eRapa Recieves FDA Fast Track Designation for Familial Adenomatous Polyposis

Credit: US Food and Drug Administration

The US Food and Drug Administration has granted Fast Track Designation to Biodexa Pharmaceuticals’ eRapa, a proprietary encapsulated form of rapamycin being developed for the treatment of familial adenomatous polyposis (FAP).¹

According to a February 10, 2025, press release, the designation was requested based on the potential for eRapa to address an unmet medical need for FAP, which universally leads to colorectal cancer if left untreated. Currently, the only treatment option for FAP is surgical resection of the colon and/or rectum.¹

eRapa is a proprietary oral tablet formulation of rapamycin, also known as sirolimus. Rapamycin is a mammalian Target Of Rapamycin (mTOR) inhibitor, and mTOR has been shown to play a significant role in the signaling pathway that regulates cellular metabolism, growth, and proliferation and is activated during tumorgenesis. Importantly, mTOR has been shown to be over-expressed in FAP polyps.¹

Through the use of nanotechnology and pH sensitive polymers, eRapa is designed to address the poor bioavailability, variable pharmacokinetics, and toxicity generally associated with the currently available forms of rapamycin, which is approved in the US for organ rejection in renal transplantation.¹

eRapa’s Fast Track Designation was supported by phase 2 data demonstrating its safety and tolerability in 30 adult patients with a median age of 43 years with intact colon (n = 6) or post-colectomy and ileorectal anastomosis and ≥ 10 adenomas in the rectal remanent (n = 24).^1,2

The open-label study was conducted in 7 US centers of excellence and sequentially enrolled participants into 3 dosing cohorts of 10 patients each for a 12-month treatment period: 0.5 mg every other day (cohort 1); 0.5 mg daily every other week (cohort 2); and 0.5 mg daily (cohort 3). Upper and lower endoscopic surveillance occurred at baseline and after 6 months.²

The primary endpoints were safety and tolerability of eRapa and percentage change from baseline in polyp burden at 6 months, as measured by the aggregate of all polyp diameters. Of note, patients continued to receive treatment and monitoring for 12 months.²

At 12 months, 75% of patients were deemed to be non-progressors at 12 months with a median reduction in polyp burden of 17%. In cohort 2, 89% of patients were deemed non-progressors at 12 months with a median reduction in polyp burden of 29%.²

Over the course of 12 months, there were 4 related ≥ Grade 3 and 1 related Serious Adverse Event reported during the trial and 95% compliance rate at 12 months. Additionally, a single patient was removed from the trial due to non-compliance.¹

According to the release from Biodexa, the dosing given in cohort 2 – daily every other week — is the preferred dosage regimen for the upcoming registrational phase 3 study, which is planned to be a double-blind placebo-controlled design recruiting approximately 140 high-risk patients diagnosed with germline or phenotypic FAP.^1,2

At the time the 12-month phase 2 data was announced in June 2024, Biodexa indicated the primary clinical endpoint was likely to be the first progression-free survival event, including major surgery or referral thereto, polypectomy for advanced neoplasia, advancement of Spigelman stage, diagnosis of high-grade dysplasia or cancer and death from any cause.²

References

1. ^{Biodexa Pharmaceuticals. Biodexa Receives US FDA Fast Track Designation for eRapa in Familial Adenomatous Polyposis. February 10, 2025. Accessed February 10, 2025. https://biodexapharma.com/biodexa-receives-us-fda-fast-track-designation-for-erapa-in-familial-adenomatous-polyposis/}
2. ^{Biodexa Pharmaceuticals. Biodexa Announces Positive Phase 2 Clinical Trial Results of eRapa™ at 12 months in Familial Adenomatous Polyposis (FAP). June 24, 2024. Accessed February 10, 2025. https://biodexapharma.com/biodexa-announces-positive-phase-2-clinical-trial-results-of-erapa-at-12-months-in-familial-adenomatous-polyposis-fap/}