With New Drugs in the Offing, Treatment Cost of ATTR-CM Is Projected to Climb | AMCP Nexus 2024

By some accounts, spending worldwide on treatment of patients with transthyretin amyloidosis cardiomyopathy (ATTR-CM) is projected to increase by more than 30% over the next several years, including in the United States. The cost on a per member, per month basis for U.S. healthcare plans is expected to remain relatively low, although it will increase as a share of the spending on the rare diseases categories, Timothy O’Shea, Pharm.D., M.S., director of specialty pharmacy at Horizon Blue Cross Blue Shield of New Jersey, said in a session yesterday devoted to ATTR-CM at the 2024 Academy of Managed Care Pharmacy (AMCP) Nexus meeting in Las Vegas.

ATTR-CM has caught the eye of drug developers, and several new drugs are in phase 3 trials.

Systemic amyloidosis is characterized by the buildup of amyloid deposits in the heart, kidneys and other organs. It can lead to organ dysfunction and death. The condition can be inherited or acquired. ATTR-CM is one of type of systemic amyloidosis in which misshapen transthyretin (TTR) protein accumulates in the myocardium of the heart. ATTR-CM can cause a variety of heart problems, including heart failure and arrhythmias. Black individuals and men are disproportionately affected. The risk also increases with age and among those with a family history. There’s a great deal of uncertainty about the prevalence of ATTR-CM in the U.S. because the condition may often go undiagnosed, but by some accounts at least 50,000 people are affected.

Timothy O'Shea, Pharm.D., M.S.

O’Shea said that the drug spend for ATTR-CM is low at this time because of the disease’s rarity. “But given that, even though utilization is going to be low [and] spend is going to be low, when we look at it in the aggregate of the rare disease category, we're seeing big increases,” O’Shea said.

O’Shea said payers are grappling with overall rare disease spending by optimizing effective drug management and understanding the cost effectiveness of therapies. For optimizing effective drug management, O’Shea mentioned a checklist for pharmacy benefit and medical benefits, which included utilization projection, formulary coverage, utilization management, pharmacy case management and assessment of real-world data.

In September 2024, the Institute for Clinical and Economic Review (ICER) the cost-effectiveness research organization, published a report on three drugs used to treat ATTR-CM: tafamidis, an oral drug; acoramidis, an oral drug; and Amvuttra (vutrisiran), delivered by subcutaneous injection. The ICER experts said there was a high degree of certainty of substantial health benefits from tafamidis and Amvuttra, and a high degree of certainty of at least a small health benefits from acoramidis.

Drug developers are interested in finding new treatments for ATTR-CM for a number of reasons, including the overall demographic trend toward an older population and an increasing number of diagnoses. Currently, there are five commercially available therapies. They cost from approximately $22,332 per month to $41,583 per month, so the cost for payers and patients is looming as an issue and could be an obstacle to care and coverage.

Tafamidis is the only currently FDA-approved therapy. Amvuttra, Onpattro (patisiran) and Wainua (eplontersen) are among the drugs used to treat other amyloidosis-related conditions that are used off-label to treat ATTR-CM, but a number of trials are underway with an eye toward getting FDA approval and adding ATTR-CM as an indication.

“The drugs that we have available right now only work on stopping that production of the TTR protein to reduce further deposition in the tissue. We don’t currently have anything that can pull these fibril tissue, so recovery will be very slow for these patients because they have the wait for the body's catabolic processes to break it down,” Tyler Sandahl, Pharm.D., a clinical pharmacy specialist at Mayo Clinic, said in the session.

Tafamidis, sold under the brand name Vyndamax, and tafamidis meglumine, sold under the brand name Vyndqel, were approved by the FDA in 2019 for the treatment of ATTR-CM. The approved based on the results of the ATTR-ACT study, a phase 3, placebo-controlled.

Diflunisal, a nonsteroidal anti-inflammatory sold under the brand name Dolobid, has been shown to be well tolerated in select patients who have adequate renal function in a single-center, retrospective study. The drug increased TTR concentrations and decreased left atrial volume index, according to Sandahl.

Patisiran has also been investigated as a treatment for ATTR-CM, but was denied approval based on data from the APOLLO-B, which showed no statistically significant benefit in any of the secondary outcomes, including scores on a standardized survey designed to measure self-perception of health status, a composite of death from any cause, cardiovascular events, and change in 6-minute walk test. Further, there were more infusion-related reactions, arthralgia, and muscle spasms in the patisiran group compared with the placebo.

Alnylam Pharmaceuticals, Inc., the maker of Amvuttra, reported positive results from the HELIOS-B study of the drug as a treatment for ATTR-CM at the European Society of Cardiology Congress this summer. The results, published simultaneously in the New England Journal of Medicine, showed Amvuttra led to a 28% lower risk of death from any cause and recurrent cardiovascular events than placebo. Results on other end points tallied up in Amvuttra’s favor, and the number of adverse events were similar among those randomly assigned to be treated with Amvuttra and those randomly assigned to treatment with a placebo.

“[The company is] currently seeking expanded indication because right now vultrisiran is only approved [hereditary transthyretin-mediated amyloidosis with polyneuropathy],” Sandahl said. “I don't have information on when [an FDA approval] may be coming, but I would expect that in the coming months.”

The FDA is scheduled to announce whether it has approved acoramidis as a treatment for ATTR-CM in late November 2024. Although the development of drug has had some setbacks, BridgeBio has reported positive results from the ATTRibute-CM trial recently, including a post-hoc analysis at the Heart Failure Society of America’s annual meeting in September 2024.

Meanwhile, Ionis Pharmaceuticals is assessing eplontersen as an ATTR-CM treatment in the CARDIO-TTRansform trial, a multicenter, double-blind study that is designed to enroll approximately 1,400 participants worldwide.