"Leclaza’s excellence is evident not only in clinical trials but also in clinical practice. Reimbursement coverage is essential from both the patient's and the medical professional's perspective."
[National lung cancer drug 'Leclaza'] ① "Yuhan Corporation's EAP program has been very helpful, a continuous usage environment without financial burden is needed."

Expectations for the results of the global Phase III clinical trial (MARIPOSA) with combination therapy... Ultimately, the increase in treatment options benefits patients.
Article written for the approval of the first korean lung cancer drug 'Leclaza' as a first-line treatment

[관련기사="렉라자 1차치료 임상 물론 진료현장에서도 우수성 느껴…환자·의료진 입장 급여 적용 필수"]
 
The domestic lung cancer drug, Leclaza (lazertinib), produced by Yuhan Corporation, received approval from the Ministry of Food and Drug Safety at the end of June this year to expand its indications as a 'first-line treatment' for locally advanced or metastatic non-small cell lung cancer patients with EGFR exon 19 deletion or exon 21 (L858R) substitution mutations. Just three months later, it has also gained recognition for appropriateness of coverage from the Health Insurance

Review and Assessment Service's Drug Reimbursement Evaluation Committee, paving the way for expanded insurance coverage to take effect in early next year. This development is attributed to the results obtained from the LASER301 clinical trial, which confirmed its efficacy and safety for first-line treatment.

The LASER301 is a clinical trial, randomized, double-blind, multinational Phase III study, conducted in 13 countries across 96 institutions. It aimed to evaluate the efficacy and safety of Leclaza compared to Gefitinib in the first-line treatment of 393 patients with previously untreated locally advanced or metastatic non-small cell lung cancer who had active EGFR mutations. Of these patients, 258 were Asian (including 172 Koreans), and 135 were non-Asian.

The clinical results indicated that when Leclaza was used as a first-line treatment, it achieved a progression-free survival (PFS) of 20.6 months. This was a statistically significant improvement compared to the control group, which received first-generation treatment with Gefitinib and achieved a PFS of 9.7 months.

The analysis of subgroups based on EGFR mutation types also showed superior effects of Leclaza. In an interview with Dr. Lee Yoon-kyu, an expert in lung cancer from the Samsung Medical Center at Sungkyunkwan University School of Medicine, the discussion focused on the first-line treatment effectiveness and safety of the domestic anticancer drug Leclaza, the significance of adding it as a first-line treatment option, and the outlook for the future treatment paradigm for EGFR-mutated non-small cell lung cancer, especially in light of the MARIPOSA clinical trial.

Leclaza had previously received approval from the Ministry of Food and Drug Safety as a second-line treatment for EGFR T790M mutation-positive patients on January 18, 2021, securing its position as the 31st domestic new drug.
 
Yuhan Corporation conducted a multinational Phase III clinical trial called LASER301 for the first-line treatment of non-small cell lung cancer with positive EGFR activating mutations, beginning in October of last year. The trial statistically confirmed a significant improvement in progression-free survival (PFS). Based on these results, they submitted an application to the Ministry of Food and Drug Safety in March this year for expanding the drug's indications to include the first-line treatment of non-small cell lung cancer with positive EGFR activating mutations. This application received approval in late June.

Subsequently, in just two months following the expanded approval, the Health Insurance Review and Assessment Service (HIRA) established reimbursement criteria for Leclaza’s use in the first-line treatment of patients with locally advanced or metastatic non-small cell lung cancer who have EGFR exon 19 deletion or exon 21 (L858R) substitution mutations, during a meeting of the Cancer Medicines Review Committee (Cancer MedSAC) in late August. Additionally, HIRA acknowledged the appropriateness of reimbursement during a meeting held on the 12th of the last month.

The analysis results of the LASER301 clinical trial's Asian subgroup were presented as a poster at the World Conference on Lung Cancer (WCLC 2023), which took place last month, attracting significant attention.
 
Why was the pace of expansion of indications and reimbursement for first-line treatments so rapid? Solid clinical evidence.

The professor mentioned, "Leclaza achieved a progression-free survival (PFS) of 20.6 months, and the more noteworthy aspect is that the PFS of 20.6 months for the entire global patient population remained consistent across different racial backgrounds." He further stated, "Even in the subgroup analysis specific to Asians, PFS was 20.6 months. The results for the Korean subgroup were also consistent, showing 20.8 months." He went on to emphasize, "For some medications, the effectiveness of treatment can vary significantly depending on the patient's racial background. However, Leclaza's consistent performance across racial groups indicates that it can be applied as a treatment option regardless of race."

Not only across different racial backgrounds but also within various EGFR mutation subtypes, Leclaza's exceptional effectiveness was confirmed. In fact, according to the clinical results, patients with Exon 19 deletion mutation (Ex19del) achieved a Leclaza PFS of 20.7 months. Even in the patient group known for relatively poor treatment outcomes compared to those with Exon 19 deletion mutations, such as those with Exon 21 L858R substitution mutation (L858R), Leclaza demonstrated a superior anti-tumor effect, with a PFS of 17.8 months.

