The China NMPA Approves Selpercatinib for the Treatment of Patients with RET-driven Lung and Thyroid Cancers

ROCKVILLE, Md. and SUZHOU, China , Oct. 9, 2022 /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, ophthalmology and other major diseases, is pleased to see that the National Medical Products Administration (NMPA) of China has approved the New Drug Application (NDA) for selpercatinib (40mg & 80mg capsules) for the treatment of adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with a rearranged during transfection (RET) gene fusion, adult and pediatric patients 12 years of age and older with advanced or metastatic medullary thyroid cancer (MTC) with a RET mutation who require systemic therapy, and adult and pediatric patients 12 years of age and older with advanced or metastatic thyroid cancer (TC) with a RET gene fusion who require systemic therapy and who are radioactive iodine-refractory (if radioactive iodine is appropriate).

Selpercatinib is a selective and potent RET kinase inhibitor that was discovered and developed by Eli Lilly and Company. In March 2022, Innovent and Lilly expanded their strategic partnership in oncology, which includes an agreement for Innovent to obtain the sole commercialization rights of selpercatinib once approved in China, positioning Innovent to be fully responsible for the pricing, importation, marketing, distribution and detailing of this product. With this further expanded oncology product portfolio, Innovent intends to use its experienced oncology commercial team to leverage its broad commercial coverage in hospitals and pharmacies at various tiers and to provide integrated patient solutions with strong synergies to cancer patients in China.

Selpercatinib was globally the first RET inhibitor granted accelerated approval by the FDA in May 2020,^[1] under the brand name Retevmo^®. In November 2021, the NDA for selpercatinib was accepted by the Center for Drug Evaluation (CDE) of NMPA in China and was granted priority review to expedite the review process. The NDA approval was based on data from the global LIBRETTO-001 study and data from the Chinese patient population in the LIBRETTO-321 study.

Selpercatinib was evaluated in the Phase I/II LIBRETTO-001 study, the largest clinical trial ever reported in patients with RET-driven cancers. The major efficacy outcome measures were confirmed overall response rate (ORR) and duration of response (DoR). The updated results of patients with NSCLC and medullary thyroid cancer were presented at the European Lung Cancer Congress (ELCC) 2022^[2] and the European Society for Medical Oncology (ESMO) Congress 2022,^[3] respectively.

Selpercatinib demonstrated potent and durable antitumor activity with a favorable safety profile in patients with locally advanced or metastatic RET fusion-positive NSCLC, advanced or metastatic RET-mutant MTC and advanced RET fusion-positive TC.

Ÿ In patients with NSCLC, the IRC-assessed ORR was 84.1% (95% CI:73, 92), median DoR was 20.2 months (95% CI:13, NE), median PFS was 22 months（95% CI:14, NE). Pre-treated patients (N=247) achieved an ORR of 61.1% (95% CI:55, 67), with a median DoR of 28.6 months (95% CI:20, NE) and a median PFS of 24.9 months (95% CI:19, NE).^[2]

Ÿ In cabozantinib/vandetanib (cab/van) naïve patients (N=142) and cab and/or van pre-treated patients with MTC (N=151), IRC-assessed ORRs were 81.0% and 73.5%, respectively. Despite a median follow-up of ∼2 yrs, DoR and PFS data are still immature, with response ongoing in most naïve patients. Pre-treated patients achieved a median PFS of 34 months (95% CI:26, NE) and DoR has not been reached yet.^[3]

Ÿ In naïve patients with TC (N=12), the IRC-assessed ORR was 92% (95% CI:62, 100), median DoR was NE (95% CI:15, NE), PFS in 1 year was 100% (95% CI:100, 100).^[3],[4] In pre-treated patients with TC (N=22), the IRC-assessed ORR was 77% (95% CI:55,92), median DoR was 18 months (95% CI:10, NE), PFS in one year was 69% (95% CI:43, 85).^[4]

Ÿ Selpercatinib was well-tolerated with most adverse events (AE) being low grade which are manageable and reversible. Three to four percent of patients discontinued treatment due to treatment-related AEs.^[2]-[4]

LIBRETTO-321 study^[5],[6] is an open-label, multicenter, Phase II study to assess the safety and efficacy of selpercatinib in participants in China with RET fusion-positive solid tumors. Of the 77 enrolled patients, 47 had RET fusion-positive NSCLC, 29 had RET-mutant MTC and one had RET fusion-positive TC. The results have been published in Therapeutic Advances in Medical Oncology in July^[5] (NSCLC part) and in August^[6] (MTC/TC part) in 2022.

