Competition for the epidermal growth factor receptor (EGFR) exon 20 insertion mutation non-small cell lung cancer (NSCLC) treatment market is set to heat up with the launch of a second drug in Korea.

Takeda Pharmaceutical Korea held a press conference on Wednesday to launch Exkivity (ingredient: mobocertinib), a treatment for EGFR exon 20 insertion mutation NSCLC that received approval from the Ministry of Food and Drug Safety in July last year.

EGFR exon 20 insertion mutations are rare, accounting for about 10 percent of EGFR-mutated NSCLC cases and about 2 percent of all NSCLC cases.

Compared to exon 19 deletion and exon 21 (L858R) substitution mutations, which account for most of the EGFR mutations, the survival period is twice as short, and existing EGFR mutation-targeted therapies have shown to be ineffective against exon 20 insertion mutations.

Professor Ahn Myung-joo (second from right) and Professor Kim Tae-min (to Ahn's left) answer questions from reporters during a Q&A session during a press conference at the Plaza Hotel Seoul on Wednesday.
Professor Ahn Myung-joo (second from right) and Professor Kim Tae-min (to Ahn's left) answer questions from reporters during a Q&A session during a press conference at the Plaza Hotel Seoul on Wednesday.

Exkivity is a targeted treatment for EGFR exon 20 insertion mutation NSCLC that can be used as a second-line treatment for patients who have previously been treated with platinum-based chemotherapy. Until now, the only treatment available for such patients was Janssen's Rybrevant (ingredient: amivantamab).

As Takeda launched Exkivity in Korea in earnest,  competition with Janssen Rybrevant is inevitable.

Although no trials directly compared the two drugs head-to-head, separate trials have shown that the overall survival (OS) and progression-free survival (PFS) indicators for Rybrevant are higher than Exkivity.

Also, the CHRYSALIS study, which is based on Rybrevant approval, showed that the overall response rate (ORR) of Rybrevant monotherapy was tallied at 40 percent, which was higher than Exkivity's ORR of 28 percent.

In addition, Rybrevant's median duration of response (DoR) was 11.1 months and the median PFS was 8.3 months. While Exkivity's DoR was longer at 17.5 months, its PFS was 7.3 months, a month shorter than Rybrevant.

Despite such shortcomings, Professor Kim Tae-min of the Department of Hemato-oncology at Seoul National University Hospital stressed that the longer DoR for Exkivity was a plus.

"One of the most important indicators when confirming the effectiveness of a targeted anticancer drug is the DoR," Professor Kim said. "A longer DoR means that the drug's effect last longer, which can ultimately lead to an extension of the patient's survival time."

Professor Ahn Myung-joo of the Department of Hemato-oncology at Samsung Medical Center noted that as Exkivity is the only oral formulation that can be taken once a day regardless of meals, it will help greatly improve convenience.

"Exkivity can help patients improve their quality of life in that they can easily take it by themselves," Ahn said.

Kim also predicted that adverse reaction management would be the key to what treatment will preoccupy the market.

Since Rybrevant is an injectable drug, infusion-related adverse reactions (IRRs) occur. In addition, since it is a monoclonal antibody there are unique side effects, such as skin rash.

As Exkivity is an oral medication, there are no such side effects.

However, Kim noted that adverse reactions occurred in all patients who received Exkivity. Grade 3 or higher adverse reactions occurred in 66 percent of patients.

"A notable adverse reaction is a diarrhea," Professor Kim said. "Diarrhea occurred in 93 percent of patients receiving Exkivity."

Notably, 16 percent of patients experienced grade 3 or higher diarrhea, experiencing diarrhea seven or more times a day, Kim added.

As a result, both experts agreed that it is necessary to find a suitable patient group for each drug through additional research.

"Each patient's response to the drug is different," Professor Kim said. "Some patients respond only to Exkivity or Rybrevant, and others to both.

It is necessary to conduct an analysis with additional data, Kim added.

Kim also stressed that as the two drugs show differences in formulation and adverse reactions, so it is necessary to determine the appropriate drug through close communication with the patient.

Professor Ahn agreed.

"One thing to note is that only about 100 patients have participated in the current clinical trial, so it is dangerous to compare and judge the two drugs based on this data," Professor Ahn said. "While it is clear that the effect of the two drugs is better than existing drugs, more data will need to be accumulated to judge the two drugs."

 

 

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