For the last 3 decades, the only treatment that has been available for hereditary transthyretin-meditated amyloidosis was a liver transplant. The condition is caused by abnormal transthyretin proteins. These proteins build up in the kidneys, eyes, gastrointestinal tract, and peripheral nerves. It can cause low blood pressure, heart failure, and sudden death. Worldwide, it affects 50,000 people.
In August of this year, the amyloidosis community had their hope renewed with the approval of a new therapy. A treatment using RNA was approved by the FDA. It was the first ever treatment which utilized RNA to receive approval. The treatment uses siRNA to stop the production of the transthyretin protein. This is significant because unlike other approved treatments for amyloidosis, it doesn’t just treat the symptoms. By stopping the protein from replicating, it addresses the root cause of the disease.
Trials showed that the drug, called patisiran, could reduce the production of transthyretin by 80%. The phase 3 trial of the drug analyzed 225 patients across 19 different countries.
“The patisiran group had statistically significant improvements in neuropathy, quality of life, gait speed, and body mass index at 18 months.”
Patients on the drug had a 6-point decrease on the neuropathy scale. Those not on the drug suffered an increase of 28 points by the end of the 18 months. That difference is astounding. Previous studies have uncovered options to slow the progression of the disease, but up until this point nothing has actually increased patient’s function like patisiran.
The approval of this drug is huge not only for amyloidosis but for the development of similar treatments for other rare conditions. For instance, a study conducted at Harvard showed that RNAi could stop the HIV gene from replicating. Another showed that the treatment could prevent autoimmune hepatitis. Additionally, there are currently phase 3 trials in progress for hypercholesterolemia and hepatic porphyrias using RNAi therapies.
The research of RNA as a treatment method began way back in 2001, but various adverse effects caused excitement wane and research slow. This new approval has shown success is possible and will hopefully bring enthusiasm back to this research.
Patisiran is not a perfect fix for amyloidosis. Some of the same complications are present with the drug which are present with liver transplants. We also don’t know exactly how long the drug will remain efficacious in the body. But, it is progress. And progress is positive at any stage. This new development is extremely promising.
The best part about the amyloidosis approval is that it confirms the potential of RNA therapies for many other rare conditions. The ability to target the root of the problem could be life-changing for so many rare disease patients. We’re not there yet, and the process may be slow, but we’re headed the right direction for rare disease.
You can read more about this approval and RNA therapy research here.