- AbbVie's investigational medicine for a bowel disorder is headed for late-stage testing after the company revealed positive topline results from a Phase 2 study.
- The CELEST trial tested upadacitinib against placebo as a treatment for patients with moderate-to-severe Crohn's disease (CD) who did not respond to at least two biologics prior to enrollment. The study evaluated five dosing regimens of the drug, ranging from 3 mg twice daily to 24 mg once daily, and found significantly more patients had no intestinal inflammation when they took at least 6 mg of the drug twice each day.
- Upadacitinib works by inhibiting proteins called Janus kinases (JAKs), which can cause autoimmune disorders and harmful inflammatory responses if they go haywire. AbbVie is also testing the drug for rheumatoid arthritis, ulcerative colitis and atopic dermatitis indications.
Correction: In a previous version of this article, we incorrectly characterized previous Xeljanz results.
These latest results may help AbbVie better position itself in the highly-competitive JAK-inhibitor space. While only three such drugs have been approved — Incyte's Jakafi (ruxolitinib), Pfizer's Xeljanz (tofacitinib) and Zoetis' Apoquel (oclacitinib), though the latter is for dogs — the global pipeline is more robust. Locking down multiple indications and dosings will be instrumental in a drug's ability to compete.
AbbVie's research program for upadacitinib reflects such a strategy. The drug is furthest along as a therapy for rheumatoid arthritis (RA), a market the company knows all too well thanks to Humira (adalimumab). Xeljanz is also approved for that indication.
The North Chicago, Ill.-based drugmaker will want to be careful, however, to not run into the same late-stage and regulatory problems its competitors have. For instance, Gilead reported in November results from the SIMPLIFY-1 and SIMPLIFY-2 Phase 3 studies showing its candidate momelotinib wasn't superior to Jakafi at treating myelofibrosis patients. And last month, the Food and Drug Administration rejected baricitinib, another Incyte drug that has been licensed to Eli Lilly.
Even Xeljanz has faced setbacks, with the monotherapy failing to beat out a combination therapy of Humira and methotrexate as a treatment for moderate-to-severe RA, while the combination with methotrexate only showed non-inferiority.
To that end, AbbVie will need to keep an eye on the safety of its drug.
The company said in a May 9 statement that upadacitinib's safety profile in CELEST was along the same lines as it was in rheumatoid arthritis trials, with side effects experienced more often in the experimental arms versus control arm. Though there wasn't evidence that adverse events were tied to dosing, there were more serious AEs in the 12 mg twice daily pool. Additionally, one patient died, though it was before taking AbbVie's medication.
Safety aside, moving upadacitinib into late-stage testing for an indication other than RA helps prevent all of AbbVie's eggs from ending up in the same basket.
Early results from CELEST showed strong efficacy across certain dosing arms. Patients receiving the 24 mg twice daily regimen, for example, had a 22% rate of endoscopic remission versus 0% among those taking placebo. Those on the 6 mg twice daily regimen also had a 27% rate of clinical remission — a slightly different measure that accounts for symptom alleviation — compared to 11% of the placebo population.
While the JAK-inhibitor space hasn't been a knockout, revenues are starting to rev up for approved products. Income from Xeljanz, for example, grew 27% in the first quarter to $250 million, according to Pfizer's most recent financial report, and almost ticked past blockbuster status last year, reaching $927 million.