- AbbVie Inc.'s experimental arthritis drug upadacitinib succeeded in its fourth and largest-to-date Phase 3 study, beating out both placebo and the drugmaker's top-selling Humira in treating rheumatoid arthritis.
- Treatment with AbbVie's new drug, a JAK1 inhibitor, helped more patients achieve a 20% improvement in joint tenderness through 12 weeks and led to a higher proportion of clinical remission than either Humira or placebo, according to data released April 9 by AbbVie.
- Upadacitinib is one of several pipeline candidates the North Chicago, Illinois-based pharma hopes can make up for any lost revenues when Humira eventually faces biosimilar competition. The trial success bolsters AbbVie's case and offers a ray of good news after a stinging clinical setback last month.
AbbVie's Humira (adalimumab) is the most successful member of a class of drugs known as TNF inhibitors, used as a front-line treatment in a wide range of inflammatory conditions. Ever-rising sales of Humira have earned AbbVie nearly $93 billion since 2013, when the company split off from Abbott Laboratories.
That market dominance has also sparked investors worries of the hard landing AbbVie faces when Humira eventually faces cheaper competition from copycat biologics. In response, AbbVie has bulked up in oncology and pushed forward development of novel anti-inflammatories to fuel future growth in a post-Humira world. (Although biosimilar rivals aren't expected to reach the U.S. market until after 2022.)
The drugmaker predicts upadacitinib and another drug called rizankizumab to pull in $6.5 billion and $5 billion in annual sales by 2025, respectively. Analysts from Cowen are less bullish, predicting sales of $2.6 billion and $2.3 billion for each respective drug by 2024. Still, most see the two experimental treatments as core to AbbVie's future plans.
Three other studies of upadactinib have read out positive results so far. The data from AbbVie's latest trial, called SELECT-COMPARE, further bolster the drug's profile. The study enrolled over 1,600 RA patients on stable background treatment with methotrexate but had an inadequate response.
On efficacy, upadacitinib demonstrated superior easing versus both placebo and Humira of the joint tenderness and swelling characteristic of RA.
Efficacy results at week 12 from SELECT-COMPARE
|Upadacitinib (n=651)||Humira (n=327)||Placebo (n=651)|
|ACR20 (primary endpoint)||71%||63%||36%|
SOURCE: AbbVie press release dated April 9
Importantly, results also showed the rate of venous thromboembolic events — a key safety concern for upadicitinib — among treated patients to be comparable to the rate seen in the placebo arm, and within the range of the known background rate in rheumatoid arthritis (RA).
Through six and a half months, serious adverse events were reported in 3.7% of patients given upadacitinib, 4.3% of those on Humira and 2.9% among placebo patients. One patient on upadacitinib experienced deep vein thrombosis and another had a pulmonary embolism, compared to three cases of pulmonary embolism in the Humira arm and one on placebo.
"The new data from SELECT-COMPARE should add clarity to upadacitinib's safety, but will need to be corroborated by the two remaining [Phase 3] trials that have yet to report results," wrote Cowen analyst Steve Scala in a April 9 note.
Results also lessen the risk of a major clinical setback for upadacitinib, potentially given more confidence after some signs of shakiness from the biopharma.
"After the recent failure of Rova-T in third-line small cell lung cancer, and the related drop in AbbVie's stock value of [greater than] 20%, the risk of a subsequent pipeline failure now also appears substantially reduced," said Leerink equity analyst Geoffrey Porges, in a April 9 note to investors.
AbbVie plans to submit upadacitinib for approval later this year following results from a fifth study comparing the drug to methotrexate in methotrexate-naive patients. Given how important the drug is for AbbVie, further strong results there would likely provide a lift to the drugmaker.