Indication for rare cancer drug Retevmo is expanded

But makes slow progress in its reimbursement in Korea

RET-targeted anticancer drug Retevmo’s indication is expanded to allow use in patients under 12 years old

Shows improvement in major endpoints in clinical studies...will the data support domestic reimbursement

The indication for Retevmo, which targets a rare disease mutation in lung cancer, has been expanded to include children with solid tumors across the spectrum.

 

Retevmo is approved in South Korea for lung cancer but not reimbursed in Korea.

 

It will be interesting to see if the additional confirmation of clinical efficacy will have an impact on its insurance reimbursement progress in Korea.

 

According to industry sources on the 1st, the U.S.

 

Food and Drug Administration (FDA) expanded the approval for Retevmo, a treatment targeting the RET (REarranged during Transfection) gene mutation, for pediatric patients with thyroid cancer and solid tumors for which there are no treatment alternatives.

 

As a result, Retevmo became the first targeted therapy for pediatric patients with RET-mutant cancers under the age of 12.

 

This is an accelerated approval and is subject to further confirmatory clinical studies to determine full approval.

 

In addition to the existing RET-mutant lung cancer indication, Retevmo is now available for pediatric patients with RET-mutant metastatic medullary thyroid cancer, RET-mutant radioactive iodine-refractory advanced or metastatic thyroid cancer, and RET-mutant locally advanced or metastatic solid tumors for which there are no alternative treatment options during or after systemic therapy.

 

The expanded approvals were based on the Phase I/II LIBRETTO-121 trial, which assessed Retevmo in 25 patients aged 2-20 with advanced or metastatic RET-activated solid tumors who had little response.

 

The primary endpoints were overall response rate (ORR) and duration of response (DOR).

 

Results showed a confirmed ORR of 48%, as determined by a blinded independent review committee.

 

The median duration of response (DOR) was not reached and 92% of responders had responses lasting 12 months.

 

In terms of safety, the most common adverse events were musculoskeletal pain, diarrhea, headache, nausea, vomiting, coronavirus infection, abdominal pain, fatigue, pyrexia, and bleeding.

 

The most common grade 3 or 4 adverse reactions were calcium decrease, hemoglobin decrease, and neutropenia.

 

Sustained responses were observed in pediatric and young adult patients with RET-mutated pheochromocytoma.

 

The most common adverse reactions reported were musculoskeletal pain, diarrhea, headache, nausea, vomiting, COVID-19, abdominal pain, fatigue, pyrexia, and hemorrhage.

 

The most common grade 3 or 4 laboratory abnormalities were decreased calcium, hemoglobin, and neutrophils.

 

Retevmo makes slow domestic reimbursement progress Currently, Retevmo is making slow reimbursement progress in Korea.

 

In May last year, Retevmo was recognized for its reimbursement adequacy by the Health Insurance Review and Assessment Service’s Drug Reimbursement Evaluation Committee, but since failed to negotiate drug prices with the National Health Insurance Service and remains unreimbursed.

 

In particular, with Roche's RET mutant-targeted therapy Gavreto withdrawn from the market, Retevmo is the only drug in the market but is not easily administrable due to its non-reimbursed status.

 

In Korea, Retevmo is approved for the treatment of▲ adult patients with metastatic RET fusion-positive non-small cell lung cancer (NSCLC); ▲adults and pediatric patients 12 years of age or older with advanced or metastatic RET-mutated medullary thyroid cancer who require systemic therapy; and ▲ adult patients who are refractory to radioactive iodine therapy and who have prior sorafenib and/or lenvatinib treatment, with advanced or metastatic RET-fusion benign thyroid cancer who require systemic therapy.

 

NSCLC patient with RET mutation is classified as a rare cancer.

 

RET mutations occur in 2 to 6 % of all NSCLC cases and are more often found in adenocarcinomas and younger patients under 60 years of age and non-smokers.

 

In NSCLC, RET fusions occur more than RET mutations.

 

In thyroid cancer, RET fusions are reported in up to 40% of the cases.

 

While there are several treatments available for EGFR-mutant lung cancer, including Tagrisso, Leclaza, and Rybrevant, Retevmo remains the only option for RET-mutant lung cancer.

 

Therefore, it will be interesting to see if Retevmo, which has expanded its indications to pediatric thyroid cancer and solid tumors, can play an active role in Korea.