AbbVie's stock and next megablockbuster take hits following new JAK warnings from FDA
While the FDA’s new warnings on JAK inhibitors are based on a review of a Pfizer trial, it’s AbbVie that may be hurt the most.
AbbVie’s stock fell by about 10% at one point Wednesday as its prized JAK inhibitor Rinvoq, once forecast to haul in $8 billion annually by 2025, was looped into new class-wide FDA warnings, which include risks of serious heart-related events, cancer, blood clots and death.
The review from the FDA follows Pfizer’s announcement in January that its six-year post-marketing trial for its JAK inhibitor Xeljanz, known as ORAL Surveillance, had failed. Across 4,362 patients, those who received either a low or high dose of Xeljanz experienced more major cardiovascular events — such as stroke and heart attack — than those on comparator TNF drugs Humira or Enbrel. They also had higher rates of cancer with Pfizer failing to hit non-inferiority on both primary endpoints.
First approved in 2019 for rheumatoid arthritis, Rinvoq brought in $731 million in 2020 sales.
While Rinvoq has not been studied in trials similar to the large safety clinical trial that the FDA reviewed for Pfizer’s Xeljanz, the agency still said that because they share the same mechanisms of action the FDA considers these drugs may have similar risks as seen in the Xeljanz safety trial. Wall Street analysts took issue with the extrapolation, pointing to what other regulators have done.
Rinvoq is also still under FDA review in atopic dermatitis, psoriatic arthritis and ankylosing spondylitis, and those decisions may be coming soon as the FDA postponed all of its reviews of JAK sNDAs until this review of the Xeljanz trial finished.
SVB Leerink analyst Geoffrey Porges wrote in a note to investors Wednesday:
Interestingly, outside the US, other regulators have neither imposed these restrictions, nor imposed such onerous safety language, nor have they treated all the drugs in the class equally with respect to safety. In our discussions with investors the updated safety language seemed to be the most likely outcome, but we and most investors had not anticipated the restriction to post-TNF patients (even though that is how Rinvoq and other JAKs are already being used in the US due to step-edit policies and formulary restrictions). The FDA’s statements do not offer any insight about whether the current reviews of the Rinvoq sNDAs for psoriatic arthritis, ankylosing spondylitis, and atopic dermatitis will be affected by this decision, or whether Pfizer’s abrocitinib can still be approved in atopic dermatitis. We tend to believe that the new indications will be approved, but with the caveats imposed by today’s overall regulatory action but this is highly uncertain.
Porges previously estimated that losing any one of these Rinvoq indications could pose a $500 million to $1.5 billion hit to the company’s long-term revenue expectations.
AbbVie did not respond to a request for comment on the new FDA warnings.
Overall, Porges said Rinvoq’s potential “is almost certainly reduced in the USA, by this labeling. However, it still seems feasible that the product can get to the $3.5-4.5bn in US sales required to support the company’s long term guidance of $8bn in peak sales.”
The biggest issue with the FDA’s actions today, Porges added, “is not the safety disclosure, but instead the restriction to second-or later-line treatment. AbbVie certainly contemplated moving Rinvoq into the first-line setting in RA, and also in new indications such as PsA, AS, AD and even IBD. Those first-line indications are now off the table, at least for the foreseeable future.”