Pfizer enters Alnylam, Ionis' TTR turf with early approval for cardiomyopathy drug, carrying a $225K price tag
Pfizer is set to pull its weight in transthyretin-mediated amyloidosis, a field that has so far been Alnylam and Ionis’ turf.
Transthyretin (TTR) is a relatively abundant protein in the blood, which transports thyroxine and retinol. But it can become unstable and misfold — due to a genetic mutation or environmental factors — sparking an accumulation of toxic amyloid aggregates in the heart or peripheral nerves.
On Monday, the big US drugmaker $PFE said the FDA had approved two oral formulations of its transthyretin-stabilizer tafamidis — Vyndaqel (80 mg, taken as four 20mg capsules) and Vyndamax (61 mg, taken as a once-daily single capsule) — to treat cardiomyopathy of wild-type or hereditary transthyretin-mediated amyloidosis (ATTR-CM) in adults, to reduce related hospitalization and death.
The drug has been touted by Pfizer executives as a potential blockbuster. Last year, the company followed up positive top-line results with data that indicated tafamidis spurred a 30% drop in mortality risk along with a 32% reduction in the risk of CV-related hospitalization.
Credit Suisse’s Vamil Divan estimated peak sales of $2 billion for tafamidis, but sees the “potential for the product to be significantly larger than that if Pfizer is able to commercialize it successfully.”
Vyndaqel comprises of tafamidis meglumine, while Vyndamax is made from tafamidis free acid — “both these doses are bioequivalent (in fact, the label specifically mentions that every 20 mg of tafamidis meglumine is equivalent to 12.2 mg of tafamidis free acid),” Evercore ISI’s Umer Raffat wrote in a note. Price has been set at $225,000/year, he noted.
However, Phase III data has shown similar efficacy at 20 mg and 80 mg, so a patient should be theoretically able to take the smaller dose (with a $55,000 price tag) effectively — but, “it is my understanding that Pfizer will phase out the 80 mg (which is 4 pills of 20 mg) later in the year. This will prevent this from happening,” he added.
RNAi drugmaker Alnylam $ALNY makes Onpattro, which is designed to treat the polyneuropathy caused by hereditary transthyretin-mediated amyloidosis (hATTR amyloidosis). Ionis’ $IONS/Akcea’s $AKCA Tegsedi is approved for the same patient population. Each treatment costs about $450,000 a year.
Analysts have suggested that even though the Pfizer drug and two existing products are targeting different indications — there will still be competition — since many patients with cardiomyopathy tend to also have polyneuropathy and vice versa.
The earlier-than-expected approval specifically calls out being able to reduce mortality and CV-related hospitalizations, making it likely tafamidis will own the segment of the hATTR market that’s defined by pure cardiomyopathy, Stifel analysts wrote in a note.
The mixed polyneuropathy/cardiomyopathy patients are more likely to be a battle ground area where one can certainly make a case for both tafamidis and knockdown drugs at the same time…But among patients with true debilitating polyneuropathy, we expect Onpattro/Tegsedi to be preferred over tafamidis where for the latter, the polyneuropathy data are fairly equivocal/modest in our view. In the near to mid-term, we assume knockdown drugs can capture 35% of mixed phenotype in 2021. We also believe the premium price of Tafamidis at over $225k is a marginal positive for ALNY/AKCA/IONS; while you never know for sure what payors might do to restrict access, if Tafamidis had been priced at a much lower level, say below $100k, it could’ve raised concerns that insurers would position this drug as first line in hATTR across the board, regardless of phenotype.
The big hurdle in front of Pfizer is now getting ATTR-CM diagnosed properly — roughly 100,000 Americans suffer from the disease, but only 1% to 2% have been diagnosed, according to the drugmaker. Often ATTR-CM is diagnosed only after symptoms have become severe, and once diagnosed, the median life expectancy in patients — depending on the sub-type — is approximately 2 to 3.5 years, the company added.
“Pfizer has highlighted this is a market that will need to be build out…we understand that ~400-450 patients are already in the expanded access program. This likely means that 2020 consensus of $250 million is likely achievable,” Raffat noted.
Vyndaqel has been approved for transthyretin amyloid polyneuropathy in the European Union since 2011, and is now approved for the indication in 40 countries, excluding the US where it was rejected for the indication in 2012.
Bridgebio-backed Eidos Therapeutics $EIDX is also developing an oral treatment for TTR amyloidosis.
