Regulatory hurdles, along with dosing problems, have come to plague a new class of cancer drugs that showed highly encouraging results in early research. Those obstacles have frustrated breast and ovarian cancer patients who are carriers of cancer-causing mutations, particularly prevalent among Ashkenazi Jews, and for whom it was hoped the medicines would prove especially helpful.
Last December, patients eagerly anticipating the completion of trials and FDA approval of Olaparib — then the farthest along in research involving a novel class of therapies called “PARP inhibitors” — were dealt a blow when maker AstraZeneca announced it was, for the time being, discontinuing its late-stage Phase III trial of the drug on patients with serous ovarian cancer, the most common form.
The pharmaceutical company said that Olaparib’s previously reported impressive ability to halt progression of the disease for a time, with limited side effects, would not likely translate into “overall survival benefit,” or the length of time patients live after starting the drug.
No PARP inhibitors are currently in large-scale Phase III trials — the last stage of testing before a company can win FDA approval. But multiple Phase I and II trials are underway. Some early trials indicated that the drugs might prove particularly effective in patients with the inherited BRCA1 or BRCA2 genetic mutations involved in 5% to 10% of all breast and ovarian cancers. With about a one-in-40 chance of carrying a BRCA mutation, Ashkenazi Jews are at higher risk for those diseases compared with those in the general population, where about one in 500 carry a BRCA mutation.
Some academics view the delays in PARP trials as reflective of a contentious change in regulatory policy, regarding how new drugs are evaluated. Dr. Mary Daly, who chairs the department of clinical genetics at Fox Chase Cancer Center in Philadelphia, said: “The move is to thinking that it is not enough to put off progression with a drug, but that the drug has to actually extend life. It’s still somewhat controversial, because some argue that prolonging progression-free survival is valuable in itself.”
Olaparib researchers also reported difficulty in identifying a suitable tablet dose for use in a Phase III trial. AstraZeneca is currently reformulating Olaparib into higher-dose capsules, but the process may significantly delay completion of the clinical trial.
Other PARP inhibitors face similar problems.