The professor remarked, "Because treatment outcomes can vary depending on the mutation subtype, researchers have shown significant interest in developing drugs that can overcome this challenge and have made various efforts to find solutions." He further noted, "In particular, traditional targeted therapies have shown considerably reduced treatment effectiveness for patients with the Exon 21 L858R substitution mutation compared to those with Exon 19 deletion mutations. In this context, the clinical results from the LASER301 trial, which forms the basis for Leclaza's first-line treatment, are noteworthy for demonstrating Leclaza's excellent anti-tumor effects even in patients with the Exon 21 L858R substitution mutation."
 
The professor also emphasized the superior effectiveness of treatment for brain metastases. The professor stated, "Brain metastasis is a common clinical outcome in all solid tumors. Cancer cells spread throughout the body, ultimately progressing to brain metastasis." He further explained, "In the case of non-small cell lung cancer patients with EGFR mutations, brain metastases were found in approximately 20-30% of patients at the time of diagnosis, and during the course of treatment, over half of these patients were observed to have brain metastases until the time of death."

In other words, the management and treatment of brain metastases are of paramount importance in non-small cell lung cancer patients. The professor stated, "When brain metastases occur, they not only lead to cognitive impairment but also result in motor function disabilities, such as loss of sensation in the limbs." He added, "Therefore, the markedly superior efficacy of Leclaza in controlling brain metastases during first-line treatment is highly meaningful for improving the quality of life for patients."
 
Leclaza, with its very low molecular weight, effectively penetrates the blood-brain barrier (BBB) compared to traditional treatments, resulting in significantly enhanced brain activity. Consequently, it can address brain metastases, a capability that has been substantially expanded. When the data of domestic patients were analyzed in particular, its effectiveness was even more pronounced, attracting the attention of the medical community.

This efficacy has not been confined to clinical trials alone. As a professor who has prescribed Leclaza as a first-line treatment through Phase III clinical trials and large-scale Early Access Programs (EAP), he noted, "Patients are providing positive feedback, stating that they experience excellent initial responses, and the response is fast." He further mentioned, "In reality, patients report dramatic symptom improvements occurring as soon as one to two weeks, or in some cases, as quickly as one month after taking the medication, resulting in high satisfaction among those who have been prescribed Leclaza."

He continued by saying, "The expansion of first-line treatment options through the development of Leclaza is a positive development from a medical standpoint as well. Since one drug doesn't yield the same results for every patient when treating cancer, having high-efficacy treatment choices can potentially contribute to increasing the disease's cure rate."

No matter how effective a drug is, if it's too expensive, it might not be accessible. The introduction of an EAP (Early Access Program) is seen as a positive step.

No matter how effective a treatment is, if it is excessively expensive, it's just an unattainable luxury. However, Leclaza has received high praise for being accessible without a heavy financial burden.

The professor mentioned, "In recent times, patients and their caregivers are quickly gaining information about new medications through various specialized sources. However, if the medication is not covered by insurance, its use might be limited due to economic constraints." He went on to say, "Yuhan Corporation, based on the LASER301 clinical results, expanded the indications rapidly and is currently implementing a large-scale Early Access Program (EAP) to ensure that patients can use it without significant financial burden."

He continued, "In this aspect, a domestic company has taken proactive measures where multinational companies have not, setting a positive precedent not only for patients and their caregivers but also for the public. Over ten patients have already registered for EAP benefits at Kangbuk Samsung Hospital," he said. "It goes beyond merely developing an effective drug, offering hope and opportunities to patients by supporting them from development to actual use."

He also anticipated that, based on the clinical trials that have proven high efficacy, the rapid expansion of insurance coverage procedures would allow patients to continue using the medication with minimal financial burden. Furthermore, it's worth noting that the interim results of the MARIPOSA Phase III clinical trial are expected to be presented at the upcoming European Society for Medical Oncology Annual Congress (ESMO 2023).

This involves a global Phase III clinical trial comparing Leclaza-Rybrevant combination therapy to Leclaza monotherapy and Tagrisso monotherapy in non-small cell lung cancer patients with exon 19 deletion or L858R substitution mutations. Given the previous confirmation of a 20.6-month progression-free survival (PFS) with Leclaza monotherapy, there is considerable anticipation about how much the combination therapy with two targeted treatments can extend the survival period.

The professor mentioned, "The challenge with targeted therapies is that while they are effective, drug resistance can develop over extended periods of use. As a result, efforts are underway to develop combination therapies to prevent the development of resistance genes from the outset and maintain effectiveness over the long term." He further stated, "We need to wait for specific data, but many lung cancer researchers are looking forward to the results of the MARIPOSA clinical study. If it demonstrates synergy and effectively prevents the development of resistance genes, it is expected to significantly improve treatment outcomes."

by Min-ji Seo