The safety and efficacy profile of selpercatinib in the Chinese population was consistent with that observed in previously reported global studies.

Ÿ After 9.7 months of median follow-up, IRC-assessed ORR in the primary analysis set (PAS) of patients with NSCLC (N = 26) was 69.2% (95% CI:48.2, 85.7) and 94.4% of responses were ongoing; the ORR was 87.5% and 61.1% in treatment-naïve and pre-treated patients, respectively.^[5]

Ÿ After 8.7 months of median follow-up, IRC-assessed ORR in the PAS of patients with MTC (N = 26) was 57.7% (95% CI:36.9, 76.6) and 93.3% of responses were ongoing; the ORR was 58.8% (95% CI:32.9, 81.6) and 55.6% (95% CI:21.2, 86.3) in treatment-naïve and pre-treated patients, respectively.^[6]

Ÿ One treatment-naïve patient with TC was treated for 23.4 weeks and achieved a confirmed partial response (PR) at week eight. A maximum tumor burden shrinkage of 43% was determined by the IRC and the response was ongoing at cutoff.^[6]

Ÿ Selpercatinib was well-tolerated with most adverse events (AE) being low grades which are manageable and reversible. Three (3.9%) patients discontinued therapy due to treatment-related AEs.^[5],[6]

Professor Shun Lu from Shanghai Chest Hospital of Shanghai Jiao Tong University stated, "RET is a relatively rare target for NSCLC in the context of the high prevalence of NSCLC in China's patient population, but there exists a certain absolute base of patients whose survival status is equally noteworthy. Selpercatinib demonstrated efficacy in treating patients with RET fusion-positive NSCLC in the global LIBRETTO-001 Phase I/II clinical study, with a median PFS of about two years.^[2] The LIBRETTO-321 study further showed that selpercatinib significantly improved the efficacy of Chinese patients with advanced RET fusion-positive NSCLC, including patients with brain metastases, and the response was clinically meaningful and durable.^[5] We are thrilled that the approval will bring new treatment options to Chinese patients with RET fusion-positive NSCLC."

Professor Cheng Ying from Jilin Cancer Hospital stated, "The current global incidence of RET fusions in NSCLC patients is 1% to 2%, and the incidence of RET fusion NSCLC in China is 1.4%.^[7],[8] In the past, there have been limited therapies available for RET fusion-positive NSCLC to achieve satisfactory efficacy. In recent years, the introduction of RET inhibitors has opened a new era of therapy for such patients. As observed in the LIBRETTO-321 study, the ORR of selpercatinib in naïve and pre-treated patients in the Chinese population is very exciting. In addition, selpercatinib has also shown antitumor activity against brain lesions in preclinical models.^[5] We believe that the approval of selpercatinib in China will bring more survival benefits to Chinese patients with RET fusion-positive NSCLC."

Professor Ming Gao from Tianjin People Hospital stated, "RET alterations are oncogenic drivers in thyroid cancer, mostly seen in MTC. Selpercatinib is a highly selective and potent RET kinase inhibitor. In the LIBRETTO-001 study, the largest clinical trial ever reported in patients with RET-driven cancers, selpercatinib demonstrated clinically meaningful and durable responses in RET-altered thyroid cancer.^[6] The LIBRETTO-321 study has further demonstrated that the safety and efficacy profile of selpercatinib in the Chinese population was consistent with that observed in a previously reported global study. Its approval is undoubtedly a breakthrough milestone, and we hope more TC patients in China will benefit from it in the future."

Dr. Yongjun Liu, President of Innovent, stated, "Globally, selpercatinib is the first RET inhibitor approved and we are pleased to see its strong and durable response in line with good tolerability in clinical studies. This approval marks another milestone in mainland China for targeted therapies and will bring a new treatment option with high quality to RET fusion-positive cancer patients in China. For Innovent, the addition of a high-value commercialized product in our TKI BU will further enhance the synergistic value in the pipeline portfolio as well as our franchise in certain cancer types. We are committed to the partnership with Lilly to accelerate the launch of innovative medicines to benefit more cancer patients in China as soon as possible."

About RET-driven Cancers

Genomic alterations in the RET kinase, which include fusions and activating point mutations, lead to overactive RET signaling and uncontrolled cell growth. RET fusions have been identified in approximately 1-2% of NSCLC;^[9] and 10-20% of papillary thyroid cancers.^[10] Activating RET point mutations account for approximately 60% of sporadic MTC and approximately 90% of familial MTC.^[11] RET fusion-positive cancers and RET-mutant MTC are primarily dependent on this single activated kinase for their proliferation and survival. This dependency, often referred to as "oncogene addiction," renders such tumors highly susceptible to small molecule inhibitors targeting RET. Activating RET alterations are predominantly mutually exclusive from other oncogenic drivers.

