ideasIdea
Select cachexia trial patients by the hormone driving their wasting
Wasting has several causes. Measuring the specific hormone in each patient's blood would put the right patients into the right trial instead of mixing everyone together.
Cachexia trials have historically enrolled by weight loss criteria alone, mixing inflammatory, anorexic, hypermetabolic and mechanical causes. Plasma GDF-15, interleukin-6, C-reactive protein and resting energy expenditure define mechanistically distinct groups. Enriching for high GDF-15 in anti-GDF-15 trials, and for high interleukin-6 in anti-inflammatory trials, is straightforward and cheap.
Hypothesis
Biomarker-stratified enrolment increases the observed treatment effect size in cachexia trials by at least 50% relative to unselected enrolment, converting historically borderline results into clear ones.
Rationale
Mechanistic stratification rescued many oncology drugs that failed in unselected populations. Cachexia is arguably the least stratified field in oncology despite having measurable, causally relevant plasma markers.
What would test it
Retrospectively stratify banked samples from completed cachexia trials by GDF-15 and interleukin-6 and test for treatment-by-biomarker interaction; if present, mandate stratification prospectively.
Maturity
speculative
Who has to act
industry
Cost to try
Small (under $1M)
Years to first evidence
4
Bottlenecks it attacks
- Cachexia, toxicity and the limits of the patient · Patients often die of wasting or cannot tolerate the doses that would work. Treating the patient, not just the tumour, lags far behind.
- Biomarkers are not validated or standardised · Tests that decide who gets a drug are often not validated prospectively and are measured differently in every lab.
- Trial design, endpoints and cost · A phase 3 trial takes years and hundreds of millions of dollars, and often answers a question that has already moved on.