By Turna Ray
A new personalized medicine partnership between Sanofi-aventis and Scripps Genomic Medicine will initially focus on using pharmacogenomics to individualize treatments for common diseases affecting metabolism and aging.
Under the terms of the collaboration announced last week, Sanofi will fund up to three projects per year that it will conduct in partnership with Scripps scientists.
"We are concentrating on two initial areas — diabetes and aging research," Eric Topol, chief academic officer of Scripps Health, told Pharmacogenomics Reporter this week. "Diabetes PGx work is of vital interest to Scripps, Sanofi, and the public."
Sanofi already has a presence in these disease settings. In the area of drugs to attenuate conditions related to aging, the company markets Actonel for osteoporosis, Hyalgan for osteoarthritis, and Arava, a disease-modifying anti-rheumatic drug. Diabetes treatments being marketed by Sanofi include Lantus, Apidra, Amaryl, as well as DiaBeta to improve glycemic control in type 2 diabetes patients.
As Scripps is researching potential areas to apply pharmacogenomics in Sanofi's pipeline, Sanofi in turn will have access to Scripps research programs that contribute to its priority areas. Sanofi will have non-exclusive rights to any research tools developed through the funded projects and will have preferred access to Scripps labs to conduct work to advance research-stage products through the pipeline.
Topol told PGx Reporter that the collaboration has been incubating for more than 20 years. In that time, the two entities have worked together on several clinical trials for the anti-platelet drug Plavix (clopidogrel), including the Clopidogrel versus Aspirin in Patients at Risk of Ischemic Events trial, or CAPRIE; Clopidogrel for the Reduction of Events During Observation trial, or CREDO; and the Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management and Avoidance trial, or CHARISMA.
Earlier this year, the US Food and Drug Administration placed a black box warning on the label for Plavix, which is marketed by Sanofi and Bristol-Myers Squibb, to recommend genetic testing ahead of administration of the treatment to ensure that patients don't harbor SNPs that reduce their ability to respond to the drug.
In addition to conducting studies on Plavix with Sanofi, Topol was an early adopter of PGx testing to dose Plavix at Scripps Green Hospital in San Diego.
The announcement of the partnership follows on the heels of news that an investigational weight loss drug at Sanofi that failed clinical trials could have been resuscitated by pharmacogenomics.
Specifically, a study led by Topol on a Sanofi weight loss drug, called rimonabant, had to be prematurely terminated due to "serious neuropsychiatric effects that [were] deemed unacceptable by regulatory authorities." Following the publication of the study in The Lancet Aug. 14, Topol said that genomics may have saved rimonabant from failure.
Topol and colleagues were investigating rimonabant in a randomized, placebo-controlled trial to see if it could improve cardiovascular outcomes in patients — 18,695 patients were randomly assigned to receive either rimonabant or placebo — but Sanofi stopped the trial, called Rimonabant for Prevention of Cardiovascular Events, or CRESCENDO, upon the recommendation of the US Food and Drug Administration after four patients in the trial receiving rimonabant committed suicide.
Rimonabant has a history of difficulty with regulatory authorities. Sanofi pulled its marketing submission for the drug with the FDA in 2007 after an advisory committee gave it a negative review, citing concerns that the drug caused increased risk of suicide and depression. A year later, rimonabant was taken off the European market.
A spokesperson for the FDA would not comment on whether rimonabant would be a good candidate for its Voluntary Exploratory Data Submissions program, which is a program through which agency officials provide pre-submission guidance to companies on potential personalized medicine products.
The FDA launched the VXDS program several years ago to encourage sponsors to share genomics data with the agency without any regulatory repercussions. According to agency officials, since 2008, submissions to the VXDS program have grown 250 percent.
Drug developers are starting to use the program to bring back failed drugs with the help of genomics strategies. For example, last year Novartis submitted data to VXDS for lumiracoxib, a COX-2 inhibitor that the FDA rejected in 2007 due to serious liver adverse events. After discussions with agency officials, Novartis has settled on a genetic marker with which the company plans to resubmit the drug with a companion diagnostic.
Resuscitating rimonabant with PGx to avoid neuropsychiatric adverse events may have its own unique challenges. At this point, there haven't been any drugs for which PGx strategies have been successfully applied to avoid neuropsychological problems.
According to Topol, the failed weight loss drug was not the catalyst for the Scripps/Sanofi personalized medicine pact. However, he seems to think that rimonabant could have had a shot if Sanofi had pursued PGx studies to identify a subpopulation in which the drug did not cause suicidal thoughts.
"If we had the DNA samples from approximately 50 individuals who took rimonabant and had suicidal gestures, ideation, or had committed suicide, there is at least a reasonable chance, given the parallel work in areas such as lumaricoxib (liver toxicity) and interferon for hepatitis C (efficacy), that we could have come up with a genomic underpinning for this side effect," Topol said in an e-mail.
"It is clear that neuropsychiatric side effects have not yet come from genome-wide association studies, but only recently have we been seeing the powerful signals that can be identified with relatively small numbers of patients affected," he added.
Sanofi did not respond to e-mailed questions pertaining to its collaboration with Scripps.