FARA's Grass-Roots R&D

As with many compounds with an orphan designation, idebenone was originally in development for a much larger disease (Huntington's) and, after failing, was left on the shelf. (Takeda tried, without much success, to market it over the counter as an anti-aging treatment.) The compound moved swiftly into clinical trials: With toxicology and pharmacokinetics studies already completed, much was known about dosing and safety; with a database of hundreds of FA patients eager to have at it, enrollment wasn't an issue. NIH's Spinella stepped in, launching the first study in patients on the agency's own campus. FARA then raised the money to pay for Phase II trials. When idebenone showed modest efficacy at slowing down cardiovascular degeneration, the Swiss firm Santhera Pharmaceuticals took notice, licensing it from Takeda and launching a Phase III trial. Canada gave the drug conditional approval last July, and if FDA follows suit, Santhera will begin marketing Catena, the first FA drug, next year. But that's a big "if": data from the US trial did not show statistical significance, so the drug's fate depends on results from the longer and bigger EU study.

In its first foray into venture philanthropy, FARA awarded Edison Pharmaceuticals, a startup biotech, a $3.4 million research grant followed by an investment of $1.1 million to advance its lead product, alpha-tocopherol quinone (A0001), a coenzyme Q10 analog. In the lab, A0001 is able to stop the destruction of mitochondria, the energy source of cells that is believed by most researchers to be the cause of FA's neurodegeneration. With NIH backing, the group joined with Edison and a leading researcher to conduct Phase I studies. New York–based Penwest licensed this star in FA's clinical pipeline and is running Phase IIb trials.

Excited by Scripps Institute research showing that a compound that blocks the Histone Deacetylase (HDAC) enzyme was able to target FA's mutant gene and turn up its frataxin-producing capability, FARA paid for efforts to design the most effective HDAC inhibitor, using its own cell lines for the tests. "This is our one near-term shot at getting inside the gene and increasing its productivity," he says. "If it works as well in patients as does in our mouse models, it could be profoundly therapeutic." With backing from FARA and the Muscular Dystrophy Association, Boston biotech RepliGen is refining the HDAC inhibitor further for a planned IND filing later this year.

Investing in drug development is, for FARA, little different from lending a drugmaker its patient registry, transitional tools, or other resources. "We may get a small percentage of market proceeds if a company gets to that point," says Bartek, "but we're in this for the drugs, not the money."

But the foundation has not completely abandoned advocacy's tradition of confrontation. When Santhera set the price of high-dose Catena in Canada at $100,000 a year, Bartek was furious, not least because FARA had done considerable heavy lifting for the drug. "We did the basic science and a lot of the clinical research," he says. "Santhera didn't have to invest a dime in anything but a six-month, 340-patient Phase III trial—using our own patients, doctors, and sites. Now some patients in Canada are reporting that their government insurance may fall short. "We have to make sure they can't turn around and price-gouge our patients," he says.