Marking another promising advance for the treatment of patients with chronic lymphocytic leukemia, including those with a rare subset of this blood cancer, the U.S. Food and Drug Administration (FDA) has granted priority review for an investigational compound that has shown positive results in a Phase II clinical trial.
Venetoclax has shown great potential as a new way of treating CLL patients who have received at least one prior therapy. It also appears to be effective for patients with a rare subset in which a piece of chromosome 17 is missing. Venetoclax works by inhibiting the BCL-2 protein and enabling a signaling system that tells cells, including cancer cells, to self-destruct.
More than 126,000 patients in the U.S. currently live with CLL, a typically slow-moving blood cancer that begins in the bone marrow. Of those CLL patients who do not respond to therapy, or who have relapsed, approximately 30 percent are found to have a mutation in which they are missing part of chromosome 17.
A Priority Review designation is granted to medicines that the FDA believes have the potential to provide significant improvement in the treatment, prevention or diagnosis of a disease. The compound was granted a Breakthrough Therapy Designation in April 2015 in order to expedite its development and review.
The Leukemia & Lymphoma Society (LLS) has supported research advancing this therapy since 2002. The work is being led by Jerry Adams, Ph.D., at Walter & Eliza Hall Institute of Medical Research in Melbourne, Australia, through a Specialized Center of Research (SCOR) grant. Adam’s group has been funded by three SCOR awards ($6.25 million over each five-year period), the largest grants in the LLS portfolio designed to encourage ground-breaking collaborative research leading to new therapies.
Results presented at last month’s American Society of Hematology (ASH) Annual Meeting showed that a statistically significant percentage of patients in the Phase 2 clinical trial responded to the therapy.
Data included 107 patients with relapsed or refractory disease, all but one of whom had 17p deletion. The study met its primary endpoint, with 79.4 percent of patients showing an overall response rate. In addition, 7.5 percent of patients achieved a complete response with or without complete recovery of blood counts in the bone marrow.
Of 45 patients who were tested for minimal residual disease in the blood, 18 had no cancer detected. Ten of these 18 patients also had bone marrow tests and six had no cancer detected. At one year, 84.7 percent of all responses and 94.4 percent of the responses of those patients who were tested for minimal residual disease were maintained. The one-year progression-free survival and overall survival rates were 72 percent and 86.7 percent, respectively.
The possibility of a new drug approval for patients with a poor prognosis is the latest encouraging news for patients with CLL. In just the past two years there has been an explosion of new treatment options for CLL patients, including targeted therapies such as ibrutinib, idelalisib, obinutuzumab and the still experimental CAR-T immunotherapy, most of which have been supported by LLS funding.