Adalimumab biosimilar (Fujifilm Kyowa Kirin)

With the launch of its biosimilar of Abbvie's Humira, Biocon Biologics doesn’t want to blindly chase a larger share of the market, its CEO said. The biosimilar fracas targeting AbbVie’s megablockbuster Humira is taking shape. But to Biocon Biologics CEO Shreehas Tambe, the battle doesn’t solely revolve around market share. Humira, also known as adalimumab, generated $18.6 billion in annual U.S. sales before losing exclusivity early 2023. “It’s a very large opportunity, and even a small market share is a large value,” Tambe said in an interview. Before launching its biosimilar of Humira in July, Biocon Biologics had products on the U.S. market referencing Roche’s Herceptin, Amgen’s Neulasta and Sanofi’s Lantus. Each of them has captured at least 10% of total market share in their respective territories. With the Humira biosimilar launch, it’s unclear whether Biocon can reach that level of market share, the CEO acknowledged. And the company doesn’t want to blindly go after more share by offering steeper discounts. “The unfortunate math on market share is it’s disproportional to the average sales price,” Tambe added. “That’s why we’re […] very cautious in gaining market share. It’s always been a profitable growth that we’ve focused on.” Eight other biosimilar players have already introduced their Humira copycats or are prepared to launch this year. Branded drugmaker AbbVie is also fighting hard—so far successfully—to retain share for the originator. Adding to the complexity of the competition is “white labeling,” where retailers sell a drugmaker’s product under their own branding. In August, CVS Health launched Cordavis, a custom-built subsidiary to commercialize biosimilars. The division has contracted with Sandoz to market its adalimumab biosimilar, called Hyrimoz. Meanwhile, CVS Caremark is a top pharmacy benefit manager with a formulary that dictates which drugs insurers cover. Like it did with its Lantus biosimilars, Biocon rolled out two versions of adalimumab, one branded, called Hulio, and one unbranded. With a high list price, Hulio caters to payers who seek out high rebates. The low-price option targets group procurement organizations such as hospital systems. Between Biocon’s Lantus copies, the branded version, Semglee, has slightly more market share after the FDA doled out a first-of-a-kind interchangeability status, which allows pharmacists to switch the originator for the biosimilar at the counter. By comparison, Tambe suggested it will take time to gain more visibility into the market dynamics of Humira. Over the long run, Tambe said three factors will determine Hulio’ success: the right pricing strategy, reliable global supply and the delivery device. While some devices administer adalimumab in three steps, Hulio only takes two clicks. Tambe attributed its drug’s strong demand in Europe to the easy-to-use injector. As of June, Biocon’s adalimumab biosimilar has gained market share of over 18% and 10% in Germany and France, respectively. Biocon Biologics gained its commercialization capabilities by buying the biosim franchise of its former partner Viatris. The deal allows Biocon to build a fully integrated biosimilars business, Biocon’s founder and executive chairperson, Kiran Mazumdar-Shaw, said during the interview. The company doubled down on biosimilars even as large pharmas exited the space. But Mazumdar-Shaw argued that the shift stems from differing business models and that biosimilars remain an attractive field for a low-cost company like Biocon. “Many of the Big Pharma started to use biosimilars as a buffer because their pipelines were not delivering for them,” she said, noting that the companies reversed course “the moment they started getting their pipelines fixed.” Biocon’s biosimilar franchise has suffered a few recent manufacturing-related setbacks. Shortfalls spotted during FDA’s inspections at Biocon Biologics’ facilities in Malaysia and Bangalore led to rejections for the company’s biosimilar versions of Novo Nordisk’s NovoLog and Roche’s Avastin, respectively, earlier this year. For the insulin aspart product, the FDA has accepted Biocon’s correction plan with a new target decision date in October. The company has also submitted a plan for the Bangalore application and is now awaiting a response from the agency, Mazumdar-Shaw said. “None of our citations […] have any systemic issues,” she stressed, noting that some problems are caused by different interpretations of the FDA’s guidelines.

