Date: 25-Apr-2020

China NMPA Accepts Innovent, Eli Lilly’s SNDA For Sintilimab In Combo With Alimta And Platinum To Treat Non-squamous NSCLC

Innovent Biologics Inc, a world-class biopharmaceutical company that develops, manufactures and commercializes high quality medicines for the treatment of oncology, autoimmune, metabolic and other major diseases, jointly announced with Eli Lilly and Company that the National Medical Products Administration (NMPA) of China has accepted the supplemental New Drug Application (sNDA) for Tyvyt (sintilimab injection) in combination with Alimta (pemetrexed) and platinum as first-line therapy in non-squamous non-small cell lung cancer (nsqNSCLC). 

Tyvyt was officially approved by the NMPA in December 2018 for the treatment of relapsed or refractory classical Hodgkin's lymphoma after at least two lines of systemic chemotherapy, and has been the only anti-PD-1 monoclonal antibody included in the New Catalogue of the National Reimbursement Drug List (NRDL) since November 2019.

The NDA was based on the pre-specified interim analysis of a randomized, double-blind, phase 3 clinical trial (ORIENT-11)—Tyvyt (sintilimab injection) or placebo in combination with Alimta and platinum as first-line therapy for advanced or recurrent nsqNSCLC without sensitizing EGFR mutation or ALK rearrangement.

Based on the interim analysis conducted by the Independent Data Monitoring Committee (IDMC), Tyvyt in combination with Alimta and platinum demonstrated a statistically significant improvement in progression-free survival (PFS) compared with placebo in combination with Alimta and platinum, which met the pre-defined efficacy criteria. After a median follow up of 8.9 months, the median PFS of the experimental group and the control group assessed by Independent Radiographic Review Committee was 8.9 months and 5.0 months respectively, HR (95%CI) = 0.482 (0.362,0.643), P < 0.00001.

The safety profile is consistent with previously reported sintilimab studies, and no new safety signals were identified. Detailed data will be released in an upcoming international academic conference and journal.

Professor Li ZHANG, head of Department of Internal Medicine, Sun Yat-sen University Cancer Center, the primary investigator of ORIENT-11 study stated, "Nearly half of Chinese nsqNSCLC patients lack sensitizing EGFR mutation or ALK rearrangement, which makes them do not respond to targeted therapy.  ORIENT-11 study has demonstrated a significant delay of disease progression brought by sintilimab in combination with chemotherapy in this patient population."

Dr. Hui ZHOU, vice president of Medical Science and Strategy Oncology of Innovent stated, "The morbidity and mortality of lung cancer both rank first among all types of cancers in China. Despite treatment advances, there remains significant unmet needs for additional effective treatment options for lung cancer patients. The acceptance of NDA by the NMPA represents an important progress in demonstrating the potential value of Tyvyt in lung cancer. We will actively cooperate with the regulatory authority to bring the high quality therapy to more patients with advanced non-squamous NSCLC as soon as possible."

"The intention of Lilly's strategic cooperation with Innovent is to bring new anti-tumor treatments, developed with global standards, to patients in China. As the success of this partnership, Tyvyt is the only anti-PD-1 monoclonal antibody included in the NRDL for relapsed or refractory classical Hodgkin's lymphoma," said Dr. Li WANG, senior vice-president of Lilly China and head of Lilly China Drug Development and Medical Affairs. "With the encouraging result of ORIENT-11, Tyvyt may soon expand its indication to lung cancer. In the future, we will strengthen cooperation with Innovent to further explore Tyvyt's potential in the field of immuno-oncology therapy and how Tyvyt may bring benefits to more patients."

ORIENT-11 is a randomized, double-blind, phase 3 clinical trial to evaluate the efficacy and safety of Tyvyt (sintilimab injection) or placebo in combination with Alimta (pemetrexed) and platinum as first-line therapy for advanced or recurrent nsqNSCLC without sensitizing EGFR mutation or ALK rearrangement. The primary endpoint is progression-free survival (PFS) assessed by Independent Radiographic Review Committee based on RECIST v1.1. The key secondary endpoints include overall survival (OS) and safety profile.

A total of 397 subjects have been enrolled in ORIENT-11 trial and randomized in a 2:1 ratio to receive either sintilimab 200mg or placebo in combination with Alimta (pemetrexed) and platinum every 3 weeks for up to 4 cycles, followed by either sintilimab or placebo plus ALIMTA maintenance therapy. The subjects will receive treatment until radiographic disease progression, unacceptable toxicity or any other conditions that require treatment discontinuation. Conditional crossover is permitted.

Lung cancer is a malignancy with the highest morbidity and mortality in China. NSCLC accounts for about 80 percent to 85 percent of lung cancer. Approximately 70 per cent of NSCLC are locally advanced or metastatic at initial diagnosis, rendering the patients with no chance of radical resection. Meanwhile, even after radical surgery patients still have a high chance of recurrence and eventually die from disease progression. About 70 per cent of NSCLC in China are non-squamous subtype and 50 per cent of nsqNSCLC are without sensitizing EGFR mutation or ALK rearrangement. These patients do not respond well to targeted therapy and there are limited treatment options available to them.

Tyvyt (sintilimab injection), an innovative drug developed with global quality standards jointly developed in China by Innovent and Lilly, has been granted marketing approval by the NMPA for relapsed or refractory classic Hodgkin's lymphoma after at least two lines of systemic chemotherapy, and included in the 2019 Guidelines of Chinese Society of Clinical Oncology for Lymphoid Malignancies. Tyvyt is the only PD-1 inhibitor that has been included in the new Catalogue of the National Reimbursement Drug List (NRDL) in November 2019.

Tyvyt is a type of immunoglobulin G4 monoclonal antibody, which binds to PD-1 molecules on the surface of T-cells, blocks the PD-1/ PD-Ligand 1 (PD-L1) pathway and reactivates T-cells to kill cancer cells.