In previous notes, I discussed companion diagnostics (see for example: More Details About Roche's Companion Diagnostics Strategy; A Closer Look at Companion Diagnostics Strategies; Some Interesting Insights into Companion Diagnostics; Companion Diagnostics Gains Wider Acceptance in FDA Despite Challenges). These are lab tests for patients, usually with cancer, to determine which drugs will be most effective in treating their disease. The underlying idea is that the lab test determines whether the patient's cancerous cells harbor the genetic error that a particular drug has been designed to exploit. Hold this thought.
Immunotherapy is the newest and most effective way to treat malignant melanoma (see: The Latest Research On Using The Body’s Own Immune System To Fight Cancer). This therapeutic approach has been designed to unleash the patient's own immune system in an attack on the malignant cells. A recent article about immunotherapy for melanoma cited the importance of a companion diagnostics in treating some cancer patients (see: New System for Treating Cancer Seen as Hopeful), Below is an excerpt from it:
One of the immune drugs, Yervoy, which was approved for use against melanoma in 2011, allows for a two-year survival rate [in melanoma patients of about 25 percent when used alone....The other drug, nivolumab, which is still experimental, had a two-year survival rate above 40 percent when used alone in a study. The drugs block the actions of proteins that act as brakes on the immune system, preventing them from attacking the tumors. Yervoy, also known as ipilimumab, releases the brake known as CTLA-4. But the main interest is in nivolumab and similar drugs coming from Merck, Roche and AstraZeneca that release a brake called PD-1....[T]here were signs [at the recent ASCO conference] that the drugs that block the action of PD-1 might also work for bladder cancer, head and neck cancer, and ovarian cancer. In a small study, Roche’s drug, known as MPDL3280A, shrank tumors in 43 percent of a subset of patients with advanced bladder cancer. The company might now make bladder cancer the priority for its first approval rather than lung cancer....The subset consisted of patients whose tumors produced a protein called PD-L1, which binds to PD-1 on immune system cells and then shuts down those cells. Companies are exploring whether a PD-L1 test can be used to determine which patients should get the drugs. That would be important because the drugs are expected to cost at least $100,000 a year.
CTLA-4 is found on the surface of T lymphocytes and is a protein receptor that down-regulates the immune system. Yervoy serves to release that brake, thus enabling the patient's T cells to kill the cancer cells. Blocking the action of PD-LI also releases the brakes on the patient's immune system. This therapeutic approach is also referred to as checkpoint inhibitors. Releasing the brake is a very apt metaphor for describing the action of some of these immunotherapy drugs. Here's a much broader list of the functions of companion diagnostic tests, an indication of the growing sophistication of this field (see: Companion Diagnostics):
Companion diagnostics can:
- Identify patients who are most likely to benefit from a particular therapeutic product
- Identify patients likely to be at increased risk for serious side effects as a result of treatment with a particular therapeutic product
- Monitor response to treatment with a particular therapeutic product for the purpose of adjusting treatment to achieve improved safety or effectiveness
On July 31, 2014, the FDA issued Guidance for Industry: In Vitro Companion Diagnostic Devices to help companies identify the need for companion diagnostics at an earlier stage in the drug development process and to plan for co-development of the drug and companion diagnostic test. The ultimate goal of the guidance is to stimulate early collaborations that will result in faster access to promising new treatments for patients living with serious and life-threatening diseases.