RegulationOrphan Drug (US), Orphan Drug (EU), Priority Review (CN), Breakthrough Therapy (CN), Special Review Project (CN), Orphan Drug (KR), National Science and Technology Major Project (CN)

Structure

Molecular FormulaC25H27N5O4S

InChIKeyFYJROXRIVQPKRY-UHFFFAOYSA-N

CAS Registry1218779-75-9

834

Clinical Trials associated with Apatinib Mesylate

NCT06188455 / Not yet recruitingPhase 3IIT

Clinical Study of Fluzopalil Combined With Apatinib for Maintenance Therapy After Platinum-containing Chemotherapy in Patients With Recurrent Ovarian Cancer

Thirty-seven women aged 18-75 years with recurrent ovarian cancer were enrolled

Start Date01 Dec 2024

Sponsor / Collaborator

The First Affiliated Hospital of Xiamen University

NCT06308575 / Not yet recruitingPhase 2

A Phase II Study of Rivoceranib for Patients With Recurrent or Metastatic Olfactory Neuroblastoma

To learn if rivoceranib can help to control olfactory neuroblastoma. The safety of this drug in participants with olfactory neuroblastoma will also be studied.

Start Date30 Sep 2024

Sponsor / Collaborator

Elevar Therapeutics, Inc.

NCT06415669 / RecruitingPhase 2IIT

A Study of Paclitaxel (Albumin-bound) Combined With Apatinib and Adebrelimab in the Treatment of Locally Advanced or Metastatic Gastric/Gastroesophageal Junction Adenocarcinoma Following Previous Immunotherapy Progression

To evaluate the initial efficacy and safety of paclitaxel for injection (albumin-bound) in combination with apatinib mesylate and adebrelimab in the treatment of locally advanced or metastatic gastric/gastroesophageal junction adenocarcinoma following the progression of previous immunotherapy.

Start Date19 May 2024

Sponsor / Collaborator

The First Affiliated Hospital of Xiamen University

100 Clinical Results associated with Apatinib Mesylate

100 Translational Medicine associated with Apatinib Mesylate

100 Patents (Medical) associated with Apatinib Mesylate

1,202

Literatures (Medical) associated with Apatinib Mesylate

01 May 2024·Recent patents on anti-cancer drug discovery

A Synergistic Combination of Oleanolic Acid and Apatinib to Enhance Antitumor Effect on Liver Cancer Cells and Protect against Hepatic Injury

Article

Author: Cui, Qingrong ; Raza, Faisal ; Ren, Juan ; Wan, Haopeng ; Li, Haiyang ; Zafar, Hajra ; Wang, Xiangqi ; Chen, Xue ; Yan, Jun

Background::

As a pentacyclic triterpenoid, OA (oleanolic acid) has exhibited antiinflammatory, immunomodulatory and antitumor effects. VEGFR-2 (vascular endothelial cells receptor-2) tyrosine kinase activity could be inhibited by apatinib, a small-molecule antiangiogenic agent.

Objective::

Thus, this study sought to investigate the mechanism underlying the synergistic antitumor activity of combined OA and apatinib patent.

Methods::

Through CCK8 (Cell counting kit 8 assay), flow cytometric and western blotting techniques, we conducted in vitro studies on apatinib and OA effects on cell proliferation and apoptosis in H22 cell line. H22 tumor-burdened mice model was established in vivo, while the related signaling pathways were studied via pathological examination, western blotting and qPCR (quantitative polymerase chain reaction).

Results::

Growth of H22 cells in vitro and in vivo could be inhibited effectively by apatinib and OA. Thus, OA repaired liver function and inhibited oxidative stress induced by apatinib.

Conclusion::

OA can treat apatinib induced liver injury in H22 Tumor-burdened mice by enhancing the suppresssive effect of apatinib on the growth of tumor.

