Transthyretin-Mediated Amyloidosis Cardiomyopathy
The FDA has just approved the very first treatment for hereditary or wild-type transthyretin-mediated amyloidosis cardiomyopathy (ATTR-CM). ATTR-CM is a rare disease that occurs when amyloids, an abnormal protein, build up and form deposits within the heart. This causes the heart to become stiff and ultimately the condition results in heart failure. The hereditary form of the condition is caused by a mutation to the TTR gene whereas the wild-type form occurs without a mutation.
Unfortunately, most ATTR-CM patients aren’t diagnosed until after their condition is quite severe, simply because it is so rare. There are around 100,000 people living with the disease in the United States however only approximately 1-2% of these individuals have actually received their diagnosis. Clearly this condition is severely underdiagnosed. Patients are forced to see numerous specialists, take an obscene number of tests, and still have to wait years to know what’s wrong with them. Of course, during this time their disease only continues to progress. The median life expectancy after diagnosis is 2-3.5 years depending on the sub-type.
Up until now, the only therapies available for ATTR-CM patients were focused on symptom management. Additionally, some patients received liver or heart transplants. However, ultimately, this disease is defined as life-limiting with minimally effective therapies.
Thankfully, ATTR-CM patients now have a new option.
Newly Approved Treatment
Pfizer has just announced that they’ve received FDA approval for not one, but two, new treatments for ATTR-CM. They are called VYNDAQEL and VYNDAMAX. Both of these medications have the same active ingredient. They are oral transthyretin stabilizers. They work by slowing the formation of amyloids by binding to the transthyretin transport protein.
Pfizer’s dose recommendation for VYNDAQEL is four 20mg capsules each day, totaling 80mg. The recommendation for VYNDAMAX is a single capsule, which equates to 61mg. The two drugs are not substitutable on a mg basis. VYNDAMAX was created as a more convenient option for patients.
Both medications have shown their efficacy in a Phase 3 clinical trial. They were able to both reduce the frequency of hospital stays related to cardiovascular issues as well as reduce cardiovascular mortality. In other words, this new approval could literally save patient lives.
Concerned about accessibility? Pfizer has stated that they are committed to ensuring that eligible patients who have been prescribed the medication receive access. They plan to work with patients to make sure they understand the requirements of their insurance in addition to providing them financial assistance resources such as their own Pfizer Patient Assistance Program.
In 2011, VYNDAQEL was approved by the EU for transthyretin amyloid polyneuropathy (ATTR-PN). VYNDAQEL is now approved in 40 different countries for ATTR-PN (not including the United States).
In 2012 the drug was granted Orphan Drug Designation in both the United States and the EU for ATTR-CM. This same designation followed in Japan in 2018. The FDA later granted the drug Breakthrough Therapy Designation and Fast Track Designation, followed by Priority Review of its NDA for ATTR-CM.
The first approval of this medication as a ATTR-CM treatment came in March of this year in Japan. The country approved the therapy for both hereditary and wild-type forms of the disease. Currently, the European Medicines Agency (EMA) is also reviewing VYNDAQEL as a treatment for the condition.
Phase 3 Clinical Trial
This approval was based on a Phase 3 clinical trial titled ATTR-ACT. It was the first randomized, double-blind, placebo-controlled, global trial to test a pharmacological treatment for ATTR-CM. The treatment period was 30 months. During this time, VYNDAQEL was able to significantly reduce the frequency of hospitalizations related to cardiovascular issues as well as mortality.
In addition to these benefits, VYNDAQEL had significant effects on other health status factors. For instance, it reduced the performance decline in a 6 minute walk test and reduced the decline in overall health status of patients. Additionally, it proved to be well tolerated and had a positive safety profile. AE frequency was comparable in the treatment and placebo groups and a similar proportion of participants in both groups discontinued the therapy due to an AE.
The new approval of this medication is huge for this patient community. But Pfizer makes it clear the work is far from done. They speak of the importance of increased education, awareness, and ultimately, earlier diagnosis of ATTR-CM to improve patient outcomes.
You can read more about VYNDAQEL and the process toward its approval here.