A new diagnostic drug approved in the EU for the visualisation of colorectal lesions during colonoscopies.
The results of our Methylene Blue MMX® pivotal phase III study were announced in November 2016.
The primary endpoint, adenoma detection rate or ADR, was attained: adenomas were found in 56.3 % of all patients when they took methylene blue MMX® prior to the endoscopy procedure, compared to 47.8 % of all patients using standard of care white light colonoscopy with high definition endoscopes (relative difference between arms: 17.71%).
ADR is a key colonoscopy quality indicator and is defined as the % of patients undergoing first-time screening colonoscopy who have one or more conventional adenomas detected and removed.
In the phase III clinical trial, the false positive rate (an important secondary endpoint) in the Methylene Blue MMX® arm was lower than in the WLHD. In the Methylene Blue MMX® arm, 356 subjects out of 485 subjects had an excision. Eighty-three of these subjects (23.3%) were false positives. In the WLHD arm, 326 out of 479 subjects had an excision and 97 of these subjects (29.7%) were false positives.
In February 2019, a Marketing Authorisation Application for Methylene Blue MMX® 200 mg tablets was filed with the European Medicines Agency.
In August 2020, the European Commission approved Methylene Blue MMX® for the visualisation of colorectal lesions during colonoscopies.
Methylene Blue MMX® U.S.
Our New Drug Application (NDA) for Methylene Blue MMX® was submitted to the U.S. Food and Drug Administration (FDA) in July 2017. In May 2018, we received a Complete Response letter (CRL) from the F.D.A. The CRL stated that while the outcome of the phase III trial had translated in a statistically significant outcome the outcome was not sufficiently ‘robust’ and recommended that we provide confirmation of effectiveness with a second phase III trial.
Discussions are ongoing with the FDA in relation to the confirmatory phase III trial required for U.S. registration.
Methylene Blue MMX® China
Another Phase III was conducted in China by Cosmo’s partner in the territory, China Medical System Holdings Limited (CMS). The study was a randomized, double-blind, placebo-controlled trial (placebo being in this case the standard of care, i.e. white light colonoscopy) run under good clinical practice (‘GCP’) in 22 sites across China. MB MMX was administered in conjunction with a bowel prep administered in split-dosing fashion. The study enrolled >1,800 patients in total and met the primary endpoint with very high statistical significance: in the overall FAS (Full Analysis Set), the proportion of patients with at least one histologically confirmed non-polypoid colorectal lesion was significantly higher in the Lumeblue ® group (51.0%) as compared with placebo (41.2%); (p< 0.0001). The study also showed a higher efficacy of Lumeblue in the proportion of patients with non-polypoid adenomas detected as compared to control (39.1% vs 31.2%; p<0.0003).