Many companies are pursuing interchangeable status.
For the first time, biosimilar manufacturers this year are taking on the all-time reigning drug for revenues, Humira (adalimumab). Humira is an autoimmune drug that in peak years has garnered more than
$20 billion in global sales.
It is early innings in a game that will presumably last decades. It is both difficult and premature to assess whether the biosimilars will challenge Humira’s hegemony. As this issue went to press, eight of the nine FDA-approved Humira biosimilars had launched: Amgen’s Amjevita (adalimumab-atto), Boehringer Ingelheim’s Cyltezo (adalimumab-adbm), Organon/Samsung Bioepis’ Hadlima (adalimumab-bwwd), Biocon’s Hulio (adalimumab-fkjp), Sandoz’s Hyrimoz (adalimumab-adaz), Fresenius Kabi’s Idacio (adalimumab-aacf), Celltrion’s Yuflyma (adalimumab-aaty) and Coherus BioSciences Inc.’s Yusimry (adalimumab-aqvh). Pfizer’s Abrilada (adalimumab-afzb) is approved but hadn’t launched. If the FDA approves Teva/Alvotech’s AVT02, it may also be entering the fray.
In first-quarter earnings statements, AbbVie, Humira’s manufacturer, reported approximtely $2.9 billion in U.S. net revenues from Humira, which is a 26% drop from the first quarter of 2022. Meanwhile, Amgen reported a 52% rise in global Amjevita sales, which included the U.S. market. The relative amounts may be misleading, as the Amjevita sales don’t account for more than a fraction of the $1 billion decline in Humira’s market. Amgen attributed U.S. sales of Amjevita in part to inventory stocking by pharmacies — that is, buying product in anticipation of future need, not in response to existing demand.
For its part, AbbVie’s reported Humira $1 billion sales decline may be attributable in part to discounting and rebate strategies imposed to compete with lower prices for biosimilars, and not to major drops in volume of units. For example, Amgen is offering Amjevita at up to 55% below Humira’s list price of $6,922 per month. Buyers may also be holding off in anticipation of lower-priced biosimilars. Either way, a 26% drop in revenues is a sharp decline in the Humira sales in a very short period of time.
Biosimilars got off to a slow start in the U.S. However, the recent history has demonstrated that after a slow start, they have been capturing market share at ever-increasing rates. Biosimilars launched within the past three years have captured 75% market share on average from originator therapeutics, according to Amgen’s 2022 Biosimilars Trends Report, and reference drug prices have been dropping between 4% and 21% yearly when faced with biosimilar competition.
AbbVie saw this day coming and did not go gentle into that maelstrom. The company spent much of 2022 locking down deals with pharmacy benefit manufacturers (PBMs) and payers to ensure Humira would not lose too much ground too quickly in health plans and on formularies.
The company also worked hard to build demand for its two next-generation immunology drugs — Rinvoq (upadacitinib) and Skyrizi (risankizumab) — which saw U.S. sales increase 44.4% and 45.9%, respectively, in the first quarter of this year relative to 2022. AbbVie hopes these products will eventually fill the sales vacuum created by biosimilar competition for patients who are taking Humira.
“In summary, we are one-quarter into the U.S. biosimilar event for Humira and are managing the erosion well,” AbbVie CEO Richard A.Gonzalez assured investors in the company’s first quarter earnings conference call.
Cost Plus Drugs deal
Biosimilar manufacturers have long awaited this moment. Their biosimilars have been available in other markets around the world, and although many received FDA approvals years ago, AbbVie successfully kept them off the U.S. market through patent litigation and negotiations until now. However, now the gold rush is on, with as many as 10 biosimilars vying for a share of the U.S. Humira market, which measured $18.6 billion dollars in 2022. These contenders have also spent months negotiating in advance with PBMs and payers to open preliminary sales channels for their products.
Apparently, no holds are barred in this struggle. Coherus has a licensing agreement with AbbVie to sell Yusimry for no less than $955 for a month’s supply, but Mark Cuban Cost Plus Drug Company, a deep discounter, said it will sell Yusimry for $569.27. At this writing, Coherus and AbbVie were in litigation over the matter. The Cost Plus Drug deal also threatens to undermine AbbVie’s licensing arrangements with the many other companies launching Humira biosimilars this year.
Many biosimilar companies have jockeyed to enhance their product’s marketability through appellation of the “interchangeable” label, which takes basic biosimilar approval one step further with FDA certification that switching patients multiple times from Humira to the biosimilar and back again will not adversely affect outcomes.
The FDA does not intend the interchangeable label to be an indication of superior clinical efficacy or safety over a standard biosimilar approval. However, in recent surveys, a preponderance of physicians (60%) stated that they would feel more comfortable prescribing Humira interchangeables than biosimilars without that label, even though both kinds are approved largely on the basis of pharmacokinetic and pharmacodynamic evidence of high similarity to the originator drug, and clinical studies are increasingly viewed as a less-precise standard of evidence for determining biosimilarity to the originator product.
Doctors may simply be leaning conservatively toward what they perceive to be the most rigorously tested biosimilars, but the message picked up by many Humira biosimilar manufacturers and distributors is that they had better obtain interchangeable designations if they expect their products to sell.
Amjevita does not have an interchangeable designation, but Amgen is now pursuing one. Organon/Samsung Bioepis are in the same boat with Hadlima, as is Biocon with Hulio, Pfizer with Abrilada, Teva/Alvotech with AVT02 and Celltrion with Yuflyma. Alvotech was one of the few companies, if not the only one, that set out from the get-go with the intention of securing interchangeability with original FDA biosimilar approval. Many of the others have pursued this designation as an afterthought, which is why so many are launching with FDA interchangeable designations pending. As of this writing, among Humira biosimilars, only Cyltezo has an interchangeable designation.
The majority of Humira biosimilars are citrate-free, which means less pain at the injection site for patients. Manufacturers realized early on that this was an important distinction for patient and provider acceptance of their products. Cardinal Health surveys have shown that citrate-free
formulations are rated as very important by rheumatologists and gastroenterologists. Citrate-free formulations were a no-brainer for manufacturers, but interchangeability is less clear cut. In some cases, interchangeability allows pharmacists to share the decision of what brands of a particular drug are dispensed to patients — something many doctors initially resisted.
Tony Hagen is a medical, business and environmental editor and writer in Florence, New Jersey.