Aphaia Pharma Reports Positive Phase 2 Trial Results for Prediabetes Drug

Aphaia Pharma, a clinical-stage biopharmaceutical company, announced the successful achievement of the primary endpoint in their Phase 2 trial evaluating the oral glucose formulation APHD-012 for prediabetes treatment. The trial demonstrated a significant improvement in glucose tolerance in individuals with a pathological Oral Glucose Tolerance Test (OGTT) after six weeks of administration compared to a placebo. The study also confirmed that APHD-012 was well tolerated, with no serious adverse events reported.

The trial results provide proof-of-concept for Aphaia’s oral glucose formulation, which is designed to restore endogenous nutrient-sensing pathways in the gastrointestinal tract. The study included individuals who were healthy, prediabetic, or diabetic and followed a randomized, double-blind, placebo-controlled, multi-center design. Participants received either a 12g dose of APHD-012 or a matching placebo daily for six weeks, followed by a four-week washout period and subsequent crossover to the opposite treatment for another six weeks.

Significant results from the trial include:
- In the overall group, APHD-012 reduced OGTT blood glucose levels at 120 minutes post-challenge from 9.0 ± 0.6 to 7.9 ± 0.6 mmol/L (n=23, p=0.01); placebo treatment showed no significant effect (8.8 ± 0.4 mmol/L versus 8.5 ± 0.6 mmol/L; p=0.33).
- A larger effect size was observed in prediabetic patients with APHD-012 reducing glucose levels from 8.7 ± 0.4 to 6.8 ± 0.5 mmol/L (n=12, p=0.003); placebo had no significant impact (8.6 ± 0.4 versus 8.2 ± 0.6 mmol/L; p=0.25).
- Improving glucose tolerance was also evident through the reduction in OGTT area under the curve (AUC 0-120 minutes) for prediabetic patients from 1261 ± 47 to 1163 ± 36 min*mmol/L (p=0.004, n=12); the placebo treatment did not significantly affect AUC (1250 ± 45 to 1225 ± 53 min*mmol/L; p=0.47).
- For diabetic patients, APHD-012 lowered OGTT blood glucose levels at 120 minutes post-challenge from 13.2 ± 0.7 to 11.6 ± 0.5 mmol/L (n=5, p=0.0006); the placebo was ineffective (11.4 ± 0.5 versus 12.0 ± 0.6 mmol/L; p=0.59).

The safety profile of APHD-012 was positive, with 13 adverse events (AEs) reported in 8 subjects (27%) during the six-week treatment, compared to 7 AEs in 5 subjects (17%) taking the placebo. No serious AEs occurred during the study.

Steffen-Sebastian Bolz, M.D., Ph.D., Chief Scientific Officer of Aphaia Pharma, expressed excitement over the findings, emphasizing the potential of APHD-012 in managing prediabetes and its broader implications for treating other metabolic conditions like diabetes and obesity. He highlighted the importance of the upcoming data from the ongoing Phase 2 trial in individuals with obesity to guide future strategic decisions.

Christian Sina, M.D., the principal investigator of the trial and a professor of Medicine at the University of Luebeck, praised the results, noting the significance of a drug showing effectiveness in OGTT with a favorable safety profile. He emphasized the urgent need for effective therapies to prevent or delay type 2 diabetes, given the limited success of current lifestyle interventions.

APHD-012, Aphaia’s lead drug candidate, is engineered to target specific parts of the small intestine to activate nutrient-sensing pathways and stimulate the release of enteric hormones that regulate glucose metabolism, appetite, and energy expenditure. This includes hormones like glucagon-like-peptide 1 (GLP-1) and peptide tyrosine-tyrosine (PYY), among others.

Aphaia Pharma is dedicated to developing precision-targeted drug formulations to restore endogenous hormone release for the treatment of metabolic disorders such as obesity and related diseases. The company’s technology platform allows for the potential development of treatments for various disease patterns. Additional results from the ongoing Phase 2 trial evaluating APHD-012 in individuals with obesity are anticipated in the second half of 2024.