01 Mar 2024·Toxicology in vitro : an international journal published in association with BIBRA

Inhibitory effects of the main metabolites of Apatinib on CYP450 isozymes in human and rat liver microsomes

Article

Author: Chen, Zhe ; Zhang, Bo-Wen ; Pang, Ni-Hong ; Xu, Ren-Ai ; Hu, Guo-Xin ; Chen, Lian-Guo

PURPOSE:

The inhibitory effect of Apatinib on cytochrome P450 (CYP450) enzymes has been studied. However, it is unknown whether the inhibition is related to the major metabolites, M1-1, M1-2 and M1-6.

METHODS:

A 5-in-1 cocktail system composed of CYP2B6/Cyp2b1, CYP2C9/Cyp2c11, CYP2E1/Cyp2e1, CYP2D6/Cyp2d1 and CYP3A/Cyp3a2 was used in this study. Firstly, the effects of APA and its main metabolites on the activities of HLMs, RLMs and recombinant isoforms were examined. The reaction mixture included HLMs, RLMs or recombinant isoforms (CYP3A4.1, CYP2D6.1, CYP2D6.10 or CYP2C9.1), analyte (APA, M1-1, M1-2 or M1-6), probe substrates. The reactions were pre-incubated for 5 min at 37 °C, followed by the addition of NAPDH to initiate the reactions, which continued for 40 min. Secondly, IC₅₀ experiments were conducted to determine if the inhibitions were reversible. The reaction mixture of the "+ NADPH Group" included HLMs or RLMs, 0 to 100 of μM M1-1 or M1-2, probe substrates. The reactions were pre-incubated for 5 min at 37 °C, and then NAPDH was added to initiate reactions, which proceeded for 40 min. The reaction mixture of the "- NADPH Group" included HLMs or RLMs, probe substrates, NAPDH. The reactions were pre-incubated for 30 min at 37 °C, and then 0 to 100 μM of M1-1 or M1-2 was added to initiate the reactions, which proceeded for 40 min. Finally, the reversible inhibition of M1-1 and M1-2 on isozymes was determined. The reaction mixture included HLMs or RLMs, 0 to 10 μM of M1-1 or M1-2, probe substrates with concentrations ranging from 0.25K_m to 2K_m.

RESULTS:

Under the influence of M1-6, the activity of CYP2B6, 2C9, 2E1 and 3A4/5 was increased to 193.92%, 210.82%, 235.67% and 380.12% respectively; the activity of CYP2D6 was reduced to 92.61%. The inhibitory effects of M1-1 on CYP3A4/5 in HLMs and on Cyp2d1 in RLMs, as well as the effect of M1-2 on CYP3A in HLMs, were determined to be noncompetitive inhibition, with the K_i values equal to 1.340 μM, 1.151 μM and 1.829 μM, respectively. The inhibitory effect of M1-1 on CYP2B6 and CYP2D6 in HLMs, as well as the effect of M1-2 on CYP2C9 and CYP2D6 in HLMs, were determined to be competitive inhibition, with the K_i values equal to 12.280 μM, 2.046 μM, 0.560 μM and 4.377 μM, respectively. The inhibitory effects of M1-1 on CYP2C9 in HLMs and M1-2 on Cyp2d1 in RLMs were determined to be mixed-type, with the K_i values equal to 0.998 μM and 0.884 μM. The parameters could not be obtained due to the atypical kinetics of CYP2E1 in HLMs under the impact of M1-2.

CONCLUSIONS:

M1-1 and M1-2 exhibited inhibition for several CYP450 isozymes, especially CYP2B6, 2C9, 2D6 and 3A4/5. This observation may uncover potential drug-drug interactions and provide valuable insights for the clinical application of APA.