About Non-Small Cell Lung Cancer (NSCLC）

Lung cancer is the leading cause of cancer death and the most commonly diagnosed tumor type in China with an overall five year survival rate of less than 15%.^[12] Non-small cell lung cancer (NSCLC) accounts for about 80% to 85% of all lung cancer. RET fusions have been identified in about 1.4% of Chinese patients with NSCLC and the incident cases are above 10,000 every year.⁸ Up to 50% of patients with RET fusion-positive NSCLC can have tumors that metastasize to the brain.^[13]

About Thyroid Cancer (TC)

Thyroid cancer is a cancer that starts in a person's thyroid gland. The most common types of thyroid cancer are papillary and follicular. Other types include Hurthle cell, medullary and anaplastic. Studies show that the positive rate of RET fusion in the Chinese TC patient population is about 6.03% with about 3,484 new cases each year in China;^[14] the positive rate of RET mutations in the Chinese sporadic MTC and familial MTC are approximately 42% and 88.8%, respectively, with about 1,795 new cases each year in China.^[15]

About Selpercatinib

Selpercatinib is a selective and potent RET kinase inhibitor with CNS activity. In the U.S., selpercatinib was approved by the FDA in May 2020, under the brand name Retevmo, as the first therapy specifically indicated for the treatment of adult patients with metastatic RET fusion-positive non-small cell lung cancer (NSCLC), adult and pediatric patients 12 years of age and older with advanced or metastatic RET-mutant medullary thyroid cancer (MTC) who require systemic therapy, and adult and pediatric patients 12 years of age and older with advanced or metastatic RET fusion-positive thyroid cancer who require systemic therapy and who are radioactive iodine-refractory (if radioactive iodine is appropriate). In Sep 2022, the FDA granted an accelerated approval for a tumor-agnostic indication for selpercatinib in adult patients with locally advanced or metastatic solid tumors with a RET gene fusion that have progressed on or following prior systemic treatment or who have no satisfactory alternative treatment options. Selpercatinib, is the first and only RET inhibitor to get this indication. In addition to the tumor-agnostic approval, the FDA has granted traditional approval for Retevmo in adult patients with locally advanced or metastatic RET fusion-positive non-small cell lung cancer (NSCLC).

About Innovent's strategic cooperation with Eli Lilly and Company

Innovent entered into a strategic collaboration with Lilly focusing on biological medicine in March 2015 – a groundbreaking partnership between a Chinese pharmaceutical company and a multinational pharmaceutical company. Under the agreement, Lilly and Innovent will co-develop and commercialize oncology medicines, including TYVYT^® (sintilimab injection) in China. In October 2015, the two companies announced the extension of their existing collaboration to include co-development of three additional oncology antibodies targeting oncology indications. In August 2019, Innovent further entered into a licensing agreement with Lilly to develop and commercialize a potentially global best-in-class diabetes medicine in China. This collaboration with Lilly indicates that Innovent has established a comprehensive level of cooperation between China's innovative pharmaceuticals sector and the international pharmaceuticals sector in fields such as R&D, CMC, clinical development and commercialization. In August 2020，Lilly and Innovent announced a global expansion of their strategic alliance for sintilimab, whereby Lilly obtained an exclusive license for sintilimab for geographies outside of China and plans to pursue registration of sintilimab in the U.S. and other geographies outside of China. In March 2022, Lilly and Innovent entered into a fifth agreement to expand its strategic partnership in oncology, in which Innovent obtained the sole commercialization rights to import, market, promote, distribute and detail CYRAMZA^® (ramucirumab) and selpercatinib once approved in Mainland China, and a right of first negotiation for potential future commercialization of pirtobrutinib in Mainland China.

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, ophthalmology and other major diseases. On Oct. 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 34 valuable assets in the fields of cancer, metabolic, autoimmune disease and other major therapeutic areas, with 8 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), olverembatinib (BCR ABL TKI), CYRAMZA^® (ramucirumab) and selpercatinib, 2 assets under NMPA NDA review, 4 assets in Phase 3 or pivotal clinical trials, and an additional 20 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, Sanofi, Adimab, Incyte, MD Anderson Cancer Center 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.
CYRAMZA^® (ramucirumab, Eli Lilly). CYRAMZA^® was discovered by Eli Lilly and licensed to Innovent for commercialization in Mainland China.

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.

References

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