Pictured: Group of pills/Courtesy, iStock, Sergii Batechenkov The recent flood of Humira biosimilars to enter the market highlights the uncertainty that surrounds generic competition for biologics following the introduction of the Inflation Reduction Act. On July 1 and 3, seven biosimilars entered the U.S. market to challenge Humira, joining Amgen’s Amjevita (adalimumab-atto), which hit the market in January. This flood of generic competition adds insult to injury to AbbVie’s blockbuster arthritis drug, which was penalized under the Inflation Reduction Act (IRA) for its price hike, affecting price and hence competition. L.E.K. Consulting Managing Director Alex Guth told BioSpace that the competition from biosimilars “has a substantial negative impact on net pricing potential for existing biologics, including Humira.” Penalties and price negotiations imposed by the IRA burden biologics even further, he added. The legislation was signed into law in August 2022, and the Centers for Medicare and Medicaid Services (CMS) has already penalized 70 drugs and biologics so far. In June, the federal government flagged 43 drugs, including Humira, whose prices have risen faster than the rate of inflation and are thus required to pay a penalty in the form of a rebate to Medicare under the Medicare Prescription Drug Inflation Rebate Program portion of the IRA. The rebate will be the difference between what the price increase would have been if the manufacturer had stuck with the inflation rate for its increase and the actual increase of the drug or biologic. For Humira, that amounts to a reduction of 19.72% from what its prices would have otherwise been. The Biden administration said it intends to invoice these manufacturers by the fall of 2025. Meanwhile, beginning in April, the 20% coinsurance that consumers are charged began to be calculated based on a price increase commensurate with the inflation rate. Until September 30, 2023, Medicare patients may see coinsurance amounts for these drugs reduced by $1 to $449 versus what they would have received before the IRA. The price penalty combined with the entry of biosimilars adds pressure to price competition. Humira biosimilar developers have adopted different pricing strategies. Amgen and Biocon Biologics have said they would sell their products at two prices, with the first at a small discount relative to Humira’s new adjusted price of about $7,299 for two subcutaneous kits, or about $84,000 for a year’s supply and the second at an even steeper discount. Biocon said its second price would be 85% lower than Humira’s—about $12,500 each year. Humira is likely a cautionary tale, experts say. CMS will issue a new list of drugs and biologics that will be subject to rebates based on the rate of inflation on a quarterly basis, and which ones are subjected to rebates could change each quarter as the rate of inflation changes. This volatility is expected to perpetuate uncertainty in the biosimilars market. In addition, the drug price negotiation portion of the IRA further complicates the issue without a clear answer as to whether the legislation will encourage or discourage the development of biosimilar drugs. Overview of Humira Biosimilars The first Humira biosimilar to enter the market was Amgen’s Amjevita (adalimumab-atto) in January. Earlier this month, seven more joined the competition: Fresenius Kabi’s Idacio (adalimumab-aacf), Biocon Biologics Ltd’s Hulio (adalimumab-fkjp), Boehringer Ingelheim’s Cyltezo (adalimumab-adbm), Organon & Co. and Samsung Bioepis Co., Ltd.’s’ Hadlima (adalimumab-bwwd), Sandoz’s Hyrimoz (adalimumab-adaz), Celltrion USA’s Yuflyma (adalimumab-aaty) and Coherus BioSciences, Inc.’s Yusimry (adalimumab-aqvh). The only Humira biosimilar that has received interchangeability designation, which allows pharmacists to substitute a biosimilar at the point of dispensing without prior authorization from the prescriber, is Cyltezo. How Will Price Negotiation Affect Biosimilars? The industry trade lobbying group Pharmaceutical Research and Manufacturers of America (PhRMA) issued a report in June that examines these issues. PhRMA, along with Merck, BMS and others, has sued the U.S. government, challenging the constitutionality of the IRA’s drug price negotiation program. “Under the IRA, biosimilar manufacturers are not able to predict, with any accuracy, which biologics will be subject to price setting, creating significant uncertainty regarding whether there will be an opportunity to recoup the investments required to develop a biosimilar competitor,” according to PhRMA’s report. Guth said that this component of the IRA could have positive implications for biologics developers. That’s because biologics, which will be subject to price negotiation after 13 years of market exclusivity, are excluded from pricing negotiation if they already face biosimilar competition or will in the next two years. This “may create an environment in which originators are more amenable to biosimilar entry than previously because it provides some level of protection from near-term negotiation,” Guth said. But, the IRA can also disincentivize biosimilar development, he added—if negotiation brings down pricing prior to biosimilar entry. This would limit the potential incentive to develop biosimilars, Guth said. Margery Fischbein, managing director of healthcare at Cassel Salpeter & Co., agreed that this could happen. “An unintended consequence of the IRA is that generic and biosimilar manufacturers may be disincentivized to enter the market given their pricing advantages relative to Medicare negotiated brand name drugs may no longer be attractive,” Fischbein told BioSpace. Guth said what the industry should be watching is the specific products CMS will identify for negotiation and the beginning of the price negotiation meetings between CMS and the manufacturers of those products. CMS will announce the first ten drugs selected for negotiation under Medicare Part B by September 1. “The uncertainty for biosimilars generated by the IRA—both in terms of rebates and price negotiation—has not been fully anticipated by the lawmakers,” Guth said. Ana Mulero is a freelance writer based in Puerto Rico. She can be reached at anacmulero@outlook.com and @anitamulero on Twitter.