Innovent Announces NMPA of China Acceptance of a Supplemental New Drug Application for TYVYT® (Sintilimab Injection plus Bevacizumab Biosimilar Injection and Chemotherapy in Patients with EGFR-mutated Non-squamous Non-small Cell Lung Cancer who Progressed after EGFR-TKI Therapy

Rhea-AI Summary

Innovent Biologics announced that the National Medical Products Administration of China accepted its supplemental New Drug Application for sintilimab plus bevacizumab biosimilar injection and chemotherapy for EGFR-mutated non-squamous non-small cell lung cancer (nsqNSCLC) patients who have progressed after EGFR-TKI therapy. This decision follows a Phase 3 clinical trial (ORIENT-31) showing significant improvement in progression-free survival for patients treated with sintilimab in combination with bevacizumab and chemotherapy. The safety profile remains consistent with prior studies.

Positive

• sNDA acceptance by NMPA for sintilimab plus bevacizumab biosimilar in nsqNSCLC.
• Phase 3 trial showed significant improvement in progression-free survival.
• No new safety signals reported, consistent with previous studies.

Negative

• None.

SAN FRANCISCO and SUZHOU, China, Dec. 24, 2021 /PRNewswire/ -- Innovent Biologics, Inc. (Innovent) (HKEX: 01801), a world-class biopharmaceutical company that develops, manufactures and commercializes high quality medicines for the treatment of cancer, metabolic, autoimmune and other major diseases, today announced that the National Medical Products Administration (NMPA) of China has accepted the supplemental New Drug Application (sNDA) for sintilimab plus bevacizumab biosimilar injection and chemotherapy in patients with EGFR-mutated non-squamous non-small cell lung-cancer (nsqNSCLC) who progressed after EGFR-TKI therapy.

The sNDA is based on the first interim analysis of ORIENT-31, the randomized, double-blind, multi-center Phase 3 clinical trial – which evaluated sintilimab in combination with or without bevacizumab biosimilar and chemotherapy compared to placebo in combination with chemotherapy for patients with EGFR-mutated nsqNSCLC who had disease progression after EGFR-TKI therapy. Based on the first interim analysis conducted by the Independent Data Monitoring Committee (IDMC), Arm A (sintilimab in combination with bevacizumab and chemotherapy) demonstrated a statistically significant improvement in the primary endpoint of IRRC-assessed progression-free survival (PFS) compared to Arm C (placebo in combination with chemotherapy). Additionally, key secondary endpoints of objective response rate (ORR) and duration of response (DOR) were improved in Arm A compared with Arm C, which was immature yet. A numerical improvement of IRRC-assessed PFS of Arm A compared to Arm B (sintilimab and chemotherapy combination) was observed, while a trend of PFS benefit was also observed in Arm B versus Arm C, though data was immature yet. The safety profile was consistent with that observed in previously reported studies of sintilimab and bevacizumab biosimilar, without new or unexpected safety signals. The combination of sintilimab and chemotherapy with or without bevacizumab biosimilar was well tolerated. The results of ORIENT-31 had been reported as an oral presentation at the European Society for Medical Oncology (ESMO) Virtual Plenary 2021 in November.

The principal investigator of the ORIENT-31 study, Prof. Shun Lu from the Oncology Department of Shanghai Chest Hospital, stated, "In China, the incidence and mortality of lung cancer ranks top among all malignancies, and about 40%-50% nsqNSCLC patients have an EGFR mutation. The standard first-line treatment for patients with advanced EGFR-mutated nsqNSCLC is EGFR-TKI therapy. However, the therapeutic options after progression on EGFR-TKI are limited, representing a large unmet medical need. ORIENT-31 was the first prospective, double-blind Phase 3 study globally to demonstrate the PFS benefit of immunotherapy in combination with antiangiogenic agents and chemotherapy in patients with EGFR-mutated nsqNSCLC who progressed after EGFR-TKI therapy."

Dr. Hui Zhou, Senior Vice President of Innovent, stated, "While immunotherapy has been approved for treatment of many malignancies, it has not yet been proven to be sufficiently efficacious for oncogene driven cancers. The acceptance of this sNDA by China's NMPA represents an important milestone in demonstrating the potential value of sintilimab plus bevacizumab and chemotherapy in patients with EGFR-mutated nsqNSCLC who progressed after EGFR-TKI therapy. We look forward to working with the China regulatory authorities on the sNDA review and we hope to bring the new regimen to patients with EGFR-mutated nsqNSCLC who progressed after EGFR-TKI therapy as quickly as possible."

About Non-Squamous Non-Small Cell Lung Cancer (NSCLC)

Lung cancer is the leading cause of cancer death worldwide and the second most commonly diagnosed tumor type. Non-small cell lung cancer (NSCLC) accounts for about 80% to 85% of all lung cancer, in which about 70% of NSCLC patients present with locally advanced or metastatic disease that is not suitable for surgical resection at diagnosis. In China, nsqNSCLC accounts for 70% of NSCLC, in which about 40% to 50% of nsqNSCLC patients have an EGFR mutation. The standard first-line treatment for patients with advanced EGFR-mutated NSCLC is a third generation EGFR TKI, or first or second generation EGFR TKI. For patients who have progressed following EGFR-TKI treatment, platinum-based chemotherapy is still the standard therapy with limited benefit, representing a large unmet medical need.

