult to diagnose.
As a result, there have been many failures in the clinical space. Last September, for instance, Intra-Cellular shares plummeted after its schizophrenia candidate failed in a late-stage study.
Where Minerva benefits, though, is in its drug’s successful stint in mid-stage testing. In Phase 2b, participants in the experimental arms of the study had significantly improved negative symptoms versus those receiving placebo, according to their scores from different parts of the Positive and Negative Syndrome Scale (PANSS), a tool for measuring the severity of a patient’s schizophrenia.
Investigators also noted the frequency and seriousness of adverse events were about the same for those receiving placebo or treatment, with just two of the 162 patients on MIN-101 discontinuing the study for cardiac reasons.
That study enrolled 244 participants who met a number of prerequisites, such as maintaining stable positive and negative symptoms for three months before their enrollment, and tested two daily doses of MIN-101, 32mg and 64mg. Following the 12-week phase of blinded testing, the trial’s patients could opt into a 24-week, open-label extension period.
Minerva expects to enroll more patients in the Phase 3 trial and use more sites, about 500 and 60, respectively, than it did in the Phase 2b trial. The optional extension period of the new study will also be longer at 36 weeks. Other than those elements, the trials are relatively similar.
"The company's Phase 3 trial design is intended to replicate the experience of 'real world' clinical practice in schizophrenia," Minerva said in a May 15 statement. "Many patients are dissatisfied and not well served by continuous antipsychotic treatment as evidenced by poor compliance with medications.”
A strong performance in Phase 3, combined with the positive results from Phase 2 testing, may be enough evidence to file a New Drug Application with the FDA, according to the company. It did not, however, elaborate further about a possible timeline for that submission in the statement.