14 Feb 2024·ACS applied materials & interfaces

Biomimetic Responsive Nanoconverters with Immune Checkpoint Blockade Plus Antiangiogenesis for Advanced Hepatocellular Carcinoma Treatment

Article

Author: Liu, Jingfeng ; Zhong, Aoxue ; Liu, Xiaolong ; Li, Yonghao ; Zhang, Yuting ; Min, Juan ; Cao, Yanbing ; Fu, Jinghao ; Tu, Haibin ; Wang, Jianmin ; Yang, Yong ; Wu, Ming

The first-line treatment for advanced hepatocellular carcinoma (HCC) combines immune checkpoint inhibitors and antiangiogenesis agents to prolong patient survival. Nonetheless, this approach has several limitations, including stringent inclusion criteria and suboptimal response rates that stem from the severe off-tumor side effects and the unfavorable pharmacodynamics and pharmacokinetics of different drugs delivered systemically. Herein, we propose a single-agent smart nanomedicine-based approach that mimics the therapeutic schedule in a targeted and biocompatible manner to elicit robust antitumor immunity in advanced HCC. Our strategy employed pH-responsive carriers, poly(ethylene glycol)-poly(β-amino esters) amphiphilic block copolymer (PEG-PAEs), for delivering apatinib (an angiogenesis inhibitor), that were surface-coated with plasma membrane derived from engineered cells overexpressing PD-1 proteins (an immune checkpoint inhibitor to block PD-L1). In an advanced HCC mouse model with metastasis, these biomimetic responsive nanoconverters induced significant tumor regression (5/9), liver function recovery, and complete suppression of lung metastasis. Examination of the tumor microenvironment revealed an increased infiltration of immune effector cells (CD8⁺ and CD4⁺ T cells) and reduced immunosuppressive cells (myeloid-derived suppressor cells and T regulatory cells) in treated tumors. Importantly, our nanomedicine selectively accumulated in both small and large HCC occupying >50% of the liver volume to exert therapeutic effects with minimal systemic side effects. Overall, these findings highlight the potential of such multifunctional nanoconverters to effectively reshape the tumor microenvironment for advanced HCC treatment.

News (Medical) associated with Apatinib Mesylate

30 May 2024

·www.biospace.com

Elevar Therapeutics Reports Landmark Median Overall Survival of 23.8 Months in First-Line Treatment for Unresectable Hepatocellular Carcinoma

