Scientists have identified 7,000 monogenic diseases, those caused by a single mutation in a specific gene and better known as orphan diseases. But only a few hundred such illnesses have an approved therapy, Jim Geraghty, JD, MS, explains.
Geraghty has spent his career launching companies with missions to overcome the hurdles of developing treatments for people with rare but serious diseases. As a seasoned biotech executive and author of the book Inside the Orphan Drug Revolution: The Promise of Patient-Centered Biotechnology, he addressed the biggest challenge scientists face in the next generation of diseases: “We must find a way to leverage scientific and medical learnings so they are shared more broadly across related patient populations."
His business expertise spans 30 years as a biotech strategist and executive, including acting as the righthand man to Henri Termeer, MBA, the founder of the biotech company Genzyme. Genzyme, now a subsidiary of Sanofi, has developed several groundbreaking treatments, including enzyme replacement therapies (ERTs) for Gaucher disease, Fabry disease, and Pompe disease, all orphan diseases.
Stories to inspire a new generation of entrepreneurs and physician-scientists
After reading the biography of Termeer, Geraghty decided to tell the broader story of the orphan drug industry, which began in the United States with the passage of the Orphan Drug Act in 1983. Drugs for rare diseases had been “orphaned” by the pharmaceutical industry as it increased focus on short-term profits.
“It abandoned taking on really difficult and life-threatening diseases because some of the populations were too small,” Geraghty explained. The Act, sponsored and driven by family activists who cared about their children, sparked a revolution by entrepreneurs and physician-scientists worldwide to treat and develop therapies for patients with rare diseases.
Geraghty said his book is meant to inspire another generation of entrepreneurs and physician-scientists. It tells the story of Abbey Meyers, the founder of the National Organization for Rare Disorders (NORD). Her activism in searching for a treatment for her son’s Tourette’s Syndrome led to the passage of the Act.
Geraghty also includes the story of Roscoe Brady, MD, a well-known investigator at the National Institutes of Health studying Gaucher Disease, a rare genetic disorder that affects the body's ability to break down a certain type of fat molecule called glucocerebroside. Brady, with the help of the founders of Genzyme, gathered thousands of human placentas to extract cells based on the hypothesis that their mesenchymal stem cells could help replace the deficient enzyme and reduce the buildup of glucocerebroside. This experimental treatment led to a trial with seven patients. Six didn’t respond, but the seventh miraculously recovered.
“Many people said it was a fluke and failed trial,” Geraghty explained. “But people who met the patient and understood what had happened persevered until Genzyme developed its first drug whose success paved the way for the orphan drug revolution.”
The need for policy solutions
Geraghty explained the current drought in investment in biotechnologies for rare disease therapies, pointing to organized interests in the insurance industry and those lobbying the US Congress to cap drug prices without recognizing the impact that will have on innovation.
“If we take the orphan drug revolution for granted, it is at risk,” he said. “We must continue to maintain reimbursement at a level that supports investment in innovative therapies for the future.” He also pointed to accelerating drug approval and the importance of newborn screening and early diagnostics.
Advice to biotech startups
It takes a tremendous sense of mission for a rare disease company to achieve success. “Temeer was an economist, and he understood that to be sustainable, a company had to be connected to bringing therapies directly to patients and securing reimbursement from payers,” Geraghty said.
The leaders of Genzyme learned that to build a company that will be independently sustainable for the long term, that company has to have control of some of its products. It could license out to others, but it had to retain control of the financial return to investors,” Geraghty noted.
But most importantly, he emphasized that no one should launch a company unless they feel it’s something they have to do. “It is crazy, and it's going to be incredibly difficult, and most things you try will fail,” he said. “No company has ever been successful based on the thesis it set out in its original investment documents. Success comes because they believed in the mission.”
