The Next Big Thing: Targeted Treatments

Personalized medicine involves using the advanced tools of molecular genetics and diagnostics to predict how patients will respond to drugs, reducing harmful side effects and increasing benefit. In addition, the panoply of technologies enabling this revolution in medicine can produce a personal medical profile that can guide the physician toward selecting the most appropriate drug or treatment regimen and help individuals stave off diseases before they manifest themselves. This dual combination of diagnostic and treatment technologies is at the heart of personalized medicine and is poised to transform healthcare dramatically.

The science that will make personalized medicine a reality is evolving at a rapid pace. Biomarkers have already had a significant impact on oncology and infectious disease markets, leading to targeted therapies. Uncovering the genetic differences that determine how a person responds to a drug, and developing tests, or biomarkers, for those differences, will become the key to future patient care as well as help reduce waste we have in the healthcare system today.

The potential of personalized medicine has also caught the eye of investors. According to a number of surveys, in 2008 nearly $500 million was invested into companies involved in developing innovative diagnostic tests. Also, to bring a new biomarker-based diagnostic test to market takes about four to five years and around $70 million, making investments less costly and risky than betting on a pre-clinical stage drug candidate.

Benefitting from this new investor sentiment are companies like Precision Therapeutics, Crescendo Bioscience, Neuroptix and Pathwork Diagnostics. Pittsburgh-based Precision, which is creating tests that predict patients’ response to drugs, secured $43 million in funding to advance the development and commercialization of its ChemoFx diagnostic test that helps physicians select the most effective chemotherapeutic regimen for cancer patients. Using ChemoFx to help select treatment can lead to better clinical outcomes while reducing exposure to toxic, ineffective chemotherapeutic agents. Clinical trials have demonstrated the potential for 1.4-times longer overall survival and a two- to three-fold improvement in progression-free cancer survival when ChemoFx is used in advance of making a therapeutic choice.

“Precision Therapeutics is a great example of the type of diagnostic company we will invest in,” says David Hirsch, a principal at Longitude Capital, a venture capital firm that invests in medical device and biotechnology companies. Longitude Capital was the new lead investor in the venture round.

South San Francisco-based Crescendo Bioscience, which received a $20 million investment, is developing a broad range of diagnostic tools to help rheumatologists better manage patients with autoimmune and inflammatory diseases. The company is initially focused on rheumatoid arthritis, which affects more than 1.5 million patients in the United States and more than 3 million in Europe. Current diagnostic tools for assessing the status of rheumatoid arthritis sufferers are largely subjective, imprecise and cumbersome to administer in daily practice. Although there is no known cure, there are many drugs that vary in effectiveness and adverse reactions from patient to patient. Finding the ideal regimen for a patient represents a tremendous challenge for these doctors.

Other financings include Acton, Mass.-based Neuroptix, which completed an $18.5 million Series B investment round last year to further develop its diagnostic platform for Alzheimer’s disease. The platform is based on a promising biomarker for the detection of beta amyloid proteins responsible for the formation of plaques in the brains of patients developing the neurodegenerative disease.

And Redwood City, Calif.-based Pathwork Diagnostics attracted $20 million in venture funding on the strength of receiving approval from the U.S. Food and Drug Administration for its Pathwork Tissue of Origin Test for use in determining the origin of uncertain tumors. The test analyzes a tumor’s gene expression pattern to help pinpoint the source of hard-to-identify tumors and is the first test of its kind to receive FDA clearance.

In addition to companies developing molecular diagnostics, the future of personalized medicine will be driven by pharmacogenomics — the marriage of pharmacology and genetic testing. Gene-based tests lend themselves to the “combination product” brand of personalized medicine where a test is paired to a therapeutic to determine whether it is appropriate to use. The poster child for genomic personalized medicine is Genentech’s Herceptin (trastuzumab). As a pre-condition for receiving Herceptin, patients must undergo a test to measure a gene that confers a tumor’s susceptibility to the drug. This business opportunity will evolve as more drugs are approved with companion diagnostics.

Amgen’s colon cancer drug Vectibix (panitumumab) won approval in Europe because the company was able to demonstrate it could narrow the patient population using a Manchester, U.K.’s company’s diagnostics assay to identify those patients with a certain genetic mutation that made them resistant to the drug. Taking these nonresponders out of the treatment pool brought the response rate up to a high enough level to win approval.

Companies are beginning to see a competitive advantage to linking tests with new drugs. Pfizer’s Selzentry (maraviroc), a CCR5 antagonist for the treatment of HIV infection, gained FDA approval in 2007 on the strength of Monogram Biosciences’ diagnostic test, which identifies the CCR5 tropism in order to narrow the list of patients to those who could be helped by treatment.

“Every molecule companies are developing now has a biomarker strategy,” says Larry Lesko, director of the Office of Clinical Pharmacology and Biopharmaceuticals at the FDA. “The challenge is identifying the marker that will do the job.”

The pharmaceutical industry once rooted in “blockbusterology,” is not only “walking the walk” but now “talking the talk” about personalized medicine. Eli Lilly President and CEO John Lechleiter has affirmed that his company’s business model will accommodate personalized medicine. And Switzerland’s Roche paid over $3 billion for Tucson, Ariz.-based Ventana Medical Systems, a leading supplier of automated diagnostic systems to the anatomical pathology market, to give it a greater footprint in the personalized medicine world.

“The pace of adoption of personalized medicine is accelerating in such a way that it proves that we are past that tipping point,” says Carol Kovac, venture partner at Burrill & Company and co-chair of the 5th Annual Burrill Personalized Medicine meeting, which was held in November 2009. “Eight years ago when the first draft of the genome was announced, you could argue that personalized medicine was still — maybe not a dream — but a future vision. But today, we see real companies in the marketplace with real solutions.”

Kovac says personalization of therapies is not only becoming more widespread, but emerging as a best practice and a standard of care in some areas. She expects that will only increase, especially as more and more proof points come into the market.

“We are in a very rapidly accelerating phase of adoption of practical solutions in personalized medicine,” she says. “There will be road blocks along the way that could derail the momentum that has been building around personalized medicine — the most notable of which is reimbursement of genetic testing and pharmacogenomic tests. But these will be quickly addressed as coming to grips with the spiraling costs of healthcare is high on the nation’s agenda. Personalized medicine will certainly be part of the solution.”