Phase 3 CARES-310 study found combination of camrelizumab and rivoceranib continued to show sustained long-term survival compared with sorafenib as a first-line treatment for uHCC Final analysis reported the longest median overall survival for any treatment in a global Phase 3 trial in uHCC Combination is the only uHCC therapy to increase median overall survival to approximately two years with greater than one in three patients alive at three years FORT LEE, N.J., May 30, 2024 (GLOBE NEWSWIRE) -- Elevar Therapeutics, Inc., a majority-owned subsidiary of HLB Co., Ltd., today announced the landmark overall survival (OS) analysis of camrelizumab and rivoceranib as a first-line treatment for unresectable hepatocellular carcinoma (uHCC) will be presented at an in-person poster presentation during the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting on June 1. The abstract can be viewed at asco.org/abstracts. “The CARES-310 final OS analysis confirmed statistically superior and clinically meaningful survival improvement with a manageable safety pro the combination of camrelizumab and rivoceranib as a first-line treatment for patients suffering from unresectable hepatocellular carcinoma,” said Saeho Chong, Elevar chief executive officer. “These data confirm that the novel combination therapy represents a clinically differentiated improvement to the standard of care in first-line treatments for uHCC.” “The CARES-310 landmark analysis reported the longest median overall survival for any treatment in a global Phase 3 trial in the uHCC setting,” said Ahmed Omar Kaseb, M.D., professor, Department of Gastrointestinal Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center. “The combination of camrelizumab and rivoceranib shows distinct promise to advance the standard of care for patients suffering with unresectable hepatocellular carcinoma.” The interim analysis of CARES-310 OS was completed after data cut-off on Feb. 8, 2022. For the final analysis, 16 months later, camrelizumab + rivoceranib continued to show clinically meaningful survival improvement compared with sorafenib, with manageable safety profile. The extended follow-up further confirmed the favorable benefit-to-risk pro camrelizumab + rivoceranib, supporting it as a potential new first-line treatment option for uHCC. In the final analysis, median OS was significantly prolonged with camrelizumab + rivoceranib vs. sorafenib (23.8 mo [95% CI 20.6-27.2] vs. 15.2 mo [95% CI 13.2-18.5]; hazard ratio 0.64 [95% CI 0.52-0.79]; 1-sided p < 0.0001). OS rate with camrelizumab + rivoceranib vs. sorafenib was 49.0% vs. 36.2% at 24 mo, and 37.7% vs. 24.8% at 36 mo. OS benefits with camrelizumab + rivoceranib were generally consistent across subgroups, regardless of geographical region, race and etiology. CARES-310 was the first trial to demonstrate significant progression-free survival (PFS) and overall survival benefits with immunotherapy plus an anti-angiogenic tyrosine kinase inhibitor (TKI) over standard TKI as first-line treatment for uHCC. ASCO 2024 CARES-310 Landmark Overall Survival In-Person Presentation The in-person poster presentation (abstract number 4110), titled “Camrelizumab plus rivoceranib vs sorafenib as first-line therapy for unresectable hepatocellular carcinoma (uHCC): Final overall survival analysis of the Phase 3 CARES-310 study,” will be presented June 1 from 1:30 p.m. to 4:30 p.m. CT during the poster session: Gastrointestinal Cancer—Gastroesophageal, Pancreatic, and Hepatobiliary. The abstract can be viewed at: asco.org/abstracts. Additional ASCO 2024 CARES-310 Online Publication Additional data from CARES-310 will be available as an online publication. Abstract number e16197 is titled: “Role of neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte-ratio (PLR) in unresectable hepatocellular carcinoma (uHCC): Subgroup analysis of patients treated with camrelizumab (cam) + rivoceranib (rivo) in the CARES-310 trial.” The abstract can be viewed at: asco.org/abstracts. About Hepatocellular Carcinoma (HCC) HCC is the most common type of primary liver cancer. It most frequently occurs in people with chronic liver diseases, such as cirrhosis caused by hepatitis B or hepatitis C infection. HCC typically has a poor prognosis and a lack of treatment options and is therefore a condition with an urgent medical need. About CARES-310 CARES-310 (NCT03764293) was a randomized, open-label, international Phase 3 study, which included 543 patients with unresectable or metastatic HCC who had not received prior systemic