Over the weekend, business website Bloomberg wrote a nice article called The Coming Wave of New Cancer-Fighting Drugs, highlighting the paradigm shift we’re seeing in oncology towards non-chemo treatments.
Bloomberg believes the “hottest area” in cancer drugs right now is immunotherapy, which has study drugs in clinical trial in every major type of cancer. The article reports that 25-30% of current experimental cancer drugs are immunotherapies. Earlier in 2014, several other authors also reported similar proclamations, including Elizabeth Cooney’s article for Harvard Medical School.
The fundamental goal of immunotherapy is to train a patient’s own immune system to attack cancer. Some “off the shelf” immunotherapies use generalized techniques to elevate immune responses to specific types of cancers in any patient, using common antigens and markers. Autologous immunotherapies use samples of a specific patient’s tumor to create a patient-specific treatment.
Most immunotherapies are created by sensitizing or enhancing immune system cells, such as dendritic or natural killer (NK) cells, which are injected into the patient like a flu shot. Other immunotherapies are given intravenously as monoclonal antibodies. Typically, immunotherapies have very low grade adverse side-effects compared to traditional chemo, while providing better efficacy than traditional chemotherapy. UCLA researcher Dr. Antoni Ribas noted when Merck’s Keytruda (pembrolizumab) was approved in September, 2014, that “Ninety percent of patients have basically no side effects.”
For deadly cancers like glioblastoma (the most common type of brain cancer) which typically are treated with toxic and largely unsuccessful monotherapy chemo regimens, the promise of immunotherapies should improve patient outcomes dramatically. Patients with unresectable tumors should also benefit from this new class of treatment. Many immunotherapies are proving to be synergistic with chemotherapy drugs, opening up the door to less toxic, multi-drug treatment regimens.
Bloomberg points out that many experimental immunotherapy drug companies are making significant progress towards FDA approval and should be expected in 2015 or 2016. Kite Pharma Inc., Juno Therapeutics Inc. and Bluebird Bio Inc. are all working on immunotherapies for blood cancers, and all expect to file approval applications within this timeframe. Bristol-Myers Squibb and Merck hope to have approval of lung cancer immunotherapies in 2015, in addition to their recent approvals of melanoma immunotherapies. Bristol-Myers Suibb’s Opdivo (nivolumab) was just approved in December, 2014 against melanoma, following the approval of Merck’s Keytruda by just 3 months. Both immunotherapies are PD-1 checkpoint inhibitors which block a key mechanism cancer cells frequently use to downregulate T-cell activity. Bristol-Myers Suibb also has an older melanoma immunotherapy on the market approved in 2011, called Yervoy (ipilimumab), which works by increasing the ability of cytotoxic T lymphocytes (CTLs) to find and destroy cancer cells.
Pfizer, AstraZenceca, and Roche all have similar immunotherapies in active development against cancer. All of these immunotherapies get to patients with initial approval for a single type of cancer, but many of them are believed to work in a wide variety of cancers. Merck, for example, is testing checkpoint inhibitors in more than 30 cancer types.
In glioblastoma alone there are at least 5 immunotherapies in clinical trial today, and the Oncophage heat-shock protein immunotherapy is already approved in some countries. The DCVax-Brain and CDX-110 immunotherpies have produced almost 3x survival advantages in clinical trials compared to current standard chemo treatments, respectively.
The first cancer immunotherapy approved in most Western countries was Provenge, a prostate cancer immunotherapy developed by Dendreon. It was approved by the US FDA in 2010. Pricing and forecasting missteps caused Dendreon to file for Chapter 11 bankruptcy 2 months ago, in November 2014. Dendreon plans to reorganize and continues to provide Provenge to patients. Many other immunotherapies in late-stage clinical trial are sometimes available in specific patient cases on a compassionate use basis.