Samsung Bioepis has developed its own subcutaneous (SC) injection formulation technology, expanding the global biosimilar competition into "formulation switching." Celltrion has already internalized PH20-based technology and last year began developing biosimilars of Herceptin SC and Darzalex SC. Some observers say biosimilar developers may be able to launch SC products immediately when original products' substance patents expire. As a result, SC formulation competition between the two major biosimilar makers and big pharma is expected to intensify.
According to the biotech industry on the 13th, Samsung Bioepis is reviewing plans to apply SC formulations. The company is currently developing biosimilars of Keytruda and Enhertu, and it is widely expected that Samsung Bioepis will apply the technology to these two drugs first. A biotech industry official explained, "Since waiting for the original SC product's patent to expire could delay market entry, the key will be when to begin development."
Merck's (MSD) Keytruda is the world's top-selling cancer drug, generating $31.7 billion in sales last year alone. MSD plans to convert 40% of the entire Keytruda market to the SC formulation "Keytruda Qlex" by the end of next year. By simple calculation, this would create a $12.7 billion market in the SC formulation alone. Enhertu, an antibody-drug conjugate (ADC) drug that generated $5 billion in sales last year, has also begun SC formulation development, and the SC drug market is expected to grow further. Market research firm Mordor Intelligence forecast that the global SC biopharmaceutical market will grow from $286.3 billion this year to $498.9 billion by 2031.
Samsung Bioepis has pursued internalizing PH20-based SC formulation technology because global big pharma companies are extending their market monopolies through SC formulations. In fact, Johnson & Johnson, after obtaining FDA approval for Darzalex Faspro—the SC formulation of Darzalex—in 2020, converted more than 80% of existing Darzalex patients (85% in the U.S., 80% in Europe) to Darzalex Faspro within about two years. Ahead of the Darzalex (IV) patent expiration in 2030, this leaves less than 20% of the market for biosimilar makers. Compared with IV formulations, SC formulations reduce administration time from several hours to several minutes and shorten hospital stays, making them highly preferred by both patients and medical staff.
Amid this market trend, Celltrion has already begun securing the world's first SC formulation biosimilar using hyaluronidase. It has been conducting clinical trials for approval of Herzuma SC (CT-P6 SC) since February last year, and began clinical trials of the SC formulation (CT-P44) of its Darzalex biosimilar in August last year. Celltrion is also considering expanding its formulation-switching CMO business for external clients as well as its own new drugs. Samsung Bioepis, on the other hand, was confirmed not to be considering providing its formulation-switching technology externally.
Notably, both major domestic biosimilar companies have secured their own SC platforms. Global biosimilar companies Switzerland's Sandoz and India's Intas have signed contracts with Korean firm Alteogen to license SC formulation-switching technology. However, Alteogen has signed exclusive contracts with MSD for the Keytruda ingredient and with Daiichi Sankyo for the Enhertu ingredient. Sandoz and Intas find it difficult to apply Alteogen's technology to Keytruda and Enhertu biosimilars. Halozyme, which participated in developing blockbuster SC formulations such as Herceptin, Darzalex, and Rybrevant, also provides its technology exclusively.
A biotech industry official said, "As platform companies sign exclusive contracts with big pharma for each ingredient, biosimilar makers without their own technology are now forced to wait until the SC formulation patents expire," adding, "While proprietary technology cannot completely rule out the possibility of patent disputes, it carries relatively lower risk and has the advantage of being applicable to various products once patent issues are resolved." The point is that building an SC platform based on a proprietary sequence allows it to be used as a general-purpose platform. Furthermore, there is speculation that companies may break away from the strategy of chasing original drugs' patent expiration and instead enter SC formulation competition immediately when substance patents expire.
Synergy in production with affiliates is also expected. Samsung Biologics, an affiliate of Samsung Bioepis, plans to expand production lines for pre-filled syringes (PFS) and auto-injectors used in SC formulations by 2027. These facilities could later be used derivatively to produce drug products (DP) for SC formulation biosimilars. Celltrion Pharm, an affiliate of Celltrion, has also disclosed plans to invest 2 trillion won in North Chungcheong Province to expand its PFS production capacity from the current 20 million syringes per year to 70 million syringes.
Meanwhile, Alteogen issued a statement that day, emphasizing, "Keytruda Qlex can be protected by exclusive rights under patents until 2043, when the ALT-B4 U.S. substance patent expires," and "We have built a diverse patent portfolio including not only substance patents but also fixed-dose and formulation-related patents." It added, "We judge that a product applying a completely different substance (API) from ALT-B4 would find it difficult to be approved as a biosimilar of Keytruda Qlex."
Since biosimilars are approved on the premise of the same substance, formulation, and dosage as the original, the point is that using one's own hyaluronidase would likely classify the product as a new drug rather than a biosimilar. Typically, a formulation-change new drug takes about five years to develop, and under current FDA regulations, it is not granted substitution with the original even after commercialization. Samsung Bioepis is reported to have reviewed various approval procedures, including biosimilars and formulation-change new drugs, while developing this technology.