therapy. Patients were randomized 1:1 to receive the combination of camrelizumab + rivoceranib or sorafenib (400 mg orally twice daily), a standard-of-care first-line multi-kinase inhibitor treatment for uHCC. Camrelizumab was administered intravenously (190 mg) every two weeks and rivoceranib was administered orally (250 mg) once daily. The study was conducted at 95 study sites across 13 countries/regions, in which systemic treatment for uHCC independent of etiology, rivoceranib plus camrelizumab demonstrated statistically significant and clinically meaningful prolonged overall survival and progression-free survival, and improved overall response rate versus sorafenib. The co-primary endpoints were overall survival and progression-free survival. Secondary endpoints included objective response rate and duration of response. About Camrelizumab Camrelizumab (SHR-1210) is a humanized monoclonal antibody that binds to the programmed death-1 (PD-1) receptor. Blockade of the PD-1/PD-L1 signaling pathway is a therapeutic strategy showing success in a wide variety of solid and hematological cancers. Camrelizumab is developed by Hengrui Pharma and has been studied in more than 5,000 patients. Currently, 50 clinical trials are underway in a broad range of tumors (including liver cancer, lung cancer, gastric cancer, and breast cancer, etc.) and treatment settings. Camrelizumab, under the brand name AiRuiKa®, is currently approved for eight indications in China, including monotherapy for the treatment of HCC (second-line), in combination with rivoceranib as a treatment for uHCC (first-line), relapsed/refractory classic Hodgkin’s lymphoma (third-line), esophageal squamous cell carcinoma (second-line) and nasopharyngeal carcinoma (third-line or further) and in combination with chemotherapy for the treatment of non-small cell lung cancer (non-squamous and squamous), esophageal squamous cell carcinoma and nasopharyngeal carcinoma in the first-line setting. The U.S. Food and Drug Administration granted Orphan Drug Designation to camrelizumab for advanced HCC in April 2021. About Rivoceranib Rivoceranib, a small-molecule tyrosine kinase inhibitor (TKI), is a highly potent inhibitor of vascular endothelial growth factor receptor 2 (VEGFR-2), a primary pathway for tumor angiogenesis. VEGFR-2 inhibition is a clinically validated approach to limit tumor growth and disease progression. Rivoceranib is currently being studied as a monotherapy and in combination with chemotherapy and immunotherapy in various solid tumor indications. Ongoing clinical studies include uHCC (in combination with camrelizumab), gastric cancer (as a monotherapy and in combination with paclitaxel), adenoid cystic carcinoma (as a monotherapy) and colorectal cancer (in combination with Lonsurf®). Rivoceranib was the first TKI approved in gastric cancer in China (November 2014). It is also approved in China in combination with camrelizumab as a first-line treatment for uHCC (January 2023). The drug has been studied in more than 6,000 patients worldwide and was well tolerated in clinical trials with a comparable safety pro other TKIs and VEGF inhibitors. Orphan drug designations have been granted in gastric cancer (U.S., EU and South Korea), in adenoid cystic carcinoma (U.S.) and in uHCC (U.S.). Elevar Therapeutics, Inc. holds the global rights (excluding China) to rivoceranib and has partnered for its development and marketing with HLB-LS in South Korea. Rivoceranib, under the name apatinib, is also approved in China for advanced gastric cancer and in second-line advanced HCC by the Chinese-territory license-holder, Jiangsu Hengrui Pharmaceuticals Company Ltd., (Hengrui Pharma), under the brand name Aitan®. About Elevar Therapeutics Elevar Therapeutics, Inc. is a fully integrated biopharmaceutical company built on the promise of elevating treatment experiences and outcomes for patients who have limited or inadequate therapeutic options. With expertise rooted in oncology, Elevar is focused on identifying and developing promising medicines for complex yet under-treated health conditions across a range of therapeutic areas. Elevar’s lead proprietary drug candidate is rivoceranib. Elevar is headquartered in New Jersey, with offices in South Korea. Additional information is available at ElevarTherapeutics.com. Media Contact: Jeanette Bressi Head, Corporate Communications, Elevar Therapeutics jbressi@elevartherapeutics.com 609-439-3997 Investor Relations Contact: Ashley R. Robinson, LifeSci Advisors, LLC arr@lifesciadvisors.com

