Multinational pharmaceutical companies are actively pursuing to secure reimbursement for their anti-cancer drugs as first-line treatment options.

Based on accumulated clinical research, companies are competitively applying for reimbursement from the government, putting in all efforts to accomplish this by the second half of this year.

Recently, several argued that the current reimbursement review paradigm, which has focused on 'life extension,' should undergo a significant transformation to center around the 'improvement of quality of life.' In other words, they argue that reimbursement should be discussed primarily for first-line treatment options, rather than late-stage treatments for specific cancers, with a focus on directly improving quality of life.

According to the pharmaceutical industry, on July 14, multinational pharmaceutical companies have recently applied to the Health Insurance Review & Assessment Service (HIRA) for reimbursement of their anti-cancer drugs as first-line treatment options.

For instance, 'Astellas Pharma Korea' is one of them.

Astellas recently re-applied for reimbursement for the Padcev (enfortumab vedotin)-Keytruda (pembrolizumab, MSD) combination therapy as a first-line treatment for urothelial carcinoma. In addition, they concurrently applied for Padcev monotherapy for second-line or later treatment.

Notably, Astellas re-applied for both first-line and second-line or later treatments at once, bringing both therapies to the Cancer Disease Review Committee (CDRC) discussion table. While the monotherapy, used in second-line or latertreatment, had passed the CDRC and was undergoing cost-effectiveness evaluation, the combination therapy obtained domestic approval and rapidly gained presence in clinical settings. Therefore, the analysis suggests that Astellas resubmitted both together.

In other words, both the combination therapy and monotherapy are now on the CDRC table for discussion.

Dr. In-Keun Park of Asan Medical Center, Seoul (Department of Oncology), said, "Using Padcev earlier in the treatment has an advantage in terms of overall survival (OS) compared to using it later." He added, "Realistically, due to cost issues, the dosage is often adjusted (contrary to clinical standards). In some cases, patients are even reducing their body weight to lower the drug dosage due to drug costs."

Dr. Park added, "In clinical practice, the proportion of patients who transition from first-line to second-line treatment, and from second-line to third-line treatment, decreases sharply," and emphasized, "Considering that first-line combination therapies are already introduced and used in Korea, discussions for reimbursement of first-line combination therapies can no longer be delayed."

Furthermore, the competition for reimbursement of first-line treatments to secure market dominance in the gastric cancer treatment market in the second half of this year is accelerating.

Keytruda passed the CDRC in the first half of this year and is currently undergoing cost-effectiveness evaluation at a subcommittee of the Drug Reimbursement Evaluation Committee (DREC). As the only immunotherapy that can be used not only in HER2-negative but also HER2-positive patients, Keytruda, as a first-line option in Stage 4 gastric cancer treatment, is expected to grow significantly depending on whether reimbursement is applied.

Additionally, BeOne Medicines Korea (formerly BeiGene Korea) has also applied to HIRA for reimbursement for five new indications, including gastric cancer, for its immunotherapy Tevimbra (tislelizumab). This means that BeOne Medicines Korea had immediately applied for HIRA after obtaining domestic approval by the MFDS in June.

Additionally, Astellas has also re-applied for reimbursement for 'Vyloy (zolbetuximab),' a Claudin 18.2 gastric cancer targeted therapy. The company has recently been promoting this drug alongside Padcev. This re-application comes approximately four months after Astellas failed to achieve reimbursement listing from the CDRC in February.

An Astellas official explained, "Korean medical professionals and patients sincerely hope for rapid reimbursement of Vyloy in the treatment of HER2-negative and Claudin 18.2-positive metastatic gastric cancer, where there are no other treatment options." He added, "We have faithfully reflected HIRA's supplementary requests and completed the re-application for reimbursement. We will do our best to ensure that the best treatment option is quickly introduced to patients."

As multinational pharmaceutical companies continue to aim for reimbursement of anti-cancer drugs as first-line treatment options, the government authorities will likely face an increased load of responsibility for evaluation. This is because reimbursement of initial treatments naturally leads to increased financial burden on the national health insurance.

However, reimbursement cannot be denied for treatments with proven efficacy in clinical research due to the financial burden.

Therefore, opinions are emerging that the government's reimbursement discussion paradigm must undergo a significant transformation. They imply that a shift in the discussion focus from 'life extension' to 'improvement of quality of life.'

In fact, until now, both the government and pharmaceutical companies have primarily discussed reimbursement by first applying it to second-line and subsequent treatments, then expanding coverage to first-line treatment. However, with recent cases demonstrating both clinical efficacy and OS benefits from first-line treatment, the prevailing opinion is that it is no longer easy to maintain this approach.

For instance, Rybrevant (amivantamab, Johnson & Johnson) is an example. Recently, results from the MARIPOSA Phase 3 trial were announced, showing that the combination therapy with Rybrevant and Lazertinib (Yuhan Corp) as a first-line treatment for non-small cell lung cancer could extend OS by over 50 months.

Based on these results, Johnson & Johnson applied for reimbursement for the Rybrevant-Lazertinib combination therapy as a first-line option to HIRA in the first half of this year.

Therefore, the pharmaceutical industry is suggesting that the medical community and the government must find a common ground through discussions on a paradigm shift in reimbursement, starting with anti-cancer drugs.

It suggests revising the reimbursement system to encourage more proactive treatment from the initial stages, shifting the focus from life extension to quality of life.

An anonymous pharmaceutical industry official said, "The current reimbursement system for anticancer treatment is in a transitional period. With an increasing number of options proving treatment efficacy from the initial stages, the time to discuss reimbursement primarily for fourth or fifth-line treatments seems to have passed," and added, "It seems we are transitioning to an era where priority is given to actively treating patients early on to improve their quality of life ultimately, rather than focusing on treatments that merely extend life slightly."

He added, "Currently, we are at a stage of confusion regarding the reimbursement priority between initial treatment and subsequent retrospective treatments. It's a question of whether to focus on life extension, or to recognize efficacy based on progression-free survival (PFS) in initial treatment even if OS is not extended." He stressed, "While the financial costs will undoubtedly be greater, it's now time for a specific policy direction."