Keytruda Gains New NMPA Approval for First-Line Treatment of Metastatic Non-Squamous NSCLC in China

Med ValleyLatest News: The National Medical Products Administration (NMPA) has approved the new indication application for Keytruda (commonly known as K Drug; application number JXSS1800018). It is now approved for use in combination with pemetrexed and cisplatin as a first-line treatment for metastatic non-squamous non-small cell lung cancer (NSCLC) that is EGFR- and ALK-negative. This marks the first expansion of indications for Keytruda in China, following its initial NMPA approval on July 25, 2018, for the treatment of patients with locally advanced or metastatic melanoma who experienced disease progression after first-line therapy. Concurrently, Keytruda has become the first immunotherapy approved for first-line treatment in China. Globally, only Keytruda and Roche’s Tecentriq have been approved for first-line treatment of NSCLC, with the latter currently still undergoing registration review in China.

In fact, the U.S. FDA had already formally approved on August 20 and October 31, 2018, respectively, the indications for Keytruda in combination with standard chemotherapy (pemetrexed and cisplatin/carboplatin) as first-line treatment for non-squamous non-small cell lung cancer (NSCLC), and for Keytruda in combination with standard chemotherapy (carboplatin and paclitaxel or carboplatin and albumin-bound paclitaxel) as first-line treatment for squamous NSCLC. Meanwhile, the Center for Drug Evaluation (CDE) under China’s National Medical Products Administration (NMPA) accepted the applications for review of Keytruda in combination with standard chemotherapy as first-line treatment for non-squamous NSCLC and squamous NSCLC on September 12 and October 22, 2018, respectively.

According to reports from Pineapple Factor, the approval of Keytruda for first-line treatment of lung cancer primarily relied on a clinical trial coded as KEYNOTE-189. At the 2018 European Society for Medical Oncology (ESMO) Immuno-Oncology Congress, the published data from the KEYNOTE-189 trial demonstrated that pembrolizumab combined with chemotherapy was significantly superior, regardless of whether cisplatin or carboplatin was used.

In patients receiving pembrolizumab in combination with pemetrexed and platinum agents (including carboplatin and cisplatin), significantly superior OS, PFS, and ORR were observed compared to the placebo group. Among patients treated with carboplatin, pembrolizumab combined with pemetrexed and carboplatin (n=297) versus chemotherapy alone (n=148) resulted in mOS of not reached versus 11.3 months, HR 0.52 (0.39-0.71); and mPFS of 8.6 months versus 4.9 months, HR 0.55 (0.44-0.70).

In patients receiving cisplatin-based therapy, pembrolizumab plus pemetrexed and cisplatin (n=113) versus chemotherapy alone (n=58) resulted in median overall survival (mOS) of not reached versus 10.8 months (HR 0.41 [95% CI, 0.24–0.69]) and median progression-free survival (mPFS) of 9.2 months versus 4.8 months (HR 0.44 [95% CI, 0.30–0.65]).

Overall, the combination of Keytruda and chemotherapy achieved an overall response rate (the proportion of patients with significant tumor shrinkage) of 48%, significantly improving overall survival and progression-free survival, and reducing the risk of death by 51%.

To date, a total of four PD-1 monoclonal antibody drugs have been approved for marketing in the Chinese market (two imported and two domestically produced), targeting multiple indications. The specific details are as follows:

Keytruda (Pembrolizumab)

R&D Pharmaceutical Company: MSD

Indications:It was approved by the National Medical Products Administration (NMPA) in July 2018 and March 2019, respectively, for the treatment of patients with locally advanced or metastatic melanoma who have experienced disease progression after first-line therapy, and in combination with pemetrexed and cisplatin as first-line treatment for EGFR- and ALK-negative metastatic non-squamous non-small cell lung cancer (NSCLC).

Price:The retail price in mainland China is CNY 17,918 per 100 mg. For patients weighing 50 kg or less, 17 doses are required annually, resulting in an approximate annual cost of CNY 300,000.

Charitable Assistance Program:For patients with minimum living allowance, meetingMedicineSubject to meeting the medical criteria and corresponding financial eligibility, the China Primary Health Care Foundation can provide patient assistance with Keytruda for a maximum duration of 24 months. Specifically, patients enrolled in the Minimum Livelihood Guarantee program may receive Keytruda free of charge. For low-income patients (those confirmed to have incurred catastrophic medical expenditures), upon satisfying the medical and financial eligibility requirements and after self-paying for three treatment cycles, the China Primary Health Care Foundation will provide assistance for an additional three treatment cycles. Subsequently, for every three treatment cycles self-paid by the patient, the Foundation will continue to provide assistance for another three treatment cycles, with the cumulative assistance period not exceeding 24 months. (Keytruda was included in the Shenzhen Medical Insurance scheme in November 2018.)

