Testing Experimental Drugs in Combination – A New Trend
Sanofi-Aventis and Merck KGaA announced recently they are teaming up to test new cancer drugs in combination, joining a growing trend among drug makers to combine different cancer therapies in early-stage clinical studies.
Combinations of different drugs are used frequently in the treatment of cancer, but such regimens are normally developed only after medicines reach late-stage testing or are already on the market.
Now that is starting to change.
Some experts believe such combinations of experimental-stage drugs could in the future become commonplace as researchers hunt for better “targeted” treatments to disrupt the multiple signaling pathways that are used by cancer cells to proliferate and grow.
Companies have undertaken innovative strategies to study these drugs in combination. In June 2009, AstraZeneca and Merck & Co. entered into an agreement to conduct joint early stage clinical trials of their respective cancer drugs – AstraZeneca’s MEK inhibitor and Merck’s AKT inhibitor.
“There is strong scientific rationale to suggest that the potential benefit of this combination to cancer patients may exceed the sum of the parts,” AstraZeneca said in a press release describing the partnership with Merck & Co.
This latest collaboration involves the experimental MEK inhibitor from Merck KGaA and two investigational agents from Sanofi-Aventis, SAR245408 and SAR245409, which are both inhibitors of the PI3K/mTOR pathway and obtained through Sanofi’s partnership with Exelixis.
In the current collaboration, each company will be responsible for conducting an initial Phase I study. Sanofi-Aventis will be granted a license to test Merck’s MEK inhibitor in combination with SAR245408, while Merck will assess its drug in combination with SAR245409.
There are some considerable clinical and regulatory hurdles to developing two drugs in combination. Recently, however, the FDA has taken a significant step to encourage companies to work together . . . or at least consider the possibility.
The FDA issued draft guidelines designed to encourage companies to work in tandem to develop two or more new drugs to be used in combination to treat cancer and infectious diseases, among other illnesses. In addressing the new guidelines, FDA commissioner Margaret Hamburg said they are the result of a growing understanding that experimental therapies may need to be used together in order to be more effective or to prevent drug resistance.
“We are not fully harnessing the promise of this science for the benefit of patients,” Hamburg told an audience recently. “We clearly need to act.”
Advocates for new treatments for cancer said they see the Agency’s proactive outreach as the first step to establishing a clear regulatory pathway for these combination therapies and a move that will spur more collaboration between companies to develop these novel combinations.
Despite the excitement, efforts to study investigational drugs in combination are still in their infancy. Phase I is the first stage of clinical testing, so these new drug “cocktails” are still several years from reaching the market. Scientific, clinical, regulatory and intellectual property hurdles all must all be overcome if these novel combinations are to provide breakthrough cancer therapies for the patients who desperately need them.
One thing is for certain – this new trend is likely here to stay.