Immunotherapies seek revenue growth by expanding indications

Immunotherapies, mainly used for stage 4 treatments, are expanding their indications to pre- and postoperative treatments of earlier-stage lung cancer. Accordingly, the domestic immunotherapy market will grow even further.

From left are Opdivo, Tecentriq, and Keytruda.

The combined sales of two such drugs – Opdivo (nivolumab) of Ono Pharma and BMS and Tecentriq (atezolizumab) of Roche – exceeded 200 billion won ($151 million). If MSD’s Keytruda (pembrolizumab) joins them, the market will reach over 400 billion won.

Last October, Opdivo won approval from the Ministry of Food and Drug Safety to add to its indication pre-operative neoadjuvant therapy to treat “resectable non-small cell lung cancer (with a tumor sized 4 centimeters and larger or benign limp node) in combined administration with platinum-based chemotherapy.” Opdivo has 22 indications for 10 cancers in Korea.

The approval was based on the Checkmate-816 study.

According to the study, Opdivo’s median value of event-free survival (EFS) was 31.6 months compared with the control group’s 20.8 months.

The study showed that its pathological complete remission (pCR) was 24 percent compared with the control group’s 2.2 percent, confirming clinically significant improvement.

Stage 4 NSCLC patients can use Opdivo depending on their PD-L1 expression rate or genetic mutation. However, regardless of those conditions, it can be used as a pre-operative adjuvant therapy.

Tecentriq also added its indications last November to postoperative adjuvant for stage 2-3A NSCLC patients with a PD-L1 expression rate of 50 percent of tumor cells and higher after undergoing resection or platinum-based chemotherapy. Accordingly, Tecentriq has eight indications for five cancers.

The approval was based on interim analysis results of the IMpower 010 study.

It showed Tecentriq reduced disease-free survival (DFS) by 57 percent compared to best supportive care in stage 2-3A NSCLC patients with a PD-L1 expression rate of 50 percent and higher after undergoing complete resection or platinum-based chemotherapy.

Such expanded indications have pushed the sales of Opdivo and Tecentriq.

According to IQVIA, Opdivo’s 2021 sales totaled 85 billion won but increased 29.3 percent to 109.9 billion last year. Tecentriq also saw revenue growth of 21.7 percent, from 67.2 billion won to 81.8 billion won. The two marked combined sales of 191.7 billion won in 2022.

Both are preparing for reimbursement for pre- and postoperative lung cancer treatment to expand their sales further.

Keytruda seeks indications of pre- and postoperative early-stage lung cancer

Keytruda is aiming to expand its indications even broader than the two drugs. It already won approval for postoperative therapy from the U.S. Food and Drug Administration in January.

FDA gave the nod based on the drug’s phase 3 clinical trial of the KEYNOTE study. According to the study, Keytruda reduced DFS by 27 percent regardless of PD-L1 expression. The primary endpoint of the median DFS (mDFS) value was 58.7 months for the Keytruda group and 34.9 months for the placebo group.

Besides, MSD released the KEYNOTE-671 study in March, comparing Keytruda adjuvant therapy’s effects in stage 2-3B NSCLC patients before and after operations with those of chemotherapy.

In the study, the Keytruda group was administered a combined therapy of Keytruda and chemotherapy before operations and with Keytruda alone after operations, while the placebo group received the combined therapy of placebo and chemotherapy before operations and the placebo alone after operations.

As a result, the Keytruda group showed statistically significant EFS improvement compared to the control group. It also confirmed significant improvement in the secondary endpoint of pCR and major pathological response (mPR).

Even before obtaining an indication for postoperative adjuvant therapy in Korea, Keytruda’s sales surpassed 200 billion won in 2021 and reached 239.6 billion won last year, up 19.7 percent.

If it adds indication regardless of PD-L1 expression, Keytruda will likely target more patients than Tecentriq.