About the ORIENT-31 Study

ORIENT-31 is a randomized, double-blind, multi-center Phase 3 clinical study conducted in China evaluating sintilimab, with or without bevacizumab biosimilar, combined with chemotherapy (pemetrexed and cisplatin) in patients with EGFR-mutated locally advanced or metastatic nsqNSCLC who have progressed following EGFR TKI treatment (ClinicalTrials.gov, NCT003802240). The primary endpoint is PFS as assessed by BIRRC based on RECIST v1.1. The secondary endpoints include overall survival (OS), PFS as assessed by investigators, ORR and safety.

Eligible patients included: patients with disease progression following first or second generation EGFR TKI and confirmed as T790M negative, or T790M positive but further progressed on third generation EGFR-TKI treatment, or patients with disease progression following third generation EGFR TKI as first line treatment.

Patients were randomized in a 1:1:1 ratio to receive sintilimab plus bevacizumab biosimilar combined with pemetrexed and cisplatin (Arm A), sintilimab plus placebo 2 combined with pemetrexed and cisplatin (Arm B), or placebo 1 plus placebo 2 combined with pemetrexed and cisplatin (Arm C). After 4 cycles of combination treatment, patients will receive maintenance treatment of sintilimab plus bevacizumab biosimilar and pemetrexed, sintilimab plus placebo 2 and pemetrexed, placebo 1 plus placebo 2 and pemetrexed, until radiographic disease progression, unacceptable toxicity or any other conditions that required treatment discontinuation. Target accrual is 480 patients. By the data cutoff date of the first interim analysis, 444 patients were enrolled.

About Sintilimab

Sintilimab, marketed as TYVYT^® (sintilimab injection) in China, is an innovative PD-1 inhibitor with global quality standards jointly developed by Innovent and Eli Lilly and Company. Sintilimab is an 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. Innovent is currently conducting more than 20 clinical studies of sintilimab worldwide, to evaluate its safety and efficacy in a wide variety of cancer indications, including more than 10 registrational or pivotal clinical trials.

In China, sintilimab has been approved and included in the National Reimbursement Drug List (NRDL) for four indications, including:

• The treatment of relapsed or refractory classic Hodgkin's lymphoma after two lines or later of systemic chemotherapy;
• In combination with pemetrexed and platinum chemotherapy, for the first-line treatment of non-squamous non-small cell lung cancer;
• In combination with gemcitabine and platinum chemotherapy, for the first-line treatment of squamous non-small cell lung cancer;
• In combination with BYVASDA^® (bevacizumab biosimilar injection) for the first-line treatment of unresectable or advanced hepatocellular carcinoma.

Additionally, sintilimab currently has three regulatory submissions accepted for review in NMPA, including:

• In combination with cisplatin plus paclitaxel or cisplatin plus 5-fluorouracil for the first-line treatment of esophageal squamous cell carcinoma;
• In combination with chemotherapy for the first-line treatment of unresectable, locally advanced, recurrent or metastatic gastric or gastroesophageal junction adenocarcinoma;
• In combination with bevacizumab biosimilar and chemotherapy for EGFR-mutated non-squamous NSCLC following EGFR-TKI treatment.

Additionally, two clinical studies of sintilimab have met their primary endpoints:

• Phase 2 study as second-line treatment of esophageal squamous cell carcinoma;
• Phase 3 study as second-line treatment for squamous NSCLC with disease progression following platinum-based chemotherapy.

In May 2021, the U.S. FDA accepted for review the Biologics License Application (BLA) for sintilimab in combination with pemetrexed and platinum chemotherapy for the first-line treatment of non-squamous non-small cell lung cancer.

About BYVASDA^® (bevacizumab biosimilar injection)

BYVASDA^®, also known as IBI305, is a bevacizumab biosimilar and a recombinant humanized anti-VEGF monoclonal antibody drug. Vascular endothelial growth factor (VEGF) is an important factor in angiogenesis that is highly expressed by the endothelial cells in most human tumors. An anti-VEGF antibody binds VEGF-A selectively with high affinity and blocks its binding to VEGF-2 receptors on the surface of vascular endothelial cells, thereby inhibiting signaling pathways such as PI3K-Akt/PKB and Ras-Raf-MEK-ERK. BYVASDA^® produces anti-tumor effects by inhibiting the growth, proliferation and migration of vascular endothelial cells, blocking angiogenesis, reducing vascular permeability, blocking blood supply to tumor tissues, inhibiting the proliferation and metastasis of tumor cells and inducing apoptosis in tumor cells. Since its launch, bevacizumab has been approved for the treatment of patients with multiple malignant tumors globally, including non-small cell lung cancer, metastatic colorectal cancer, glioblastoma, renal cell carcinoma, cervical cancer, and epithelial ovarian, fallopian tube, or primary peritoneal cancer. The efficacy and safety of bevacizumab in these tumor types have been well recognized worldwide.