Opdivo (Nivolumab)

R&D Pharmaceutical Companies:Bristol-Myers Squibb

Indications:Approved by the National Medical Products Administration on June 15, 2018, for second-line treatment of adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) who are epidermal growth factor receptor (EGFR) mutation-negative and anaplastic lymphoma kinase (ALK)-negative, and whose disease has progressed or who are intolerant after prior platinum-based chemotherapy.

Price:In mainland China, the pricing is CNY 9,260 for 100 mg/10 mL and CNY 4,591 for 40 mg/10 mL. Based on a dosing regimen of 3 mg/kg administered via intravenous injection every two weeks, which requires one 100 mg/10 mL vial and two 40 mg/10 mL vials per dose, an adult patient weighing 60 kg incurs a cost of CNY 18,442 per dose, amounting to CNY 36,884 per month (for twice-monthly administration). In Hong Kong, the cost for the same scenario would be CNY 58,868. For an adult patient weighing 50 kg, requiring one 100 mg vial and one 40 mg vial per dose, the cost per administration is CNY 13,851, resulting in a monthly expense of CNY 27,702.

Charitable Assistance Program:Eligible recipients are adult patients in mainland China with locally advanced or metastatic non-small cell lung cancer (NSCLC) who are negative for epidermal growth factor receptor (EGFR) gene mutations and anaplastic lymphoma kinase (ALK), and whose disease has progressed or who have become intolerant after prior platinum-based chemotherapy. Specifically, eligible patients are categorized as either subsistence allowance recipients or low-income patients. Low-income patients refer to those from low-income groups who meet the medical criteria as diagnosed by designated medical institutions. Upon approval by the Project Office of the China Cancer Foundation, they may apply cyclically for assistance medications for each cycle in accordance with project requirements and procedures, receiving medication assistance for up to four cycles. The assistance plan for each cycle is defined as follows: after completing six consecutive doses of Opdivo® (at a single dose of 3 mg/kg administered once every two weeks, within a three-month period), if a designated physician assesses that the patient continues to benefit from Opdivo® treatment without disease progression and without intolerable side effects, and upon approval by the Project Office, the patient may receive free medication assistance for up to seven subsequent treatments.

Tuoyi (Toripalimab)

R&D Pharmaceutical Companies:Junshi Biosciences

Indications:Granted conditional approval by the National Medical Products Administration on December 17, 2018, for the treatment of patients with unresectable or metastatic melanoma who have failed prior systemic therapy.

Price: Priced at 7,200 yuan/240 mg (vial), equivalent to 30 yuan/mg, with an annual treatment cost of 187,200 yuan.

Charitable Assistance Program:The Beijing Bethune Public Welfare Foundation has launched the “Yi Lu Xiang Ban – Bethune·Tuoyi Public Welfare Donation Project” across China, providing medication assistance to melanoma patients from financially disadvantaged families or those impoverished by illness who cannot afford continuous and effective treatment. According to the project protocol, eligible patients will receive medication assistance for four cycles after completing four cycles of Tuoyi treatment. Preliminary estimates indicate that if this program covers one year or a longer treatment period, the patient’s actual annual out-of-pocket medication cost would be approximately RMB 93,600.

Tyvyt (Sintilimab)

R&D Pharmaceutical Companies:Innovent Biologics

Indications:Approved for marketing by the National Medical Products Administration on December 27, 2018, for the treatment of relapsed or refractory classical Hodgkin lymphoma in patients who have undergone at least two lines of systemic chemotherapy.

Price: Priced at 7,838 yuan/100 mg (vial)

Charitable Assistance Program:There are two assistance programs: one is the "Care·You" Shuxiang Xinsheng Membership Program initiated by a third party, where purchasing three cycles of sintilimab will grant two additional cycles of the product. Preliminary estimates suggest that after assistance, the patient's monthly treatment cost is approximately RMB 13,900, with an annual treatment cost of around RMB 167,000; the second is ChinaPharmaceuticalsThe China Pharmaceutical Innovation Promotion Association will join hands with Innovent Biologics (Suzhou) Co., Ltd. to jointly carry out the “China Pharmaceutical Innovation Promotion Association Tyvyt® Patient Assistance Program.” Eligible patients in mainland China who are registered as subsistence allowance recipients or impoverished households under the national poverty alleviation database may receive the medication free of charge through charitable assistance.