FDA Grants Fast Track Status to eRapa for Familial Adenomatous Polyposis Treatment

• Biodexa Pharmaceuticals' eRapa, a novel formulation of rapamycin, receives FDA Fast Track Designation for treating familial adenomatous polyposis (FAP), addressing a critical unmet medical need.
• Phase 2 trial demonstrates promising results with 89% of patients showing non-progression at 12 months and a 29% median reduction in polyp burden in the optimal dosing cohort.
• A phase 3 registrational study is planned, targeting approximately 140 high-risk FAP patients with a double-blind, placebo-controlled design.

The U.S. Food and Drug Administration has granted Fast Track Designation to Biodexa Pharmaceuticals' eRapa, marking a significant advancement in the treatment landscape for familial adenomatous polyposis (FAP). This designation acknowledges the urgent need for therapeutic alternatives beyond surgical intervention for FAP patients, who face inevitable progression to colorectal cancer without treatment.

Novel Drug Design and Mechanism

eRapa represents an innovative approach to rapamycin delivery, utilizing nanotechnology and pH-sensitive polymers to overcome the limitations of traditional rapamycin formulations. The drug targets the mammalian Target Of Rapamycin (mTOR) pathway, which plays a crucial role in cellular metabolism and proliferation. This pathway is notably overexpressed in FAP polyps, making it a promising therapeutic target.

Promising Phase 2 Results

The Fast Track designation was supported by compelling phase 2 data from a trial involving 30 adult patients across seven U.S. centers of excellence. The study evaluated three distinct dosing regimens:

• Cohort 1: 0.5 mg every other day
• Cohort 2: 0.5 mg daily every other week
• Cohort 3: 0.5 mg daily

The trial demonstrated particularly encouraging results in Cohort 2, where 89% of patients maintained disease non-progression at 12 months, achieving a median polyp burden reduction of 29%. Overall, 75% of patients across all cohorts showed non-progression at the 12-month mark, with a 17% median reduction in polyp burden.

Safety Profile and Patient Compliance

The drug demonstrated a favorable safety profile during the 12-month treatment period. While the study reported four related Grade 3 or higher adverse events and one serious adverse event, patient compliance reached 95%. Only one patient discontinued due to non-compliance, suggesting good tolerability of the treatment regimen.

Path Forward: Phase 3 Trial

Building on these promising results, Biodexa Pharmaceuticals is advancing to a registrational phase 3 study. The upcoming trial will employ a double-blind, placebo-controlled design, targeting approximately 140 high-risk FAP patients. The study will utilize the optimal dosing schedule identified in phase 2 - daily administration every other week.

The primary endpoint for the phase 3 trial will focus on progression-free survival, encompassing several critical measures including:

• Major surgery or referral necessity
• Polypectomy for advanced neoplasia
• Spigelman stage advancement
• High-grade dysplasia or cancer diagnosis
• All-cause mortality

This development represents a potential paradigm shift in FAP treatment, where currently, surgical resection of the colon and/or rectum remains the only available option.