Pfizer vyndaqel EU approved the first attr-cm treatment drug

Pfizer recently announced that the European Commission (EC) has approved vyndaqel (tafamidis), a 61 mg oral capsule once a day, for the treatment of adult patients with wild-type or genetic ttr-cm Prior to this approval, treatment options for attr-cm patients were limited to symptom management and, in a few cases, to heart (or heart and liver) transplantation Attr-cm is a rare life-threatening disease characterized by the accumulation of a misfolded protein called amyloid protein in the heart, which is defined as restrictive cardiomyopathy and progressive heart failure On average, patients survive only 2-3.5 years after diagnosis In 2011, the European Union approved a different type of vyndaqel (tafamidis megumene) 20mg capsule for the treatment of attr-pn in adult patients with stage 1 symptomatic polyneuropathy to delay the damage of peripheral nerve function For attr-cm, tafamidis 61mg capsule is equivalent to 80mg tafamidis megumene dose (4 20mg capsules) It is a capsule developed for the convenience of patients to take one capsule every day These two drugs have the same active ingredient tafamidis, but due to different recommended doses, they can not be replaced each other It is worth mentioning that vyndaqel is the first and only drug approved in the European Union to treat attr-cm, and the only drug proven to reduce the mortality and cardiovascular related hospitalization rate of wild-type or genetic attr-cm patients In the European Union, vyndaqel is also the first drug to treat both attr-cm and attr-pn In the United States, vyndaqel (tafamidis meglumine) and vyndamax (tafamidis) were approved by FDA in early May 2019, becoming the first and only drug to treat attr-cm The two drugs are the first in class transthyroxin stabilizers tafamidis Paul Levesque, Pfizer's global president of rare diseases, said: "previously, the European Union has not approved drugs for the treatment of attr-cm patients Today's approval is a major milestone for these patients and reflects our strong commitment to providing breakthrough drugs to patients with rare diseases In addition, with today's milestone, vyndaqel is now the first EU approved drug to have two formulations for the treatment of PTH amyloidosis: one for cardiomyopathy and one for stage 1 polyneuropathy " Thibaud damy, former chairman of the heart failure and cardiomyopathy organization of the French Society of Cardiology and coordinator of the referral center for cardiac amyloidosis in France, said: "before today, the European Community for transforming thyroxine protein amyloidosis urgently needs new treatment programs to improve the prognosis of patients with cardiomyopathy Vyndaqel is a significant improvement for patients because it can significantly reduce all-cause mortality and cardiovascular related hospitalizations in patients with wild-type or inherited attr-cm " The European Commission approved vyndaqel, based on data from the critical phase III clinical study attr-act, which is the first and only successful global, double-blind, randomized, placebo-controlled clinical trial to investigate an attr-cm pharmacological therapy A total of 441 patients were enrolled in the study, including patients with variant or inherited attr-cm and patients with wild-type attr-cm (not inherited, but likely to occur with age) The main analysis results showed that during the 30-month treatment period: (1) compared with placebo, vyndaqel (tafamidis megumene) significantly reduced the all-cause death and cardiovascular related hospitalization rate of wild-type and genetic type attr-cm patients (P = 0.0006) (2) Compared with placebo group, vyndaqel reduced all-cause mortality and all-cause hospitalization by 30% (P = 0.026) and 32% (P < 0.0001) respectively (3) Compared with placebo, vyndaqel reduced the risk of all-cause death in all subgroups (wild-type, genetic, nyha-i, - II, - III functional classification): the risk of death in the wild-type subgroups (HR = 0.71, 95% CI: 0.474-1.052) and the genetic subgroups (HR = 0.69, 95% CI: 0.408-1.167) by 29% and 31%, respectively (4) Across the wild-type and genetic subgroups, vyndaqel showed a consistent reduction in all aspects of patients' ability to move as assessed by the 6-minute walk test (6MWT) and quality of life as assessed by the Kansas City Cardiomyopathy Questionnaire (KCCQ), compared with placebo (5) In the study, vyndaqel was well tolerated and had comparable safety with placebo The approval is also based on an evaluation of tafamidis 61mg from the free acid type The evaluation results showed that a 61 mg tafamidis free acid capsule was equivalent to 80 mg tafamidis megumene (4 20 mg capsules) The safety of 61mg dose was not evaluated in attr-act Tafamidis 61mg capsule is developed for the convenience of patients and can be used for daily use Tafamidis molecular structure (from Wikipedia) Attr amyloidosis is a rare progressive disease, which is characterized by abnormal accumulation of amyloid in human organs and tissues Amyloidosis can affect many organs and tissues of the body, including the peripheral nervous system, as well as organs such as the heart, kidney, gastrointestinal tract and eyes Attr-cm and attr-pn are two manifestations of the disease Attr-cm is a rare, fatal and seriously underdiagnosed disease associated with progressive heart failure Attr-cm is caused by the instability of a transporter called TTR, which consists of four identical subunits (tetramers) In attr-cm, heart failure occurs when the unstable tetramer dissociates, resulting in the accumulation of misfolded proteins into amyloid fibers, which are mainly deposited in the heart Tafamidis is an oral small molecule drug, which can stabilize TTR In the United States and the European Union, tafamidis was awarded orphan drug qualification to treat attr-cm in 2011 In 2017, FDA also granted tafamidis fast track status; in March 2018, MHLW granted tafamidis sakigake qualification; in May 2018, FDA granted tafamidis breakthrough drug qualification.