Can Madrigal Pharmaceutical’s new patent protect Rezdiffra until 2044?
Zachary Silbersher
On July 16, Madrigal Pharmaceuticals announced that it had secured a new patent extending that may protect its drug, Rezdiffra, for almost another 20 years. The company announced that the Patent Office had issued a Notice of Allowance for a pending patent application. The press release indicated that the patent will include “claims directed to Rezdiffra’s commercial weight-threshold dosing regimen as prescribed in the FDA-approved label.” Is this patent strong enough to protect the drug from generics until 2044?
The company’s stock jumped on the news. The rally is likely a response to the Rezdiffra’s existing patent landscape. The Orange Book currently lists five patents covering Rezdiffra, but they will all expire by 2033. That is only four more years of patent protection after the drug’s NCE exclusivity expiration in 2029. The new patent could therefore protect the drug from generics for more than another decade.
All of this begs two questions—What is the patent? And how strong is it?
The press release indicates that the patent reads upon the label for Rezdiffra. In particular, it reads upon the weight-threshold dosing regimen. Rezdiffra’s label indicates that the drug has a recommended dosage of 80 mg for patients weighing less than 100 kg and 100 mg for patients weighing more than 100 kg. The patent likely covers these limitations. If so, then there is a high likelihood that the patent will be infringed by generics because they are compelled to copy Rezdiffra’s label.
Infringement, however, is just half of a patent’s strength. That means that the ultimate strength of the patent likely rests upon how likely it can stand up against invalidity challenges. When generics file ANDAs, and they are sued under the Hatch-Waxman Act, they will seek to invalidate the patent. There are a few things we can glean about the strength of the patent’s validity from the available information.
Patents typically expire 20 years from the date of the U.S. application. If Madrigal’s new patent expires in 2044, that suggests the patent application was filed in 2024. That means this is a very recent patent application. In order for the resulting patent to have such a long lifespan, i.e., it will not expire until 2044, then it must be based upon a parent application filed in 2024. It cannot be a continuation or divisional application with an earlier filing date.
This is borne out by a study published in October 2024. That study included a post-hoc analysis performed upon Rezdiffra’s Phase III trial (MAESTRO-NASH (NCT03900429)). The study concluded that the “only variable found to determine exposure to resmetirom among patients with MASH was body weight.” One doctor commented that the data provides reassurance that the body-weight dosing thresholds prescribed by the FDA are appropriate.
In other words, Madrigal ran a Phase III trial that administered both 80 mg and 100 mg to patients. The company then conducted a post-hoc analysis that looked at data from that Phase III study and concluded that 100 mg was more effective than 80 mg in patients with higher baseline body weight and BMI. The study also concluded that there was no observed difference in efficacy in dosage with patients with lower baselines body weight and BMI.
Madrigal then took that study and quickly filed a patent application. That application sailed through prosecution and was allowed very quickly. Patent applications can typically take 2 to 5 years to be granted. Here, the application appears to have been granted in less than a year. Madrigal likely filed for some form of expedited review, but even so, this does not appear to be a patent application that was dragged through multiple rejections before allowance.
Yet, all of this begs the question why Madgrigal’s Phase III trial was itself not prior art to the patent. The Phase III trial has itself been public for years. Madrigal announced the trial in 2019 and announced positive top-line results from the trial in 2022. Both of those announcements indicated that patients were receiving 80 mg and 100 mg dosages. Prior administration of those dosages, along with data of the enrolled patient body weights and BMI, were likely available. Either as anticipatory prior art or as prior use, Madrigal’s trial from 2019 itself seems like it should have acted as prior art against Madrigal’s patent regarding body weight dosing threshholds that was filed only in 2024.
To get around this, Madrigal likely argued to the Patent Office that the results of its post-hoc analysis in 2024 was unexpected. In other words, Madrigal likely told the Patent Office that doctors did not previously expect that the 100 mg dosage would be more effective for patients who weighed more. That question is likely at the heart of whether Madrigal’s new patent will stand up to invalidity challenges from generics in the future.
But was it really unexpected? For instance, Madrigal’s post-hoc analysis apparently showed that: “Pharmacokinetic modeling indicated that patients with a higher exposure to resmetirom showed a higher rate of sex hormone-binding globulin (SHBG) response (>120% increase in SHBG) and also a higher rate of MRI-PDFF response (>30% reduction in MRI-PDFF).” Whether or not that finding was unexpected or surprising is a fairly technical scientific question. That’s the question that will likely be at the heart of future invalidity challenges to this patent.
If Madrigal really did make an argument for patentability based upon unexpected results, it probably submitted data and affidavit expert opinion to support it. But patent examination is an ex parte proceeding. There is no counterparty submitting contrary data or contradictory expert opinions to rebut Madrigal’s arguments about what doctors knew, what they expected or what they believed to surprising.
Yet, during future litigation against generics, all of that data and expert opinion will come out in spades for both sides. Madrigal’s arguments to the Patent Office will be stress-tested in a manner they weren’t during examination of the patent. Investors can likely do their own analysis right now to determine whether Madrigal’s claim that it was surprising that a higher dosage of resmetirom worked better in patients with greater body weight. That scientific analysis will better inform whether generics for Rezdiffra will be barred for nearly another two decades.