Onpattro (patisiran) is not approved for cardiomyopathy. The FDA approved it in 2018 specifically for nerve damage (polyneuropathy) caused by hereditary transthyretin amyloidosis in adults. Its manufacturer sought approval for heart-related use, but the FDA rejected that application in late 2023, citing that the drug’s benefits for cardiomyopathy had not been clearly established.
What Onpattro Is Approved For
Onpattro treats polyneuropathy, the progressive nerve damage that occurs when a misfolded protein called transthyretin (TTR) builds up in nerve tissue. In hereditary transthyretin amyloidosis (hATTR), a genetic mutation causes the liver to produce an unstable form of TTR that clumps into amyloid deposits throughout the body. These deposits can damage nerves, the heart, or both.
The drug works by silencing the gene that tells the liver to make TTR protein. It uses a technology called RNA interference to intercept the genetic instructions before they’re carried out, which sharply reduces the amount of TTR circulating in the blood. With less TTR being produced, fewer amyloid deposits form, and nerve damage slows or stabilizes.
Why the FDA Rejected It for Cardiomyopathy
Alnylam Pharmaceuticals tested Onpattro in patients with transthyretin amyloidosis affecting the heart (ATTR-CM) in a clinical trial called APOLLO-B. At 12 months, patients receiving the drug walked about 15 meters farther on a six-minute walk test than those on placebo, and their quality-of-life scores improved slightly while the placebo group’s scores declined. Both differences were statistically significant but modest.
The problem was the harder outcomes. Onpattro did not reduce deaths, hospitalizations, or urgent heart failure visits compared to placebo. The FDA issued a Complete Response Letter in October 2023, stating that “the clinical meaningfulness of patisiran’s treatment effects for the cardiomyopathy of ATTR amyloidosis had not been established.” Notably, the FDA raised no concerns about safety, study conduct, or drug quality. The issue was purely whether the improvements were large enough to matter for patients with heart disease.
Off-Label Use in Mixed Cases
There is one scenario where Onpattro may already be used in patients with heart involvement. Some people with hereditary transthyretin amyloidosis have both nerve damage and cardiomyopathy at the same time, a “mixed phenotype.” Because Onpattro is approved for the polyneuropathy component, doctors can prescribe it to these patients. The drug reduces TTR production throughout the body, so it may offer some cardiac benefit even though the official indication is for nerve disease. This is not the same as an approval for cardiomyopathy, but it means some patients with heart symptoms are already receiving the drug.
What Is Approved for ATTR Cardiomyopathy
The first and most established treatment for ATTR cardiomyopathy without neuropathy is tafamidis, a TTR stabilizer. Rather than reducing TTR production the way Onpattro does, tafamidis works by holding the TTR protein together in its normal shape so it’s less likely to break apart and form amyloid deposits. In its pivotal trial, tafamidis significantly reduced both deaths and cardiovascular hospitalizations over 30 months, along with preserving walking ability and quality of life. It remains the benchmark treatment for ATTR-CM.
A newer option is gaining ground. Vutrisiran (brand name Amvuttra), made by the same company as Onpattro, uses a similar gene-silencing approach but is given as a subcutaneous injection rather than an intravenous infusion. In the HELIOS-B trial, vutrisiran significantly reduced the risk of death and recurrent cardiovascular events in ATTR-CM patients compared to placebo, and it preserved both functional capacity and quality of life. This is the next-generation drug that Alnylam has been developing as its cardiac-focused treatment, and its stronger clinical results help explain why the company did not pursue further efforts to get Onpattro approved for the heart.
How ATTR-CM Differs From Other Cardiomyopathies
It’s worth understanding that ATTR cardiomyopathy is a specific type of heart disease caused by amyloid protein deposits in the heart muscle. It is not the same as the more common forms of cardiomyopathy caused by high blood pressure, coronary artery disease, or viral infections. Onpattro, tafamidis, and vutrisiran all target the transthyretin protein specifically. None of them would be relevant for other types of cardiomyopathy.
ATTR-CM comes in two forms. The hereditary form results from a genetic mutation and can appear as early as the 50s or 60s. The wild-type form, once called senile cardiac amyloidosis, involves normal (non-mutated) TTR protein that misfolds with aging and predominantly affects men over 70. Both forms cause the heart walls to thicken and stiffen, leading to heart failure symptoms like shortness of breath, fatigue, and fluid retention. Diagnosis typically involves cardiac imaging, sometimes a specific type of nuclear scan, and occasionally a biopsy or genetic test.
If you or someone you know has been diagnosed with ATTR amyloidosis affecting both nerves and the heart, Onpattro may be part of the treatment plan through its existing approval for polyneuropathy. For isolated cardiomyopathy without significant nerve involvement, the current approved options center on tafamidis, with vutrisiran emerging as an alternative with strong clinical trial data supporting its cardiac benefits.