Clinical ResultImmunotherapyPhase 3ASCODrug Approval

24 May 2024

·www.fiercepharma.com

Fierce Pharma Asia—AstraZeneca eyes China's innovation, plots Singapore ADC plant; FDA rejects Hengrui's PD-1 drug

AstraZeneca made multiple headlines related to Asia this week. In addition, the FDA's rejection of Hengrui's PD-1 inhibitor made our news roundup. AstraZeneca's CEO wants to tap into China's innovation explosion. The company inked an oncology antibody deal with Harbour BioMed, and it plans to build a $1.5 billion ADC plant in Singapore. Hengrui and Elevar's proposed PD-1/VEGFR liver cancer combination has been rejected by the FDA. Plus more. 1. AstraZeneca to harness China's explosion of innovation to boost cell therapy R&D Innovation in China has “exploded,” and AstraZeneca plans to utilize its growing presence in the country to boost its R&D ambitions in cell therapy, CEO Pascal Soriot said during an investor event. Clinical development of cell therapy in China can “move much faster than anywhere else in the world,” he said. The British pharma has made several deals with Chinese companies over the past two years, including its $1 billion acquisition of Gracell Biotechnologies. 2. AstraZeneca pays $19M to Harbour BioMed's Nona for preclinical cancer antibodies Speaking of tapping into China’s innovation, AstraZeneca paid Harbour BioMed’s U.S. subsidiary Nona Biosceicnes $19 million upfront for preclinical monoclonal antibodies as potential targeted cancer therapies. Nona’s mice-based technology can produce heavy chain-only antibodies. The deal also includes $10 million in near-term payments and another $575 million in biobucks. 3. AstraZeneca places $1.5B bet on end-to-end ADC manufacturing in Singapore Meanwhile, AZ has unveiled plans to build a $1.5 billion antibody-drug conjugate manufacturing facility in Singapore. The site, expected to be operational by 2029, will become the company’s first end-to-end ADC production site. The move comes shortly after CEO Soriot said AZ is building separate drug supply chains for China and Western countries amid geopolitical risks. In recent years, Singapore has become a hot destination for biopharma manufacturing expansions. 4. FDA snubs another China-made PD-1 with rejection of Elevar, Hengrui's liver cancer combo The FDA has rejected Jiangsu Hengrui Pharma and Elevar Therapeutics’ respective applications for PD-1 inhibitor camrelizumab and the VEGFR inhibitor rivoceranib for use as a combination in first-line liver cancer. The FDA cited unresolved issues from the inspection of Hengrui’s manufacturing facility for camrelizumab as well as unfinished clinical trial site inspections. The partners aim to refile as soon as possible. 5. Takeda gets crafty with $1.2B biobucks deal to create molecular glues with Degron Takeda has signed a $1.2 billion biobucks deal with Shanghai’s Degron Therapeutics to work on molecular glue degraders for multiple targets in oncology, neuroscience and inflammation. Degron will use its GlueXplorer platform to find the new glues for therapeutic targets selected by Takeda. Degron has an in-house pipeline, including five early-stage molecular glue candidates in oncology. 6. Otsuka pulls plug on Alzheimer's agitation drug after 2nd failed trial Otsuka has officially ended development of AVP-786 after the NMDA receptor antagonist failed to move the needle in agitation associated with Alzheimer’s disease in a phase 3 trial. Otsuka obtained the drug from its $3.5 billion acquisition of Avanir Pharmaceuticals in 2015, which also gave the Japanese pharma Nuedexta for the rare disorder pseudobulbar affect. 7. Merck KGaA unit avoids DOJ prosecution after exposing scheme to divert drugs to China Two Florida residents pleaded guilty to conspiring to “fraudulently procure deeply discounted products” from Merck’s KGaA’s Sigma-Aldrich and ship them to China using faked export documents. The Department of Justice decided not to prosecute the German firm’s life science division, MilliporeSigma, because the company quickly disclosed the scheme and cooperated with the government’s investigation. 8. Chinese CDMO Asymchem expands footprint with deal to take over former Pfizer UK site China’s Asymchem Laboratories inked a deal to purchase a former Pfizer small molecule API pilot plant and part of its development labs in Sandwich, England. As part of a bigger cost-cutting scheme, Pfizer last year laid off 500 staffers at the plant. The purchase marks Asymchem’s first foray into Europe, and the firm expects to hire 100 workers by the end of the year, including many former Pfizer employees. Other News of Note: 9. Bristol Myers lines up Opdivo treatment in Pakistan, Rwanda and beyond as part of 10-year access campaign 10. Astellas, Yaskawa Electric Corporation ink pact to explore automated cell therapy production 11. Serum Institute deploys first doses of Oxford, Novavax-partnered malaria shot to Africa 12. No treachery here: Celltrion signs 'The Traitors' star Mollie Pearce for bowel disease campaign

