Failed pivotal study? You can still have breakthrough therapy status — FDA signals to Resverlogix
A small Canadian biotechnology company has convinced the FDA to reward its sole experimental drug breakthrough therapy status as a preventative therapy for major adverse cardiac events, despite a failed late-stage study.
Last September, Calgary, Alberta-based Resverlogix Corp said its investigational apabetalone did not meet the main pivotal study goal of reducing major adverse cardiovascular events (MACE) — defined as cardiovascular death, non-fatal myocardial infarction, and stroke — when added to standard care in patients with type II diabetes, recent acute coronary syndrome, and low HDL cholesterol.
Apabetalone is a selective inhibitor of the BET family of proteins that play a role in the regulation of cell growth, differentiation, and inflammation. BET inhibition is an epigenetic mechanism — and the drug is designed to restore biological functions, altered by serious illnesses, back to a healthy state.
If DNA is the hardware, epigenetics is the software. DNA contains the code that dictates what cells do — while epigenetic changes modulate the effect of those messages, like a dimmer switch telling cells which proteins to make more of and where to limit protein production.
Detailed data from the 2,425-patient, placebo-controlled Phase III trial — dubbed BETonMACE — were disclosed in November. The results showed the MACE findings on the apabetalone arm were 10.3%, while the placebo patients chalked up 12.4% (p = 0.11). All other secondary goals, apart from stroke, favored the drug but did not induce a statistically significant effect.
Kausik Ray, the BETonMACE study chair and professor of public health and consultant cardiologist at Imperial College London, suggested that while apabetalone was not found superior to placebo — the drug “only just missed statistical significance” and it appeared that the trial was “a bit underpowered to show a benefit due to lower than expected event rates.”
“Given the promising signs…we think this (drug) holds considerable promise, and perhaps a slightly larger study with a few more events would allow us to assess more robustly whether this drug will provide a 20% treatment effect in this patient population,” he said in an interview with the American Heart Association.
As for Resverlogix, it is convinced the experimental therapy works. On its website the company says:
“From data collected in our clinical trials, we now know that apabetalone – through its effects on epigenetics – benefits multiple processes which contribute to the onset and worsening of disease. This is consistent with observed reductions in major adverse cardiac events (MACE) in study participants. Patients who take apabetalone have fewer heart attacks, strokes, and cardiac-related deaths.”
On Monday, the FDA granted the drug breakthrough status in combination with standard care for the secondary prevention of major adverse cardiac events in patients with type II diabetes mellitus and recent acute coronary syndrome.
Heart disease — the leading killer in developed nations (although cancer is catching up) — is a lucrative battleground for drugmakers big and small, although the field is littered with failure.
Resverlogix is also testing apabetalone in patients with Fabry disease.