It's not a well-known disease. But transthyretin amyloidosis cardiomyopathy, a rare condition affecting the heart, has become the target of a major drug development effort.
One medicine, from Pfizer, is approved and two others, from BridgeBio Pharma and Alnylam Pharmaceuticals, have succeeded in late-stage testing. Deciding which offers the greatest benefit has consumed analysts on Wall Street and top experts in the field. At stake is a market worth billions of dollars.
By Thanksgiving, the Food and Drug Administration is expected to decide on approval of BridgeBio's acoramidis, likely kicking off a new phase in the debate. The agency is also set to reach verdicts this quarter on important drugs from AstraZeneca, Vertex Pharmaceuticals, Bristol Myers Squibb and PTC Therapeutics. Here are five FDA decisions to watch:
BridgeBio’s acoramidis for transthyretin amyloidosis cardiomyopathy
Rarely do biotechnology companies rebound from lackluster Phase 3 trial results. But BridgeBio Pharma did exactly that with acoramidis in transthyretin amyloidosis cardiomyopathy.
Like Pfizer’s Vyndamax — the only available treatment and a multibillion-dollar seller — acoramidis is supposed to stop a protein implicated in the disease from misfolding. Preclinical data suggested it did so more effectively than Vyndamax, raising expectations it might be superior.
But BridgeBio had difficulty proving its case. In 2021, the drug missed the first of two main Phase 3 study goals when people who received a placebo performed better on a walking test than past results suggested. BridgeBio attributed that result, in part, to the better all-around care people with the disease now receive, which in turn means studies may have to run longer to detect a benefit.
AstraZeneca and Daiichi Sankyo’s dato-dxd for lung cancer
AstraZeneca and Daiichi Sankyo already have one breakout success in Enhertu, a drug the companies teamed up to develop and that has since changed how certain breast cancers are treated. Their chances at another, with a similar type of drug called datopotamab deruxtecan, could hinge on the outcome of an FDA review due to wrap up by Dec. 20.
Like Enhertu, dato-dxd is a targeted medicine known as an antibody-drug conjugate. And as with Enhertu, the partners hope to prove the drug can supplant chemotherapy in multiple cancer settings.
But Enhertu has succeeded in a variety of different clinical trials, in some cases producing dramatic benefits. Dato-dxd’s case to regulators is less straightforward.
AstraZeneca and Daiichi originally intended to bring the drug to market for all people whose non-small cell lung cancers express a protein, TROP2, that it targets. But while dato-dxd delayed tumor progression compared to chemotherapy, it didn’t meaningfully extend survival. It was later associated with a numerical, but not statistically significant improvement when the companies zeroed in on people with “nonsquamous” tumors, whom the partners expected to benefit the most.
AstraZeneca and Daiichi are now aiming for an approval in nonsquamous non-small cell lung tumors specifically. They’ve also been working to better identify responders to strengthen their case for a drug analysts have projected as a future blockbuster. But the survival findings “make us suspicious about a straight approval,” and could portend a delayed decision and advisory committee meeting, wrote Stifel analyst Eric Le Berrigaud in a research note last month. — Ben Fidler
Vertex’s ‘vanza triple’ for cystic fibrosis
Since 2012, Vertex Pharmaceuticals has won U.S. approvals for four cystic fibrosis medicines, making the lung condition manageable for thousands of people. Along the way, Vertex has turned into one of the industry's most valuable companies and is now worth $120 billion.
Vertex could expand its cystic fibrosis franchise further if the FDA decides to approve a combination treatment regimen known as "vanza triple." The FDA's deadline is Jan. 2, 2025, but the agency sometimes issues decisions early.
Like Vertex's current top-seller Trikafta, the vanza triple uses a compound called tezacaftor as its backbone. But the experimental drug replaces Trikafta's two other components with newer versions the company developed.
In testing, the vanza triple was found to be "non-inferior" to Trikafta on a measure of lung function commonly used in cystic fibrosis studies. It also proved superior to Trikafta on a secondary measure of sweat chloride, which is associated with the function of proteins that are mutated in people with the disease.
If approved, the vanza triple would offer patients the convenience of once-daily treatment, rather than the twice-daily dosing of Trikafta. And because it contains two newer compounds, Vertex would owe a lower rate of royalty payments than it does selling Trikafta.
Vertex could also enjoy longer patent protection on the vanza triple than for Trikafta, which is covered through 2037 in the U.S. — Ned Pagliarulo
PTC's Upstaza for AADC deficiency
Oftentimes, the FDA moves ahead of its regulatory counterparts around the world, approving drugs for the U.S. before they're available elsewhere.
That pattern flipped for a gene therapy PTC Therapeutics is developing for a rare genetic nervous system disorder known as AADC deficiency. In May 2022, the European Medicines Agency recommended the therapy, called Upstaza, for authorization, which the European Commission granted later that year.
But the regulatory process has taken longer in the U.S., where the FDA has gone back and forth with PTC over data intended to demonstrate the comparability of clinical and commercial drug product. The company could finally have its answer by Nov. 13, when the agency is set to decide on approval.
An approval would add Upstaza to a lengthening list of approved gene therapies for inherited diseases. But few have been commercial successes, putting pressure on biotech developers like PTC to prove they can profitably manufacture and sell the complex treatments. So far in Europe, PTC has not generated significant revenue from Upstaza. — Ned Pagliarulo
Bristol Myers’ subcutaneous Opdivo for solid tumors
Bristol Myers Squibb has earned tens of billions of dollars from its cancer immunotherapy Opdivo since an initial approval a decade ago. But that revenue could dry up within years, as the expiry of a key U.S. patent in 2028 will pave the way for biosimilar competitors. One way Bristol Myers could protect its profits is by bringing a new version of Opdivo to market. That could happen by Dec. 29, when the FDA is expected to issue a verdict on an Opdivo formulation administered via an under-the-skin injection.
Subcutaneous Opdivo is the product of a partnership between Bristol Myers and drug delivery specialist Halozyme. The alliance involves a Halozyme technology capable of making a more convenient version of Opdivo, which is typically given through an intravenous infusion lasting 30 minutes. Other drugmakers, among them Johnson & Johnson and Argenx, have worked with Halozyme for similar reasons. So has Roche, which got Halozyme’s help in making a subcutaneous version of the immunotherapy Tecentriq the FDA approved last month.
Bristol Myers and Merck & Co. are trying to catch up. Merck has a formulation of its drug Keytruda currently in late-stage testing, and initial study results could be coming soon, according to a federal database. Bristol Myers is closer, having already proven its under-the-skin Opdivo is statistically non-inferior to the marketed version. Approval would make the newer version available for all the tumors original Opdivo is cleared to treat.
Preserving Opdivo’s revenue is an essential part of Bristol Myers’ near-term strategy. The company’s top seller, the blood thinner Eliquis, will lose market exclusivity in 2026 and faces pricing pressure from Medicare. — Jonathan Gardner
