In the ever-evolving landscape of biotechnology and longevity research, significant developments emerge from companies attempting to address key health challenges associated with aging. A recent announcement from BioAge Labs highlights both the potential and the risks of experimental therapies aimed at combating obesity, a condition that poses widespread health implications.

BioAge Discontinues Obesity Trial

On December 9, 2024, BioAge Labs announced that it would be halting its STRIDES Phase 2 clinical trial evaluating the investigational drug azelaprag for the treatment of obesity. This decision stemmed from safety concerns related to the occurrence of liver transaminitis in a subset of participants. Despite these occurrences not being associated with significant clinical symptoms, the potential risks have compelled the company to prioritize patient safety over further progression of the trial.

Understanding Transaminitis

Transaminitis refers to elevated levels of liver enzymes, specifically transaminases, which are critical for the liver's detoxification processes. The detection of transaminitis can signal underlying liver issues, raising caution among researchers and regulatory bodies alike. In the STRIDES trial, 11 out of 204 participants treated with azelaprag experienced these elevated enzyme levels, while no such elevations were recorded for participants treated solely with another drug, tirzepatide.

Study Group Participants Transaminitis Cases
Azelaprag Alone 204 11
Tirzepatide Alone Not specified 0

The Mechanism of Azelaprag

Azelaprag, a promising small molecule agonist, was designed to mimic the activity of apelin, a regulatory peptide associated with various health benefits, including exercise-induced advantages. By complementing the action of GLP-1 agonists like tirzepatide, azelaprag aimed to enhance metabolic processes that favor fat burning while retaining muscle functionality. The drug had previously exhibited potential in preclinical studies and early-phase trials to counteract muscle atrophy during sedentary periods.

Commitment to Safety

Dr. Kristen Fortney, the co-founder and CEO of BioAge Labs, underscored the company's dedication to patient safety, emphasizing the difficult decision to discontinue the trial:

“We made the difficult decision to discontinue the STRIDES Phase 2 study of azelaprag because it became clear that the emerging safety profile of the current doses tested is not consistent with our goal of a best-in-class oral obesity therapy.”

Future Directions for BioAge

In light of the discontinuation of the azelaprag trial, BioAge Labs remains focused on advancing its broader research agenda. The company is actively exploring various pathways related to metabolic aging and the development of therapeutic candidates addressing age-related diseases:

  • Therapies Targeting Neuroinflammation: The company continues to progress its novel brain-penetrant NLRP3 inhibitor, aimed at managing neuroinflammation, which is intricately linked to metabolic and neurodegenerative diseases.
  • Investigational New Drug Submission: BioAge anticipates submission of an IND for the NLRP3 inhibitor by the second half of 2025.

Dr. Fortney reassured stakeholders, stating, “We remain committed to our focus on developing therapies for metabolic aging.” As BioAge pivots to account for the lessons learned from the STRIDES trial, it stands at the forefront of a critical juncture in longevity research.

Conclusion

The case of BioAge underscores both the innovative spirit and the inherent risks involved in the pursuit of cutting-edge therapies for age-related conditions. As the landscape of longevity biotechnology continues to shift, the outcomes and implications of such trials will play a pivotal role in shaping future therapeutic strategies. The quest for effective treatments for obesity and metabolic aging remains a formidable challenge, demanding rigorous evaluation and thoughtful consideration of safety and efficacy.

References

This article references data and findings from Lifespan.io in relation to ongoing research in the field of longevity and metabolic health.