Global pharmaceutical companies speed up the development of subcutaneous (SC) formulations of their proprietary intravenous (IV) medications.

To overcome the disadvantage of IV formulation medications that have long administration duration, more anti-cancer drugs are shifting to SC formulations. Following the trend, Korean companies with SC formulation technology are gaining attention.

Then, what can we predict about the success in real-world clinical practices? While the shift to SC formulation of anti-cancer drugs is trending, pharmaceutical‧biotech industries focus on real-world clinical practices.

According to pharmaceutical and biotech companies on August 24th, global pharmaceutical companies with proprietary IV formulations of anti-cancer drugs are proactively conducting clinical trials to transition to SC formulation products.

SC formulation products are injected into the subcutaneous layer of the skin. Injection sites are typically arms, thighs, and abdominal region.

Until now, anti-cancer drugs were available primarily as IV formulations, which inject medications into veins. IV formulation has the advantages of fast absorption and accurate administration but has the disadvantage of taking a long time. For IV injection of anti-cancer drugs, patients were burdened by having to visit hospitals and withstand four to five hours of needle insertion.

In contrast, developing anti-cancer drugs as SC formulations has the advantage of substantially improving patient convenience of administration. The administration duration was reduced from a couple of hours to a maximum of ten minutes. Therefore, patients do not need to stay in the hospital for a long time for anti-cancer drugs.

As a result, global pharmaceutical companies with immune checkpoint inhibitors are proactively conducting clinical trials and applying for approvals to transition to SC formulations.

Following Roche's 'Tecentriq (atezolizumab)' SC obtaining marketing authorization from the European Medicines Agency (EMA) in January, BMS and Ono Pharmaceutical's R&D of 'Opdivo (nivolumab)' and 'Rybrevant (amivantamab)' is nearing the end.

These immune checkpoint inhibitors share the same goal to defend against their sales decrease due to patent expiration.

Furthermore, the development of SC formulation products has gained more attention since SC formulations have a greater advantage in patient access in the global market, especially in the U.S. market.

Recently, J&J confirmed the non-inferiority of SC formulations compared to IV formulations through the Phase 3 PALOMA-3 study, presented at the American Society of Clinical Oncology (ASCO) meeting. Based on the results, J&J has recently applied for additional U.S. FDA approval on Rybrevant SC formulation.

Professor Byoung Chul Cho (Director of the Lung Cancer Center at Yonsei Cancer Hospital) said, "The United States provides incentives to using injections, and the amount of incentives is the same between IV injectable or SC injectable," and explained, "There is no need to maintain IV formulation injectables, which commonly induce injection-associated adverse reactions."

Professor Sun Min Lim (Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Hospital) also said, "SC injectables only take 1-2 minutes for Rybrevant administration. The common adverse reactions of IV injectables are fever and lowered blood pressure," and added, "In my opinion, SC injectables can reduce such adverse reactions."

In the global market trend, clinical practices in South Korea are accelerating the introduction of SC formulation products, which overcome the previous disadvantages of IV formulation.

For example, Roche's Phesgo has been recently introduced with reimbursement.

Phesgo is an anti-cancer drug developed by changing the IV formulations of Herceptin (trastuzumab) and Perjeta (pertuzumab) to SC formulations. It received approval in September 2021 as the first investigational biopharmaceutical.

Phesgo was developed by combining two IV formulation products into SC formulation. It is known to decrease the administration duration for patients with breast cancer substantially. It has been designated as an innovative new drug (IND) and is reimbursable, leading to its recent use in clinical practices. If patients with metastatic HER2-positive breast cancer who have been receiving the maintenance therapy, IV formulations of Herceptin plus Perjeta every three weeks, were to change to Phesgo SC, administration and monitoring duration is expected to decrease from over four hours to 20 minutes.

The remaining step is whether the SC formulation can be used in clinical practices in South Korea.

While there are clear advantages in patient administration, there are opinions that, unlike in the global market, such as the U.S., it is challenging to quickly replace the existing market in South Korea due to geographic accessibility. Additionally, many believe it will be challenging for healthcare professionals to readily switch to the SC formulation, which they have yet to experience.

However, some argue that the fact that most cancer drug administrations are carried out primarily in large hospitals and are performed in the same way in injection rooms is more positive. The large number of patients who can receive treatment may facilitate the rapid establishment of the SC formulation.

Professor Park Yeon Hee (Division of Hematolology-Oncology at Samsung Medical Center) said, "Korean patients tend to wait in the hospital, and there are long waits in large hospitals. Therefore, patients may prefer switching to SC formulations," and stated, "In clinical practices, patients may prefer IV injection despite the wait as SC prescriptions, other than clinical studies, have only been made recently."