Rare disease: A difficult therapeutic path

Rare disease panelWhen a rare disease affects you or your family, it doesn’t seem rare. Add them all up, and rare diseases aren’t all that uncommon. What’s rare is for patients to receive effective treatments.

“There are 7,000 rare diseases, and under 400 approved drugs,” says Peter Saltonstall, president and CEO of the National Organization for Rare Disorders (NORD), “so there’s a huge opportunity there to try to develop more drugs.”

Saltonstall spoke today with five other panelists at Boston Children’s Hospital’s Global Pediatric Innovation Summit + Awards in a session titled, “Rare diseases: Lessons from the path less chosen.” David Meeker, MD, president and CEO of Genzyme, moderated.

Just as rare as the diseases are people who have knowledge about them. Most physicians—even in tertiary care hospitals—may have seen just one or two cases of a given rare disease in their careers—if any. And there’s only a limited number of research labs studying these diseases. “A lot of patients with rare disease come through the hospital, and move on and are lost to follow up and are never studied,” noted panelist Alan Beggs, PhD, director of Boston Children’s Manton Center for Orphan Disease Research.

Moreover, once a patient is studied and a gene discovered, the journey is just beginning. How does the disease actually work, and how do you counter it? Say you find that the disease involves loss of a vitally important enzyme. How do you get that enzyme back into a patient’s cells? “There’s a lot of cellular biology to be done once we know an enzyme,” said panel Albert Seymour, PhD, head of global research for Shire Pharmaceuticals. “The challenge from an industry perspective is how to take that knowledge and translate it into something that has legs for therapeutic development.”

There are some advantages in being rare. Patients are desperate and therefore highly engaged, and are able to find each other like never before through the Internet. Some parents are organizing their own clinical studies and even launching startup companies.

The FDA has itself begun reaching out to the rare disease community. The agency has made the approval process much less onerous for orphan drugs, where patient populations are by definition small, often very sick and lacking any other option—so the risks are seen as more acceptable. Last year, 37 percent of the drugs approved by the FDA were for orphan diseases, said panelist Marlene Haffner, MD, an FDA veteran who now runs a company that facilitates orphan drug development.

In rare disease, “you can’t expect 1,000- to 3,000-person trials,” said Robert (Skip) Nelson, an ethicist with the FDA’s Office of Pediatric Therapeutics. He cited the example of Myozyme, a treatment for Pompe disease, an often fatal metabolic disorder affecting an estimated 1 in 40,000 births. “Myozyme was approved based on 18 people.”

Though small, the trial was global, with patients flown to several study centers from countries all over the world. “It’s only a patient community coming together and beginning to organize that allowed it to be approachable,” said Genzyme’s Meeker.

With so many rare diseases—and some, like cystic fibrosis and Duchenne muscular dystrophy, now known to include many sub-diseases—there are a lot of questions about how to translate one therapeutic success to other diseases. And even more questions about how to create a workable, sustainable financial model.

“Can we afford [rare disease] products that cost $200,000 a year to treat each patient?” asked Nelson. “There’s going to have to be innovation in how we move forward.”