AcquisitionPhase 3Cell TherapyLicense out/inADC

17 May 2024

·www.fiercepharma.com

FDA snubs another China-made PD-1 with rejection of Elevar, Hengrui's liver cancer combo

Unresolved manufacturing shortfalls and unfinished inspections of clinical trial sites in Russia and Ukraine led to an FDA complete response letter for Jiangsu Hengrui Pharma and Elevar Therapeutics’ liver cancer drug applications. China-made PD-1 inhibitors just can’t get a clean pass through the FDA. After snubs or delays for three other China-made PD-1 drugs, Jiangsu Hengrui Pharma and Elevar Therapeutics’ respective applications for PD-1 inhibitor camrelizumab and the VEGFR inhibitor rivoceranib have been rejected by the FDA. The pair was hoping for a combination approval in first-line liver cancer. The rejection was first revealed by Elevar’s South Korean parent, HLB, according to the Korea Biomedical Review. Hengrui also disclosed (Chinese, PDF) its complete response letter to the Shanghai Stock Exchange. The pair’s setback is good news for Roche and its anti-PD-L1/VEGF pairing of Tecentriq and Avastin, which is the first FDA-approved immunotherapy-based treatment in first-line liver cancer. For Hengrui and Elevar, the FDA didn’t seem to take issue with their clinical data. Instead, the problems are related to the FDA’s inspections of manufacturing and clinical trial sites. For one, Hengrui has yet to resolve manufacturing deficiencies the FDA spotted during an inspection for camrelizumab, which has been approved in China under the brand name AiRuiKa for various indications. In its CRL, the FDA said it will perform a full evaluation based on Hengrui’s responses to the manufacturing shortfalls, according to the Chinese pharma company. In addition, the FDA has not been able to finish all clinical trial site inspections because of travel restrictions in certain countries, Hengrui said. HLB Chairman Jin Yang-gon, in a YouTube announcement (Korean), disclosed that sites in Russia and Ukraine have yet to be inspected, according to KBR. Jin hopes the regulatory holdup could be resolved through alternative approaches, KBR reports. Hengrui said it plans to keep close communications with the FDA and hopes to refile as soon as possible. The CRL came as a surprise to Elevar because the company has been in label discussions with the FDA as recently as the past week, the company’s CEO Saeho Chong said in a statement to Fierce Pharma. Chong confirmed that the FDA did not raise questions about the clinical data. Manufacturing and clinical site inspection have previously caused trouble for two other China-made PD-1 meds. Before securing the FDA’s go-ahead in October, Coherus BioSciences’ Loqtorzi in 2022 received a CRL because of a quality process change required by the FDA. The company then had to wait for its partner Junshi Biosciences to solve problems the FDA found at its manufacturing facility before facing a Form 483 at a clinical trial site. At BeiGene, COVID-related travel restrictions forced the company to wait an extra 20 months before the FDA could complete its preapproval inspections and approve its PD-1 drug Tevimbra in March. Last week, BeiGene telegraphed a possible delay for its application to expand Tevimbra into first-line esophageal squamous cell carcinoma, because the FDA could be late in scheduling clinical site inspections. An FDA nod could have made camrelizumab the third China-made anti-PD-1 antibody to make it to the U.S. In early 2023, Chinese regulators waved through the camrelizumab-rivoceranib combo as a first-line liver cancer therapy. In addition, camrelizumab, sold under the brand name AiRuiKa in China, is cleared in the country as a monotherapy in second-line liver cancer. Rivoceranib, also known as apatinib and branded as Aitan, has its own single-agent nod in China as a second-line treatment. Camrelizumab and rivoceranib proved their clinical worth in the global phase 3 CARES-310 study. In the trial, the combo showed it could reduce the risk of disease progression or death in first-line liver cancer patients by 48% compared with Bayer’s Nexavar. At the trial’s interim analysis for overall survival, the novel combo also delivered a statistically significant improvement, reducing the risk of death by 38%. When the results were published in The Lancet last year, investigators noted that the combo’s 22.1-month median result for overall survival represented the longest observed figure for any treatment in a global phase 3 trial in the setting. By comparison, in the IMbrave150 trial, Tecentriq and Avastin slashed the risk of death by 42% versus Nexavar at the time of the primary analysis. In a later update, the Roche regimen’s median overall survival was found to be 19.2 months. The two studies’ results can’t be compared directly side by side because of subtle differences in patient characteristics. For example, only 17.3% of patients in CARES-301 were non-Asian, whereas about 40% of patients in IMbrave150 were Asian, excluding those in Japan. Importantly, CARES-301 is a global study with sites in the U.S. Back in 2022, the FDA rejected Innovent Biologics’ PD-1 inhibitor Tyvyt, which was then part of a partnership Eli Lilly, because it only had pivotal data from China. Besides Roche, the Elevar-Hengrui combo, if approved, could compete with AstraZeneca’s dual immunotherapy regimen of Imfinzi and Imjudo. In a phase 3 trial, the AZ regimen cut the risk of death by 22% over Nexavar. In addition, Bristol Myers Squibb recently said its own immunotherapy doublet of Opdivo and Yervoy beat either Nexavar or Eisai’s Lenvima in first-line liver cancer. Rivoceranib was originally developed by Advenchen Laboratories in Southern California and was licensed to Hengrui in China in 2005 and to Elevar—then as LSK BioPharma—for the rest of the world in 2008. As for camrelizumab, Hengrui last year out-licensed the drug’s rights in unresectable liver cancer outside China and Korea to Elevar. HLB acquired Elevar in 2019 through a triangular merger involving the South Korea firm’s U.S. subsidiary. Editor's Note: The story has been updated with additional comments from Elevar.

