AbbVie to submit upadacitinib to FDA after 5th trial win
- AbbVie aims to submit its experimental JAK inhibitor upadacitinib for approval in moderate-to-severe rheumatoid arthritis later this year after the oral drug met all its primary and second goals in its fifth Phase 3 study.
- A greater proportion of methotrexate-naive patients treated with either dose of AbbVie's drug achieved a measure of pain reduction known as ACR50 than those given methotrexate. At six months about half of patients in the upadacitinib arm were in clinical remission compared to only 18% on methotrexate.
- Importantly for drugs in this class, no new safety signal cropped up in the study, called SELECT-EARLY. Only one case of an adjudicated venous thromboembolic event, a key adverse event, occurred among the 631 patients treated with upadacitinib in the trial.
Just last week, Eli Lilly's Olumiant (baricitnib) became the newest JAK inhibitor to win U.S. approval, joining Pfizer's blockbuster Xeljanz (tofacitnib) and Incyte's Jakafi (ruxolitinib) on the market.
Its approval, though, came with major caveats. The Food and Drug Administration only OK'd a lower dose of the drug, which will carry a black box warning cautioning against the risk of thrombosis. Additionally, the approval only clears use of the drug in patients who have already tried anti-TNF drugs like Humira (adalimumab) or Enbrel (etanercept).
It's a fate that AbbVie and rival JAK developer Gilead Sciences hope to avoid in development of their respective experimental drugs.
"The critical question for investors will be whether upadacitinib can avoid a similar black box," wrote Leerink analyst Geoffrey Porges in a recent note to investors.
"Failure to secure a differentiated label over Olumiant would decrease expectations for the drug and open a significant opportunity for Gilead's filgotinib, while avoiding some of the class labeling would strengthen investor confidence in AbbVie’s ability to deliver on their ambitious $3 billion 2025 guidance for upadacitinib in rheumatoid arthritis ($6.5bn across multiple indications)," Porges said.
On that score, SELECT-EARLY offered further positive signs of upadacitinib's profile.
"Results suggest upadacitinib as a monotherapy has the potential to control rheumatoid arthritis and reduce the risk of permanent bone and joint damage for methotrexate-naïve patients," said Ronald van Vollenhoven, director of the Amsterdam Rheumatology and Immunology Center ARC, in a statement.
While methotrexate is a common first-line therapy, many people do not respond or cannot tolerate the drug. AbbVie's trial shows that treatment with upadacitinib led to higher proportions of patients achieving ACR20, ACR50 and ACR70, than methotrexate.
"Methotrexate is the universally accepted (and low priced) standard of care treatment for this indication and setting, but this data suggests that for some patients at least, its days might be numbered," Porges wrote.
A prior study, known as SELECT-COMPARE, also showed that upadacitinib beat out AbbVie's own Humira on all three ACR scores.
The data could have broader implications too.
"The results confirm the efficacy of the JAK class, their superiority over methotrexate, and reduce the safety concerns of this molecule at least regarding the risk of venous thromboembolic events (VTEs)," according to Porges.
Investors, though, will likely remain cautious about the drug's prospects until it is approved with a less restrictive label than Lilly's Olumiant.
- BioPharma Dive Lilly's JAK woes set the stage for AbbVie, Gilead to jump ahead
- BioPharma Dive Lilly's baricitinib gets FDA OK, but faces hurdles
Follow Suzanne Elvidge on Twitter