[Updated, 8/6/18, see below] By next weekend, the FDA could for the first time approve a medicine that uses a biological trick that was only discovered two decades ago: RNA interference, which silences a gene before it can make a harmful protein. That medicine is patisiran (Onpattro), from Alnylam Pharmaceuticals (NASDAQ: [[ticker:ALNY]]).
An approval wouldn’t just be a scientific milestone. It’s a medical one, too, for patients with a rare, progressive, and deadly disease called hereditary transthyretin amyloidosis (hATTR).
“We’ve been waiting many, many, many years for a treatment,” says Mary O’Donnell, the president of the nonprofit Amyloidosis Foundation. “We have our fingers crossed.”
Doctors in the U.S. try to manage peoples’ symptoms or slow the progression of hATTR with a generic drug meant for other diseases, but nothing has yet been specifically approved for hATTR, which causes nerve damage, heart problems, and ultimately an early death. In a study that included 225 patients, patisiran—an infusion given at a clinic once every three weeks—has shown that it might not just halt the destructive biological process that underlies the disease, but in some cases, improve nerve function. Its approval would follow a nod in Europe in July for a similar drug, inotersen from Akcea Therapeutics (NASDAQ: [[ticker:AKCA]]). The FDA should decide on an inotersen approval by early October.
“The conversation is changed by these two drugs,” says John Berk, the assistant director of the Amyloidosis Center at Boston University School of Medicine, and an investigator in trials for both patisiran and inotersen. (Berk co-authored two papers on the two drugs that the New England Journal of Medicine published in July.)
Though its exact prevalence is unknown, hATTR is estimated to affect 50,000 people worldwide. People who have the disease make a mutated version of the protein transthyretin, which builds up in misfolded clumps, causing damage to a variety of tissues around the body. Some patients suffer just the nerve damage, an insidious process that starts with numbness in the toes, then feet, and moves upwards. Others suffer a corrosion of the heart’s wiring that can lead to heart failure and death.
If the disease affects the heart, people might live just a few years past diagnosis, says Berk. The prognosis is better for those with just nerve damage—up to a 15-year life expectancy—but the effects are still debilitating. The disease can rob mobility and put people in wheelchairs and eventually on bedrest; they can die from infected sores and sepsis. Most patients have both nerve and heart problems, Berk says.
Much is unknown about hATTR. It is often mistaken for other medical issues involving either nerve or heart damage. It can take years to get the proper diagnosis after a battery of tests. There are no approved blood tests, for example, that look for misfolding TTR. (Alnylam and Akcea are offering free genetic testing to help find patients.)
hATTR is also caused by more than 120 different mutations, and each might lead to a different disease trajectory—it could start in someone’s early 30s, or late 50s. O’Donnell knows of a musician whose mother and aunt died from hATTR in their 30s, for example. Now their age, he has no bowel control. “Somehow or other, he’s just bulldogging through,” she says.
The only treatments to date in the U.S. are liver transplants or diflunisal, a generic anti-inflammatory drug used off label to “stabilize” the TTR protein and slow the progressive nerve damage. But liver transplants are risky, tough to get, and don’t always work. The aunt and mother O’Donnell spoke of both
