The Disease That Wasn't Rare After All

For decades, doctors were taught this was a rare disease, a slow stiffening of the heart called ATTR amyloidosis, the kind of case most cardiologists figured they'd never see. So they didn't look for it. The scan that could find it without cutting into the heart sat mostly unused in the nuclear-medicine department. Then Pfizer got a pill approved in May 2019, and the "rare" disease started turning up in elderly men with heart failure all over the country. The biology had not changed; what changed was that doctors finally had a reason to look.

How Common Is ATTR Cardiac Amyloidosis?

The wild-type form of ATTR amyloidosis (once called "senile systemic amyloidosis") has no genetic cause. It is simply age. A liver protein called transthyretin, normally a stable four-part clump, slowly comes apart over the years, misfolds, and piles up as stiff deposits, mostly in the heart, where they turn the muscle rigid and cause heart failure (the stiff-heart kind doctors call HFpEF). It hits older men almost exclusively: about 90% of patients are male, most found in their 70s and 80s.

"Rare" was the wrong word; "overlooked" is closer. Look at the autopsy and screening numbers. About 25% of hearts in people over 80 carry these deposits, whether or not the person ever had symptoms. In autopsies of people over 75 who had heart failure, 14 to 32% show cardiac amyloid, mostly ATTR. And when you actually scan older heart-failure patients with thickened hearts, about 13% have it. The US has millions of such patients, so even the low end points to a hidden group in the hundreds of thousands. It's also deadly: untreated, it gives a median survival of about 3.5 years. But that average hides a lot: caught early, patients live around 66 months; caught late, about 20. For all that framing, it was a common cause of heart failure in older men that doctors were trained not to see. (One inherited version, V122I, carried by an estimated 3-4% of African Americans, was being missed just as badly.)

Diagnosing ATTR Amyloidosis Without a Biopsy: The PYP Scan

The tools to find it showed up years before anyone used them. In 2005, Perugini and colleagues, writing in JACC, noticed something: an ordinary bone-scan tracer, the kind used to image the skeleton, lights up the heart in ATTR amyloidosis, but not in the other main type (AL, or light-chain). They built a simple 0-to-3 "Perugini grade" still used today. Then in 2016, Gillmore and colleagues published the study that should have changed everything. In 1,217 patients, a strong scan (grade 2-3) plus a clean blood and urine test, with no stray antibody protein, identified ATTR correctly 100% of the time, and the scan alone caught more than 99% of cases. For most patients, that meant no heart biopsy at all.

And then, for most of a decade, the scan sat mostly unused. Cardiac ATTR was diagnosed a little more each year as awareness grew, but it stayed badly under-recognized, nowhere near its true scale, and every reason traced back to one fact: there was nothing to offer the patient. With no treatment, there was no reason to scan. Doctors were still taught the disease was rare, so it never made the list of things to check. A heart biopsy felt like a lot to put someone through for a condition you couldn't treat. And the scan itself sat in the nuclear-medicine department, a test cardiologists just weren't ordering.

Why Did Pfizer Develop a Drug for a "Rare" Disease?

Here's the part the timeline hides: the drug wasn't built for the common, hidden heart disease at all. It got to market through a much rarer door. Tafamidis started in Jeffery Kelly's lab at Scripps as a small molecule meant to hold that transthyretin clump together so it couldn't fall apart. Kelly spun the work out into a company, FoldRx, in 2003 with the biologist Susan Lindquist, and its first target was not the heart. It was hereditary ATTR polyneuropathy (ATTR-FAP), a rare inherited nerve disease that runs in families in Portugal, Sweden, and Japan, where the only prior option was a liver transplant.

That's a classic rare-disease bet: a small, clearly-defined group of patients with a terrible disease and nothing to treat it. It's exactly how Pfizer described buying FoldRx in 2010, calling tafamidis a first non-surgical option for "underserved" patients and slotting it into its rare-disease business. (Pfizer never said what it paid.) The drug got its first approval anywhere in Europe, in November 2011, for the nerve disease, and as the first medicine ever approved for any amyloid disease. The US turned that filing down: the one nerve-disease trial had missed its main goals once the patients who left to get liver transplants were counted as failures, and the FDA wanted a second study Pfizer never ran. So tafamidis had no American approval at all until the heart version arrived.

