Heart drug Lipitor is the biggest-selling drug of all time. Perhaps no surprise to dedicated pharma-watchers, who know the statin med still racks up blockbuster-level sales despite years of generic competition.

It won't hold that crown for much longer, though. AbbVie's Humira is set to steal it away—and remain history's biggest-selling drug at least through 2024. Lifetime total by then? A whopping $240 billion.

That fact may not be all that surprising, either. But as generics continue to bite and biosimilars begin to rear their heads, the current set of all-stars is in for a shuffle over the next five years, according to estimates tallied by Evaluate Pharma.

Stalwarts will drop out, including the Sanofi and Bristol-Myers Squibb clotbuster Plavix. Newcomers will join—think Roche's cancer med Avastin and Celgene's Revlimid. And those drugs that remain will rearrange, leaving a roster that's familiar and new at the same time.

But credit where it's due: Since it went on sale in early 1997, Pfizer’s Lipitor had collected $164.43 billion through 2018.

AbbVie’s immunology superstar racked up $136.55 billion in sales since its 2003 launch. But even though the TNF-alpha inhibitor's sales have dropped by around 6% so far this year—thanks to ex-U.S. biosimilar competition—it's hefty enough to take that hit and still claim Lipitor’s title before 2024.

In fact, at the current rate, Humira could easily dethrone Lipitor next year. After all, it brought in nearly $20 billion worldwide last year, and U.S. sales growth is softening the EU biosimilars blow. Most importantly, AbbVie has fended off U.S. biosims till 2023, with the last holdout—Boehringer Ingelheim—inking a patent settlement in May.

And meanwhile, new psoriasis hopefuls, including AbbVie’s very own Skyrizi, have landed in Humira’s market, but the older drug is still set for $240.5 billion in lifetime sales by 2024, Evaluate estimates.

And Humira isn’t the only one that could enjoy a longer megablockbuster runway thanks to newly reinforced patent protection. Amgen’s rival TNF-alpha drug Enbrel recently fought off Novartis’ FDA-approved biosim Erelzi in court—a big win for Amgen and loss for Enbrel biosim hopefuls. The Amgen brand has made $108.2 billion since it came to market in 1998, and by 2024, it could be the industry’s third most successful drug with lifetime sales of $139.8 billion.

Roche’s trio of cancer cash cows Rituxan, Herceptin and Avastin might not be so lucky when it comes to biosim rivals. Like Humira, Rituxan and Herceptin have suffered quarterly losses to the level of 40% in the EU, where biosims have hit hard. But unlike Humira, their U.S. sales are now in danger, too.

Amgen and Allergan recently launched their Avastin biosim, Mvasi, and Herceptin biosim, Kanjinti, at a list discount of 15% to the original meds. And Teva and Celltrion are expected to launch their Rituxan copy, Truxima, in the U.S. this year.

That means Rituxan—with $136.1 billion in sales since launch—will drop from its current third place to fourth. But despite the competition, Herceptin ($114.9 billion) will move up a couple of notches to eighth place in 2024. And Avastin ($114.3 billion) will move onto the 2024 list in ninth place, as GlaxoSmithKline’s stomach acid drug Zantac joins Plavix on its way out of the ranks.

Another drug that will vault into the future best-seller list is Celgene’s myeloma therapy Revlimid. On the market for over a decade, Revlimid is still racking up big sales gains and adding new approvals to its label.

After showing it could improve survival, a combo of Revlimid, Takeda’s Velcade and corticosteroid dexamethasone recently won a nod for previously untreated multiple myeloma patients, helping push up Revlimid sales in the second quarter by 11%, to $2.73 billion. A pairing of Revlimid and Rituxan also recently nabbed a green light as a chemo-free regimen for previously treated follicular or marginal zone lymphomas.

Those new indications are probably not the only reason why Evaluate analysts are so optimistic about this blood cancer stalwart, though—or why Bristol-Myers can look forward to ongoing Revlimid cash after it closes its Celgene buyout.

The U.S. Patent and Trademark Office recently tossed out Dr. Reddy’s bid to nix three patents around Revlimid, effectively delaying the Indian firm’s generics launch to 2023. Revlimid could reach $123.6 billion in cumulative sales by 2024 to claim fifth on Evaluate’s 2024 ranking.

The other drugs on Evaluate's 2024 ranking include Amgen’s anemia drug Epogen, which is expected to drop from No. 5 to No.7. In the six years from 2019 to 2024, it will add just a bit less than $8 billion in sales to its lifetime total.

Meanwhile, as Johnson & Johnson's fight to hold Remicade's ground against biosims draws antitrust scrutiny, the TNF med is on its way to $117.2 billion by 2024, according to Evaluate's calculation. GSK respiratory giant Advair, now facing its first knockoff in Mylan’s Wixela Inhub, is expected to rise to $113.6 billion in 2024, up from $104.20 in 2018.