Get most biotech executives talking about the FDA, and they usually tiptoe around with diplomatic sound bites, or maybe they’ll grumble about what they consider unreasonable burdens and arbitrary decisions by the U.S. drug regulatory agency.
The guys at Menlo Park, CA-based Optivia Biotechnology have a completely different take.
“The tougher the FDA gets, the better our business gets,” says Peter Milner, Optivia’s co-founder and executive vice president of corporate development.
Optivia, a company started four years ago with only about $500,000 in seed capital to date, has grown from one man’s idea in a garage into a profitable company with about 30 employees and a roster of 50 customers from Big Pharma, biotech, and academic research labs. Optivia has grown up based on a proprietary lab test that looks at transporter proteins that shuttle drugs, nutrients, and other substances in and out of cells. The field of research was pretty obscure when CEO Yong Huang got the company started in his garage (literally), but it has encountered some good fortune over the past year as the FDA has become increasingly vigilant in asking drugmakers to study the effect their compounds have on certain transporter proteins.
The FDA is particularly interested in how these transporters can be involved in drug-drug interactions, which can lead to dangerous side effects that sometimes only appear after a treatment has been taken by thousands or millions of people, on the market. Biologists say there are about 300 to 400 of these transporters that act as cellular gatekeepers. The FDA is trying to learn more about them, to avoid new cases like the debacle with Bayer’s cholesterol-lowering drug cerivastatin (Baycol). That drug was withdrawn from the market after reports of a fatal muscle disorder were discovered in patients who got the drug along with another compound known as gemfibrozil—through what was determined to be a bad transporter reaction.
Drug regulators have long required companies to run tests that shown how their drugs get metabolized, or washed out of the body, usually through certain enzyme pathways in the liver. Doctors and pharmacists use that information to make sure they don’t prescribe too many different drugs that get metabolized through the same pathway, which could create a traffic jam of sorts, causing too much of the drug to remain in the bloodstream or tissues for too long. Transporter proteins also play an important role in drug metabolism, but the FDA has only recently begun to step up its requests for lab studies about them. That’s because transporters are complex protein structures that have been harder to study than enzymes, Huang says.
The FDA has singled out transporter biology as one area of research that could help improve the drug development process, as Janet Woodcock, a senior FDA official, described in this review article in Nature a year ago. Optivia isn’t the only company running tests of drug-drug interactions for drugmakers on transporters—Solvo Biotechnology and BD Biosciences are a couple of competitors. But Optivia has clearly made a lot of inroads in the market, particularly since the FDA has become more public about its desire for transporter studies. Optivia has signed up about one-third of the world’s Big Pharma companies as clients (including GlaxoSmithKline and AstraZeneca). Optivia has also secured a collaboration with the FDA, and formed a research partnership earlier this year with UC San Francisco. The UCSF collaboration has the ambitious goal of testing 2,000 prescription drugs against key transporters in the liver and kidneys. It’s the most comprehensive study ever to look at prescription drugs and their effect on transporters, according to Kathleen Giacomini, a professor and co-chair of the UCSF Department of Bioengineering and Therapeutic Sciences.
The business is set up so drugmakers pay fees to have Optivia test their compounds for drug-drug interactions in a petri dish. It’s really just one small step of many in the overall drug development process, but companies have learned that even small oversights can delay new drug applications, costing them millions down the road. At least three customers have told Optivia that the FDA is turning up the heat, by asking drug applicants to supply data on transporter drug-drug interactions in their new drug applications, says Carole Melis, a spokesperson for the company.
Fee-for-service businesses tend to have limited growth potential, and Huang wanted to stress that he doesn’t see the company being limited to this kind of work. Drug-drug interactions are the “tip of the iceberg with transporter biology. We’re a transporter biology platform,” he says.
What that means is Optivia wants to find ways to generate much more value out of its knowledge of transporters—by identifying some of them as new targets for drug development. For example, there are diabetes drugs in development now from AstraZeneca and Bristol-Myers Squibb that take aim at SGLT-2, a transporter in the kidney. If those oral pills live up to their billing, they should be able to help diabetics to flush excess amounts of sugar out of their systems through the urine. Anyone who can find more biological targets like that could obviously be sitting on something pretty valuable to major drugmakers.
“Drug-drug interactions are only part of the story,” Huang says. “It’s about utilizing transporter biology to discover more and better drugs.”