In China, BYVASDA^® (bevacizumab biosimilar injection) is approved for indications including advanced non-small cell lung cancer, metastatic colorectal cancer, adult recurrent glioblastoma, and advanced or unresectable hepatocellular carcinoma.

About Innovent

Inspired by the spirit of "Start with Integrity, Succeed through Action,"  Innovent's mission is to develop, manufacture and commercialize high-quality biopharmaceutical products that are affordable to ordinary people. Established in 2011, Innovent is committed to developing, manufacturing and commercializing high-quality innovative medicines for the treatment of cancer, autoimmune, metabolic and other major diseases. On October 31, 2018, Innovent was listed on the Main Board of the Stock Exchange of Hong Kong Limited with the stock code: 01801.HK.

Since its inception, Innovent has developed a fully integrated multi-functional platform which includes R&D, CMC (Chemistry, Manufacturing, and Controls), clinical development and commercialization capabilities. Leveraging the platform, the company has built a robust pipeline of 26 valuable assets in the fields of cancer, metabolic, autoimmune disease and other major therapeutic areas, with 6 products approved for marketing in China – TYVYT^® (sintilimab injection), BYVASDA^® (bevacizumab biosimilar injection), SULINNO^® (adalimumab biosimilar injection), HALPRYZA^® (rituximab biosimilar injection) , Pemazyre^® (pemigatinib oral inhibitor) and olverembatinib (BCR ABL TKI), a Biologics License Application (BLA) for sintilimab accepted for review in the U.S., 5 assets in Phase 3 or pivotal clinical trials, and an additional 15 molecules in clinical studies.

Innovent has built an international team with advanced talent in high-end biological drug development and commercialization, including many global experts. The company has also entered into strategic collaborations with Eli Lilly and Company, Adimab, Incyte, MD Anderson Cancer Center, Hanmi and other international partners. Innovent strives to work with many collaborators to help advance China's biopharmaceutical industry, improve drug availability and enhance the quality of the patients' lives. For more information, please visit: www.innoventbio.com. and www.linkedin.com/company/innovent-biologics/.

Note:

TYVYT^® (sintilimab injection) is not an approved product in the United States.
BYVASDA^® (bevacizumab biosimilar injection), SULINNO^®, and HALPRYZA^® (rituximab biosimilar injection) are not approved products in the United States.
TYVYT^® (sintilimab injection, Innovent)
BYVASDA^® (bevacizumab biosimilar injection, Innovent)
HALPRYZA^® (rituximab biosimilar injection, Innovent)
SULINNO^® (adalimumab biosimilar injection, Innovent)
Pemazyre^® (pemigatinib oral inhibitor, Incyte Corporation). Pemazyre^® was discovered by Incyte Corporation and licensed to Innovent for development and commercialization in Mainland China, Hong Kong, Macau and Taiwan.

Disclaimer:

1. This indication is still under clinical study, which hasn't been approved in China.
2. Innovent does not recommend any off-label usage.
3. For medical and healthcare professionals only.

Forward-Looking Statements

This news release may contain certain forward-looking statements that are, by their nature, subject to significant risks and uncertainties. The words "anticipate", "believe", "estimate", "expect", "intend" and similar expressions, as they relate to Innovent, are intended to identify certain of such forward-looking statements. Innovent does not intend to update these forward-looking statements regularly.

These forward-looking statements are based on the existing beliefs, assumptions, expectations, estimates, projections and understandings of the management of Innovent with respect to future events at the time these statements are made. These statements are not a guarantee of future developments and are subject to risks, uncertainties and other factors, some of which are beyond Innovent's control and are difficult to predict. Consequently, actual results may differ materially from information contained in the forward-looking statements as a result of future changes or developments in our business, Innovent's competitive environment and political, economic, legal and social conditions.

Innovent, the Directors and the employees of Innovent assume (a) no obligation to correct or update the forward-looking statements contained in this site; and (b) no liability in the event that any of the forward-looking statements does not materialize or turn out to be incorrect.

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SOURCE Innovent Biologics

FAQ

What is the recent significant announcement from Innovent Biologics regarding sintilimab?

Innovent Biologics announced the acceptance of a supplemental New Drug Application for sintilimab plus bevacizumab biosimilar and chemotherapy in EGFR-mutated non-squamous non-small cell lung cancer.

What clinical trial data supported the sNDA for IVBIY?

The sNDA is based on the ORIENT-31 Phase 3 trial, which showed a statistically significant improvement in progression-free survival for the treatment combination.

What type of cancer does sintilimab target?

Sintilimab is indicated for EGFR-mutated non-squamous non-small cell lung cancer (nsqNSCLC) patients.

How has the safety of sintilimab been characterized in recent studies?

The safety profile of sintilimab in recent studies, including ORIENT-31, remained consistent with earlier reports, with no new safety signals.