SMA Foundation Makes the Case for Research in Rare Disease

By Debbie Strickland

The errant gene has been isolated, the National Institutes of Health has made the disease a priority and now a young foundation is pitching biotech companies to develop a cure for spinal muscular atrophy, a disabling, often fatal genetic disorder that afflicts some 25,000 Americans.

Dinakar Singh and Loren Eng launched the Spinal Muscular Atrophy Foundation (SMAF) after their infant daughter Arya was diagnosed with the disease in 2001. Initially, the couple had planned simply to donate to existing patient and research groups, but they soon discovered there was a need for an entirely new kind of organization, one that applied business savvy to the problem of developing a cure.

And Singh and Eng had that savvy. Singh is a Goldman Sachs veteran and founder and CEO of a $2.8 billion hedge fund, TPG Axon, and Eng has investment banking experience and a Stanford M.B.A. They have built a board that comprises not only leading scientists and clinicians, but also federal advocacy experts, venture capitalists and biotech executives.

“Historically, a lot of organizations do a wonderful job of raising funds for academic researchers and a wonderful job of family support, but they are less focused on industry,” said Eng. “We wanted to make sure a drug got across the finish line.”

To that end, SMAF has developed a full business case to share with biotech companies, stressing that SMA is now “solvable”:

– It’s a single-gene (SM1), single protein disease. A backup gene, SMN2, which produces the protein at about 10 percent efficiency, offers a potential target for up-regulation. SMN2 productivity seems to be a factor in determining severity.
– Drug screening tools are available, including mouse models (distributed by Jackson Laboratory) and drug screens.
– High-throughput screening has identified potential compounds, including several that are already Food and Drug Administration-approved.
– A clinical trial infrastructure is in place, with several pilot trials under way.

Market size for this “common” rare disease is estimated at between $250 million and $750 million, which falls short of the “blockbuster” threshold of $1 billion. However, SMA is an orphan drug indication (triggering federal incentives, including extended market exclusivity) and can be marketed inexpensively to a small group of specialists.

“This is about economic common sense,” said Singh. “Even though it’s a smaller market, it could be a very lucrative market.”

SMA research and, possibly, therapies are likely to have spillover benefits in related diseases such as amyotrophic lateral sclerosis, Alzheimer’s disease and Huntington’s disease.

SMAF is not just providing companies with the bullet-point economic rationale for pursuing therapies, but has also jump-started work in the private sector by providing more than $7 million in grants to two biotech firms, Curis and CombinatoRx, with the goal of new compounds entering clinical testing as early as 2006–07.

“This really is a win-win,” said Alexis Borisy, president and CEO of CombinatoRx, a young Boston-based company that searches for novel combinations of approved drugs to treat disease. “The foundation is committed to finding a cure for the disease and understands the reality of what it takes. They pay 100 percent of research costs, and we keep the upside.”

Despite the progress that has been made in SMA and other degenerative neurological diseases, drug research in these areas is still considered “too high risk, too new,” with “no proven pathway” to approval, Borisy said. By providing valid assays, key intellectual property and funding, SMAF has made the field “very appealing.”

The foundation has funded academic researchers as well and is seeking additional alliances. Singh and Eng encourage those who are interested to contact the foundation (see www.smafoundation.org for detailed contact information).

NIH Investing $20 Million

Of course, a nonprofit “could never match what the federal government could throw at a disease if they were to focus on it,” said Eng. Early on, SMAF targeted funding at the NIH, where SMA funding lagged behind other genetic diseases (cystic fibrosis, for example, affects twice as many people, but receives nine times more funding).

Eng testified before Congress, her brother knocked on doors at the Capitol, and the foundation persuaded 49 scientists to sign a letter to NIH Director Elias Zerhouni seeking more funding.

As a result of the campaign, the agency in 2003 selected SMA for a $20 million pilot drug discovery and development project that aims to generate clinical drug candidates by 2007. According to the program announcement, “SMA is an ideal candidate for targeted therapeutics development.”

Debbie Strickland is BIO’s director of publications.