Benzinga | Dec 20, 2021 04:32PM EST

Pfizer Announces It's VYNDAQEL/VYNDAMAX Reduced The Risk Of All-Cause Mortality By 41% Among Patients With Transthyretin Amyloid Cardiomyopathy, Five-Year Follow-Up Data Demonstrate

Pfizer Inc. (NYSE:PFE) announced today the publication of a post-hoc, interim analysis showing that treatment with VYNDAQEL(r) (tafamidis meglumine) / VYNDAMAX(r) (tafamidis) provided a clinically significant survival benefit at five years for patients with transthyretin amyloid cardiomyopathy (ATTR-CM). This analysis from the Phase 3 Transthyretin Amyloid Cardiomyopathy Clinical Trial (ATTR-ACT) and its long-term extension (LTE) study was published in Circulation: Heart Failure.

In ATTR-ACT, patients were randomized to receive VYNDAQEL 80 mg, 20 mg or placebo, and upon study completion at 30 months could enroll in the LTE study. In the LTE study, patients who had been treated with VYNDAQEL 80 mg continued this therapy, then transitioned to the bioequivalent single-capsule VYNDAMAX. Patients treated with placebo in ATTR-ACT were randomized to receive either VYNDAQEL 80 mg or 20 mg in the LTE study and were subsequently transitioned to VYNDAMAX. VYNDAMAX 61 mg is bioequivalent to VYNDAQEL 80 mg but is not interchangeable on a per-mg basis.

"The results from this analysis build upon the positive primary results from the pivotal trial, ATTR-ACT, and reinforce that VYNDAQEL and VYNDAMAX have the potential to significantly extend survival for patients with ATTR-CM," said Brenda Cooperstone, M.D., Chief Development Officer, Rare Disease, Pfizer Global Product Development. "VYNDAQEL and VYNDAMAX represent a breakthrough for these patients who have no other approved medicines and the ATTR-ACT and the LTE study demonstrate that earlier treatment is crucial for patients with ATTR-CM."

In ATTR-ACT, treatment with VYNDAQEL demonstrated a 30% reduction in mortality at 30 months compared to placebo. With a median follow up of nearly five years, the analysis published in Circulation: Heart Failure showed a clinically significant 41% reduction in the risk of all-cause mortality among patients who received continuous VYNDAQEL/VYNDAMAX treatment (median follow up 58.5 months) compared to patients who first received placebo in ATTR-ACT before transitioning to VYNDAQEL/VYNDAMAX in the LTE (median follow up 57.1 months; HR: 0.59; 95% CI: 0.44--0.79; P<0.001). Median survival was 67 months (95% CI: 47.0--N/E) in the continuous treatment arm compared to 35.8 months (95% CI: 29.7--41.1) in the placebo to treatment arm. The preliminary five-year survival rate was 53.2% in the continuous treatment arm versus 32.4% in the placebo to treatment arm.

"The survival benefit seen in the primary analysis is further supported by these long-term results, emphasizing the importance of early diagnosis and treatment with VYNDAQEL/VYNDAMAX for patients living with ATTR-CM," said Perry Elliott, M.D., Professor of Cardiovascular Medicine, Director of the Institute for Cardiovascular Science, University College London and lead author of the analysis. "While there has been progress in the diagnosis of ATTR-CM due to increased awareness and improvements in diagnostic approaches, the condition is still overlooked, preventing patients from benefiting from disease modifying treatment."

Reduction in mortality was consistent across all sub-groups, including wild-type and hereditary ATTR-CM with a 39% reduction in the risk of all-cause mortality in patients with wild-type ATTR-CM (HR: 0.61; 95% CI: 0.43--0.87; P=0.006), and a 43% reduction in patients with hereditary ATTR-CM (HR: 0.57; 95% CI: 0.33--0.99; P=0.05) in patients receiving continuous VYNDAQEL/VYNDAMAX treatment, compared with the placebo to treatment arm. In addition, the analysis demonstrated a 44% reduction in the risk of all-cause mortality in patients with baseline NYHA class I or II (HR: 0.56; 95% CI: 0.38--0.82; P=0.003), and a 35% reduction in patients with baseline NYHA class III (HR: 0.65; 95% CI: 0.41--1.01; P=0.06) in the continuous treatment arm compared with the placebo to treatment arm. In ATTR-ACT, VYNDAQEL had a safety profile comparable to placebo. No new safety concerns were identified throughout the LTE study and adverse events remained similar to placebo.

VYNDAQEL and VYNDAMAX are indicated for the treatment of the cardiomyopathy of wild-type or hereditary transthyretin-mediated amyloidosis in adults to reduce cardiovascular mortality and cardiovascular-related hospitalization. They are the first and only medicines approved for the treatment of wild-type and hereditary ATTR-CM, which is underrecognized and underdiagnosed in patients with heart failure. This rare, progressive and life-threatening disease is caused by unstable transthyretin proteins that misfold and aggregate into amyloid fibrils that can build up in the heart and other parts of the body. The buildup of transthyretin amyloid in the heart causes the heart muscle to stiffen over time, eventually leading to heart failure. Once diagnosed, the median life expectancy in untreated patients with ATTR-CM is approximately two to 3.5 years.