Pfizer’s VYNDAQEL®/VYNDAMAX® Demonstrates 41% Reduction in All-Cause Mortality in ATTR-CM Patients Over Five Years

December 21, 2021 /BioValleyBIOON/ --Pfizer(Pfizer) recently announced the results of an ad hoc interim analysis, which showed that: during 5 years of treatment, Vyndaqel (tafamidis meglumine) / Vyndamax (tafamidis) provided clinically significant survival benefits for patients with transthyretin amyloid cardiomyopathy (ATTR-CM).All-cause mortality reduced by 41%. This analysis report comes from the Phase 3 ATTR-ACT and Long-Term Extension (LTE) study, with data published in the international medical journal *Circulation: Heart Failure*.

These long-term results further support the survival benefits observed in the preliminary analysis, emphasizing the importance of early intervention for ATTR-CM patients.DiagnosisThe importance of early treatment with Vyndaqel/Vyndamax. Before Vyndaqel/Vyndamax was approved, treatment options for ATTR-CM patients were limited to symptom management and, in rare cases, heart (or heart and liver) transplantation.ATTR-CM is a rare and life-threatening disease characterized by the accumulation of a misfolded protein called amyloid in the heart., defined as restrictive cardiomyopathy and progressive heart failure. On average, patients who are diagnosed and left untreated survive only 2-3.5 years.

In the ATTR-ACT study, patients were randomly assigned to receive Vyndaqel 80mg, 20mg, or placebo, and could enroll in the LTE study after completing the 30-month study. In the LTE study, patients who previously received Vyndaqel 80mg continued this treatment and then transitioned to the bioequivalent single capsule Vyndamax. In the LTE study, patients who received placebo treatment in the ATTR-ACT study were randomly assigned to receive Vyndaqel 80mg or 20mg, followed by a switch to Vyndamax. Vyndamax 61mg is bioequivalent to Vyndaqel 80mg but is not interchangeable on a milligram basis.

In the ATTR-ACT study, at 30 months of treatment, Vyndaqel reduced mortality by 30% compared to placebo. After a median follow-up of nearly 5 years, an analysis published in *Circulation: Heart Failure* showed that, compared to patients who first received placebo in the ATTR-ACT study and then transitioned to Vyndaqel/Vyndamax in the LTE study (median follow-up of 57.1 months), patients receiving continuous Vyndaqel/Vyndamax treatment (median follow-up of 58.5 months) had a 41% reduction in all-cause mortality (HR=0.59; 95% CI: 0.44–0.79; p<0.001), which was clinically significant. The median survival time in the continuous treatment group was 67 months (95% CI: 47.0–N/E), compared to 35.8 months (95% CI: 29.7–41.1) in the placebo group.The initial 5-year survival rate was 53.2% in the continuous treatment group and 32.4% in the placebo group.。

Mortality reduction was consistent across all subgroups., including wild-type and hereditary ATTR-CM. Compared with the placebo group, the risk of all-cause mortality was reduced by 39% (HR=0.61; 95% CI: 0.43–0.87; p=0.006) in wild-type ATTR-CM patients receiving continuous Vyndaqel/Vyndamax treatment.GeneticsThe risk of ATTR-CM in patients was reduced by 43% (HR=0.57; 95% CI: 0.33–0.99; p=0.05).

Moreover, the analysis showed that, compared with the placebo group, the risk of all-cause mortality was reduced by 44% (HR=0.56; 95% CI: 0.38–0.82; p=0.003) in patients receiving continuous Vyndaqel/Vyndamax treatment who were at NYHA class I or II at baseline, and by 35% (HR=0.65; 95% CI: 0.41–1.01; p=0.06) in those at NYHA class III at baseline. In the ATTR-ACT study, the safety of Vyndaqel was comparable to that of the placebo. No new safety issues were identified throughout the LTE study, and adverse events were similar to those of the placebo.

Brenda Cooperstone, MD, Chief Development Officer of Rare Diseases at Pfizer Global Product Development, stated: "The results of this analysis build on the positive initial outcomes of the pivotal ATTR-ACT trial and further demonstrate that Vyndaqel and Vyndamax have the potential to significantly extend the survival of patients with ATTR-CM. These patients have no other approved medications, and Vyndaqel and Vyndamax represent a treatment breakthrough for them. The ATTR-ACT and LTE studies show that early treatment is crucial for patients with ATTR-CM."

Tafamidis Molecular Structure (from Wikipedia)

ATTR Amyloidosis is a rare progressive disease characterized by the abnormal accumulation of amyloid deposits composed of misfolded transthyretin protein in human organs and tissues. Amyloidosis can affect many organs and tissues of the body, including the peripheral nervous system, as well as the heart, kidneys, gastrointestinal tract, and eyes. ATTR-CM and ATTR-PN are two manifestations of this disease.

Transthyretin Amyloid Cardiomyopathy (ATTR-CM) is a rare, fatal, and severeDiagnosisThe disease is associated with progressive heart failure. ATTR-CM is caused by the instability of a transport protein called transthyretin (TTR), which consists of four identical subunits (tetramer). In ATTR-CM, heart failure occurs when the unstable tetramer dissociates, leading to misfolded proteins aggregating into amyloid fibrils and primarily depositing in the heart, ultimately resulting in heart failure. Once diagnosed, the average life expectancy of untreated ATTR-CM patients is only 2-3.5 years.

Vyndaqel and Vyndamax are two oral formulations of the first-in-class transthyretin stabilizer tafamidis.Tafamidis selectively binds to transthyretin, stabilizes the tetramer of transthyretin transport protein, and slows the formation of amyloid that leads to ATTR-CM.As of now, tafamidis has been approved for the treatment of ATTR-CM in 55 countries, including the United States and the European Union.

Vyndamax 61mg and Vyndaqel 80mg are from the United StatesFDAThe only approved dose for the treatment of ATTR-CM. Vyndamax 61mg is a once-daily oral capsule developed for patient convenience, with one Vyndamax 61mg capsule being bioequivalent to Vyndaqel 80mg (four 20mg capsules), but not interchangeable on a mg basis.

In 2011, Vyndaqel 20mg was first approved in the EU for the treatment of transthyretin amyloidosis (ATTR-PN) in adult patients with stage 1 symptomatic polyneuropathy to delay peripheral nerve function impairment. Currently, Vyndaqel 20mg has been approved for the treatment of ATTR-PN in more than 40 countries. In the United States, Vyndaqel and Vyndamax have not been approved for the treatment of ATTR-PN. (Bioon.com)

Source of Original Text:Pfizer’s VYNDAQEL®/VYNDAMAX® Reduced the Risk of All-Cause Mortality by 41% Among Patients with Transthyretin Amyloid Cardiomyopathy, Five-Year Follow-Up Data Demonstrate