By: Richard Pazdur, M.D. and Gideon Blumenthal, M.D.
Last week, we approved a new drug for patients with a certain type of late stage, non-small cell lung cancer (NSCLC).
It’s one of four targeted therapies for lung cancer that have been approved since 2011—therapies that are the result of a new and forward-thinking approach to understanding the disease and its causes.
Within the last decade, the high quality of the data in the applications submitted to the agency and our collective understanding of the genetic and molecular underpinnings of lung cancer have enabled us to move from classifying the disease by what can be seen under a microscope, to looking at the patient’s molecular profile and classifying and treating the cancer by specific subtype. Scientists can now identify “driver oncogenes,” which cause a normal cell to become cancerous and promote the growth of a patient’s tumor. They can develop targeted therapies aimed at shutting down these aberrant genes and pathways, an example of an approach called personalized medicine.
Last week’s approval of Zykadia (certinib) provides a new treatment option for patients who comprise a relatively small subset of lung cancer and previously had few treatment options. While about 85 percent of lung cancers are NSCLC, making it the most common type, only about 5 percent of patients’ tumors are anaplastic lymphoma kinase (ALK) positive. Zykadia blocks this ALK protein that promotes the development of cancerous cells. In a clinical trial of 163 patients with metastatic ALK-positive NSCLC who had progressed on or were intolerant to a similar drug, results showed that tumors shrank in about half of the participants, and this effect lasted an average of seven months.
Moreover, the approval process exemplifies the important role of FDA and the strength of the collaborative process between FDA, industry, health advocacy organizations and other stakeholders. And it illustrates the dedication and enthusiasm of FDA reviewers who carefully, but expeditiously, analyzed complex study results to allow for earlier approval to support patient access to this new drug.
FDA granted breakthrough designation to this drug, thereby streamlining the development and review process with an “all hands on deck” approach. In fact, due to the enhanced understanding of ALK in lung cancer and the frequent interactions between the FDA and the commercial sponsor, it took less than four years—versus the roughly ten years it used to take—from the initial study of a drug to FDA approval.
We hope to further extend the collaborative effort in the future by participating in the use of the master protocol process. In a master protocol, multiple drugs and biomarkers can be tested in in a single, ongoing clinical trial. Under this approach, based on individual patient profiles, researchers can randomly assign patients either to one of several targeted treatments or to a control regimen of standard chemotherapy. We believe this will enhance the efficiency of clinical trials and help deliver safe and effective therapies to a patient population where few such therapies exist. Stay tuned: we hope to say more about this process in a future FDA Voice blog.
Of course, the progress we are making can’t come fast enough. There are far too many cancer mutations with few or no therapies developed thus far to treat them. But we and our colleagues throughout the medical research world are continuing to look for new and creative approaches to treat the disease. We’re well on our way.
Richard Pazdur, M.D. is Director of the Office of Hematology and Oncology Products at FDA.
Gideon Blumenthal, M.D. is the Team Leader of Thoracic Oncology in the Center for Drug Evaluation and Research at FDA.