Vyndaqel well tolerated by adults with early-stage FAP in France

Researchers analyzed data from 22 clinical centers, focusing on 336 patients

Margarida Maia, PhD avatar

by Margarida Maia, PhD |

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The oral medication Vyndaqel (tafamidis meglumine) appears to be well tolerated by adults with familial amyloid polyneuropathy (FAP) in France, where the treatment is often started at an early stage of the disease, a real-world study finds.

Easy access to a combination of genetic testing and a minimally invasive biopsy, where a small piece of affected tissue is removed, may shorten the time to diagnosis, said its researchers, who noted it may also allow treatment to be started early, when it’s likely to be most effective. The study, “Transthyretin amyloid polyneuropathy in France: A cross-sectional study with 413 patients and real-world tafamidis meglumine use (2009–2019),” was published in Revue Neurologique. It was funded by Pfizer, which markets Vyndaqel.

FAP is caused by mutations that result in a faulty version of the protein transthyretin, which breaks down into its basic units that form toxic clumps that tend to build up mostly in nerves outside the brain and spinal cord, interfering with how they function. In some patients, these aggregates can accumulate in the heart muscle, causing heart damage, or cardiomyopathy.

Vyndaqel binds to the faulty transthyretin, making it more stable and keeping it from breaking down. This should prevent toxic aggregates from forming and slow the disease’s progression.

It’s approved in Europe, but not the U.S., to delay nerve damage caused by FAP in adults with Coutinho stage 1, or early-stage, disease. A new formulation is approved in Europe and U.S. for adults with transthyretin amyloid cardiomyopathy, a FAP-related disease where toxic transthyretin clumps mainly damage the heart.

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Evaluating Vyndaqel’s safety and efficacy

Here, researchers evaluated the patterns of use of Vyndaqel, along with its safety and effectiveness, in a real-world setting by analyzing data from 22 clinical centers in France up to October 2019. They identified 464 adults who took Vyndaqel outside of trials since 2009, when the therapy was first used in the country through an early access program. The treatment was formally approval in August 2011.

They then focused on the 240 patients diagnosed with FAP (51.7%) and 96 with a mixed phenotype (20.7%), that is, having both polyneuropathy and cardiomyopathy symptoms.

Most patients were men and their mean age was 56.9 for the FAP group and 63.5 years for the mixed group. Nearly half (46.7%) carried the Val30Met mutation, the most common cause of FAP. Most patients in both groups had a Coutinho stage 1.

More than two-thirds (72.9%) of FAP patients started Vyndaqel at an early stage of the disease. Patients with no manifest symptoms of FAP (Coutinho stage 0) were more likely to continue treatment with Vyndaqel than those with more advanced disease stages (Coutinho stages 1 to 3). The treatment duration was also superior in the FAP group than in the mixed group (median, 6 vs. 3.42 years).

Coutinho stage data from 174 FAP patients showed that, after treatment, most (71.8%) maintained their stage, 36 (20.7%) progressed to a more advanced score, and 13 (7.5%) moved to a less severe stage. Fourteen FAP patients (5.8%) and 14 mixed phenotype patients (14.6%) were reported to have died.

Vyndaqel was generally well tolerated. Of the 336 patients with safety data, 20 had side effects that were likely related to Vyndaqel. Two had serious side effects likely related to the treatment.

The treatment was discontinued by 69 FAP and 36 mixed phenotype patients, mostly due to the emergence of new symptoms in the FAP group (49.6%) and change of treatment in the mixed group (30.6%). A liver transplant was conducted only among those with early-onset FAP caused by a Val30Met mutation, and in more than half of them (58.3%).

In France, people with FAP “are usually identified early thanks to the national network and the help of diagnosis combining genetic testing and [minimally] invasive biopsies,” allowing timely treatment, the researchers wrote. “Treating an orphan disease with an easy-to-use, simple, well-tolerated drug as a first-line treatment was an opportunity for both patients and physicians, knowing that the only therapeutic option was liver transplantation.”

They said Vyndaqel “may prevent or delay surgical intervention such as liver transplantation.”