Research presented this week at the European Society of Cardiology (ESC) Congress in Munich suggests a new treatment may be emerging for transthyretin amyloid cardiomyopathy—a condition previously thought to be rare and untreatable.
In a double-blind trial published in the New England Journal of Medicine, the 264 patients who were randomized to tafamidis had lower all-cause mortality rates than the 177 who were randomized to a placebo (29.5 percent versus 42.9 percent). The relative risk reduction was calculated at 30 percent over the 30-month trial.
Also, tafamidis was associated with a 32 percent reduced risk of cardiovascular-related hospitalizations and a lesser rate of decline on a six-minute walk test and a quality of life questionnaire at 30 months.
Lead author Mathew S. Maurer, MD, and colleagues noted there were fewer cardiovascular hospitalizations with tafamidis across all subgroups, other than in patients with the most severe cases of heart failure included in the trial—New York Heart Association functional class III.
“We speculate that the higher hospitalization rate observed in this group is attributable to longer survival during a more severe period of disease, underscoring the importance of early diagnosis and treatment of this fatal, progressive disease, which can be difficult to diagnose,” Maurer et al. wrote. “Given the progressive nature of the disease and the mechanism through which tafamidis reduces amyloidogenesis—by specifically stabilizing transthyretin tetramers—the drug is expected to have greater benefit when administered early in the disease course.”
Cardiac amyloidosis occurs when deposits of the amyloid protein affect the heart tissue, which can stiffen and thicken the muscle and impair its function. The life expectancy after diagnosis is about three years, according to the researchers.
But the new findings could generate fresh hope for these patients, said the authors of a related editorial.
“Given the dearth of acceptable treatments for this disorder, these robust efficacy results, combined with a benign safety profile, suggest an important role for tafamidis in the treatment of transthyretin amyloid cardiomyopathy,” wrote C. Crista Quarta, MD, and Scott D. Solomon, MD, in NEJM.
The editorialists agreed with Maurer and colleagues that tafamidis may be most effective when provided early in the disease’s progression.
“Reductions in cardiovascular-related hospitalizations were seen only after nine months, and all-cause mortality after 18 months, which may reflect the time necessary to influence the underlying pathology,” they noted. “It is possible that by slowing or halting amyloid deposition, tafamidis may allow the activation of local recovery processes that progressively result in a remodeling of the amyloid deposits, a reduction in the strain on the cardiac walls, and ultimately in a clinical benefit.
“Once amyloid has caused irreversible organ damage, disease-modifying treatments may be less likely to be effective.”
Notably, the trial was sponsored by Pfizer, the manufacturer of tafamidis. The drug has received Fast Track and Breakthrough Therapy designations from the FDA, but still isn’t approved for commercial distribution.
“We believe the ATTR-ACT study findings bring us a significant step closer to our goal of providing an urgently needed therapy for a serious and often fatal disease,” Brenda Cooperstone, MD, a Pfizer senior vice president, said in a press release. “We look forward to continuing discussions with global regulatory authorities about the potential of tafamidis as a treatment option for people living with (transthyretin amyloid cardiomyopathy).”
Daniel joined TriMed’s Chicago editorial team in 2017 as a Cardiovascular Business writer. He previously worked as a writer for daily newspapers in North Dakota and Indiana.