Prediction: AbbVie's Next Blockbuster Is Hiding in a Two-Drug Crohn's Combo

AbbVie (NYSE: ABBV) has already pulled off one of the great commercial pivot stories in pharmaceutical history. When Humira -- once pharma's top-selling drug -- lost patent exclusivity, the Chicago-based company leaned on Skyrizi and Rinvoq, which generated $17.5 billion and $8.3 billion respectively in 2025. Skyrizi alone exceeded $10 billion in revenue in the first half of 2026.

Most investors consider that reinvention story complete. It isn't. AbbVie may be building its next blockbuster -- and this one could eventually outperform its predecessor.

Image source: Getty Images.

A powerful combo

AbbVie's ABBV-466 pairs its blockbuster Skyrizi with a second antibody called trosunilimab, each targeting a different driver of Crohn's inflammation. In a Phase 2 clinical study, the combination put more patients into remission than either drug delivered on its own -- meeting the study's primary endpoint.

The numbers are striking. At week 12, 30.2% of patients treated with the combination reached endoscopic remission -- defined as the absence of visible inflammation in the gastrointestinal tract -- compared to 21.3% of those on Skyrizi and 18% of patients on trosunilimab. More importantly, the advantage widened as the trial progressed. At week 24, 40.5% in the ABBV-466 group reached endoscopic remission, compared to 22.4% of patients treated only with Skyrizi and 20% of those on trosunilimab monotherapy.

That's not a modest improvement over Skyrizi -- already the standard of care in Crohn's disease. It's nearly double the remission rate, and the gap widened over time, a pattern that typically signals a durable biological effect rather than a transient one.

The science behind the result makes intuitive sense. Skyrizi targets one key driver of Crohn's inflammation, but AbbVie's research showed that some patients were still experiencing flare-ups through a second, separate pathway that Skyrizi leaves untouched. Trosunilimab was added specifically to block that second pathway. The result is a combination that closes both doors simultaneously, applying the same logic that has made combination therapy the standard of care in cancer treatment.

Rates of serious adverse events were slightly higher for ABBV-466 at 10.4%, compared to 9.6% on Skyrizi monotherapy and 9% on trosunilimab alone. However, that's a modest difference that isn't unusual for a combination regimen and one that the clinical benefit appears to justify.

Adding to AbbVie's success story

Wall Street took notice immediately. The result led BMO (NYSE: BMO) Capital Markets to ask: "Sky is the limit?" BMO analysts said the early data for ABBV-466 "could chart a path for a more efficacious dual-targeting version of Skyrizi" and called the results "a positive for ABBV shares, potentially positioning the company with an efficacious follow-up molecule to Skyrizi in Crohn's."

BMO wasn't alone in its enthusiasm. RBC (NYSE: RY) Capital Markets analysts wrote that they see it "as a win for ABBV's lifecycle management with Skyrizi and for its next-gen agents in development, and reinforces our thesis that ABBV is building a durable moat in IBD through next-gen combo strategies."

ABBV-466 holds the potential to add to AbbVie's success story. The pharma stock is up almost 30% year-to-date. It has more than doubled over the past three years, handily beating the S&P 500 (SNPINDEX: ^GSPC). AbbVie's stock is also a favorite for income investors. The company is a member of the Dividend Kings, an elite group with dividend increase streaks of at least 50 consecutive years.

A prediction and a caveat

I predict that ABBV-466 is the beginning of AbbVie's next blockbuster story. I also think that this story is one that the market is not yet pricing into the stock.

There's a caveat to my prediction, though. ABBV-466 has only had Phase 2 results so far. A Phase 3 program and a multi-year path to potential approval still lie ahead. Investors buying AbbVie today on ABBV-466 are doing so well before the confirmatory evidence arrives.

That caveat aside, AbbVie has earned the benefit of the doubt on lifecycle management. When Humira's exclusivity ended, most analysts underestimated how completely Skyrizi and Rinvoq would fill the commercial gap. My prediction is that ABBV-466 tells that same story a second time.

Keith Speights has positions in AbbVie. The Motley Fool has positions in and recommends AbbVie. The Motley Fool has a disclosure policy.