AbbVie Inc. is revving its engines with a deep pipeline of late-stage drug programs focused on immunology and cancer, as the company's best-selling arthritis therapy Humira enters its final full year without U.S. competition.

Humira, the best-selling prescription drug in the world in 2020, will face biosimilar competition in the U.S. from new versions rolling out almost every month in 2023. The lack of direct rivals helped the therapy pull in $17.33 billion of U.S. revenue for full year 2021, up 7.6% year over year. In international markets, where AbbVie has already encountered competition from biosimilar copycats of Humira, the medication saw revenue of $3.4 billion, down 9.6%.

The pharmaceutical giant expects a drop in overall revenue in 2023 and 2024 with these biosimilars entering the U.S. market, though CEO Richard Gonzalez said AbbVie's other prospects will begin to pick up the slack.

"I believe you'll see further erosion from '23 to '24 on the Humira business alone, but what we have described is we return to growth on the overall business," Gonzalez said on the company's fourth-quarter earnings call Feb. 2. "So you have to think about it from the perspective of this underlying growth engine that gets suppressed in '23 by the significant erosion that you see around Humira, both price and some volume."

Humira will see a sales erosion of about 45% in 2023, plus or minus 10%, Gonzalez said. With U.S. sales of the drug expected to grow 8% in 2022, a 45% drop in 2023 would amount to a loss of $8.4 billion.

To fill that void in the immunology business, AbbVie is looking to its newer drugs with different modalities to Humira's TNF blocking agent: the JAK inhibitor Rinvoq and the IL-23 inhibitor Skyrizi.

Rinvoq and Skyrizi brought in $1.66 billion and $2.94 billion, respectively, worldwide in 2021. The company expects combined global sales of more than $15 billion for the two drugs in 2025 as new indications are approved, AbbVie Chief Commercial Officer Jeffrey Stewart said on the call.

In addition to Rinvoq's current approved uses for patients with arthritis and eczema, AbbVie is conducting four late-stage studies for new indications, including Crohn's disease. Skyrizi is in a late-stage trial for ulcerative colitis.

Skyrizi and Rinvoq are "growing strong and will help make up for the Humira patent expiration next year," said Edward Jones analyst Ashtyn Evans.

Rinvoq's growth trajectory is likely to remain a "key focus" in 2022 as the drug's label expands, JP Morgan analyst Christopher Schott said in a Feb. 2 note.

In cancer, AbbVie has eight late-stage programs, including new indications for blockbusters Imbruvica — a partnership with Johnson & Johnson — and Venclexta.

Sales of Imbruvica, in particular, were weakened by the COVID-19 pandemic as well as competitive dynamics, including from Venclexta itself, executives said.

"The thing that was not ever anticipated in that guidance was the impact that COVID would have on the market and the reduction that we saw in the number of new patients, which was quite sizable," Gonzalez said.

AbbVie's fourth-quarter revenue of $14.89 billion was a 7.4% increase on the year-ago period but fell just short of analyst expectations of almost $15 billion. However, adjusted EPS rose 13% in the quarter to $3.31, ahead of consensus estimates of $3.29.

AbbVie's Botox pillar

Botox posted strong sales for AbbVie, which acquired the wrinkle reducer and therapeutic in its 2020 acquisition of Allergan. The therapy was a "clear bright spot" for the company, with sales beating analysts' expectations for the fourth quarter, JP Morgan's Schott said.

Botox brought in full-year global sales of $2.23 billion for cosmetic uses and $2.45 billion on the therapeutic side, for reported year-over-year growth of over 100% and 76%, respectively.

Although several competitors stand up against Botox in aesthetics, Gonzalez attributed the drug's monolithic position to ease of use and customer loyalty.

"It's a pretty impressive position that Botox has in the market — when you look at the brand equity that it has, when you look at the confidence that injectors have in using the product, they tend to describe it as the most forgiving of all the toxins that they have experience with," Gonzalez said.

To shore up the aesthetics business against incoming competition, AbbVie is conducting mid-stage trials for two new neurotoxins, BoNTE and OnabotA X. These products could help grow the market as both short-acting and long-acting options, the CEO said.

"I'm not overly concerned about what I see on the horizon," Gonzalez said. "We have the opportunity to build the market even larger with some of the next-generation toxins that we're working on, when we bring those to the marketplace. So I feel good about our position in toxins and in fillers as we move forward."