The heart was a second, later bet. Tafamidis was already an approved rare-disease drug in Europe when Pfizer aimed it at the much bigger group of heart patients. That's the move that carried a rare-disease drug into a common, hidden disease, and it is where the diagnosis story really starts.

Tafamidis (Vyndaqel): The First FDA-Approved ATTR-CM Treatment

On May 3, 2019, the FDA approved tafamidis (Pfizer's Vyndaqel and Vyndamax) for the heart form, ATTR-CM. It was the first drug that actually slowed the disease instead of just easing symptoms. It works by holding the transthyretin clump together so it can't fall apart and form deposits. The approval came from one trial, ATTR-ACT (441 patients, 30 months): 29.5% of patients on tafamidis died, versus 42.9% on placebo, about a 30% lower risk of death. Vyndamax is one capsule a day (Vyndaqel, the original formulation used in the trial, is four).

Now there was a prescription to write, and ordering the scan finally led somewhere. The test hadn't gotten any better since 2016; what changed was that a positive result now mattered.

Why ATTR-CM Diagnoses Surged After 2019

You can see the change in the numbers. About four out of five patients now on treatment were diagnosed without a biopsy, using a test that has existed since 2005. And the wait got shorter: patients who came through before the drug was widely available waited a median of 6.2 months for a diagnosis; after approval, 2.4 (the table below has the full picture). That matters more than it sounds. Since survival tracks so closely with how advanced the disease is at diagnosis, catching it earlier, and in these cohorts starting treatment roughly a year sooner, is very likely to buy patients time.

The drug created the diagnosis, not the disease

It's worth being exact here, because the easy version of the claim is wrong. The drug did not create the disease. Wild-type ATTR was already in a quarter of 85-year-old hearts long before tafamidis existed; the deposits don't care whether a drug is on the market. What the drug created was the diagnosis: a reason to look, plus a proven way to confirm it without a biopsy.

And this wasn't one person's breakthrough. Perugini showed a scan could spot the disease (2005); Gillmore turned that scan into a diagnosis doctors could trust (2016); and the heart drug that finally gave them a reason to use it came out of Mathew Maurer's ATTR-ACT trial (2019). Three separate steps, years apart, and it was the drug that connected them.

ATTR Amyloidosis Treatments: Stabilizers, siRNA, and CRISPR

Once the pool of diagnosed patients started growing, the rest of the field moved in. Four different kinds of drug now go after the same protein, the same pattern you see with PCSK9, where an antibody, an RNA drug, and gene editing all chase one target.

A second pill, acoramidis (BridgeBio's Attruby), works the same stabilizing way and was approved in November 2024 after cutting heart deaths and hospitalizations by 42%, priced about level with Vyndamax, a competitor rather than the center of this story. The RNA drugs took a longer road. Patisiran was the first RNAi drug the FDA ever approved (2018) but was turned down for the heart in 2023; its successor vutrisiran, a shot once every three months, was approved for ATTR-CM in March 2025, the first drug cleared for both the heart and nerve forms. That reversal came down to how the two trials were built rather than to the molecule, a story told in full in Same Mechanism, Different Trial. Eplontersen treats the inherited nerve disease with a monthly self-injection; in July 2026 its ATTR-CM trial, CARDIO-TTRansform, the largest yet at 1,432 patients, missed its primary endpoint (a prespecified monotherapy subgroup did benefit; full data at ESC in August). And NTLA-2001 is a one-time CRISPR infusion that edits the gene inside the body, which would make it the first of its kind approved (unlike Casgevy, which edits cells outside it). It comes with a live safety story: after a patient in the ATTR-CM trial was hospitalized with severe (Grade 4) liver injury, the FDA paused both late-stage trials in late 2025; that patient later died. The agency lifted the holds and let both trials restart in early 2026 with tighter liver monitoring and new exclusion criteria. For now it remains an unproven bet.

Why Tafamidis Still Leads as ATTR-CM Competition Grows

Six years on, Pfizer still points to new patients being found as a reason the drug keeps growing, because the wave of diagnoses has not crested yet. And the franchise stays strong even as rivals pile in, because every new drug grows the same pool. Acoramidis, vutrisiran, and whatever comes next all need a diagnosed patient, and each one gives doctors one more reason to order the scan. The diagnosed patients are the real prize, and tafamidis, the drug that created them, leads the market.