Clinical ResultAcquisitionPhase 3Drug ApprovalImmunotherapy

100 Deals associated with Apatinib Mesylate

External Link

KEGG	Wiki	ATC	Drug Bank
-	Apatinib Mesylate	L01XE	DB14765

R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Hepatocellular Carcinoma	CN	Jiangsu Hengrui Pharmaceuticals Co., Ltd.	07 Jan 2021
Stomach Cancer	CN	Jiangsu Hengrui Pharmaceuticals Co., Ltd.	17 Oct 2014

Developing

10 top R&D records.

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Germline BRCA-mutated, HER2-negative metastatic breast cancer	NDA/BLA	CN	Jiangsu Hengrui Pharmaceuticals Co., Ltd.	23 Apr 2024
Unresectable Hepatocellular Carcinoma	NDA/BLA	US	Elevar Therapeutics, Inc.	17 May 2023
Advanced Lung Non-Small Cell Carcinoma	Phase 3	CN	Jiangsu Hengrui Pharmaceuticals Co., Ltd.	16 Sep 2020
Advanced Triple-Negative Breast Carcinoma	Phase 3	CN	Jiangsu Hengrui Pharmaceuticals Co., Ltd.	06 Jul 2020
PD-L1 positive Non-Small Cell Lung Cancer	Phase 3	-	Jiangsu Hengrui Pharmaceuticals Co., Ltd.	15 Jun 2020
Platinum-Resistant Ovarian Carcinoma	Phase 3	CN	Jiangsu Hengrui Pharmaceuticals Co., Ltd.	16 Aug 2019
Recurrent ovarian cancer	Phase 3	CN	Jiangsu Hengrui Pharmaceuticals Co., Ltd.	14 Aug 2019
Malignant neoplasm of gastro-oesophageal junction	Phase 3	CN	Jiangsu Hengrui Pharmaceuticals Co., Ltd.	07 Mar 2019
Metastatic Gastroesophageal Junction Adenocarcinoma	Phase 3	CN	Jiangsu Hengrui Pharmaceuticals Co., Ltd.	07 Mar 2019
Small cell lung cancer recurrent	Phase 3	-	Jiangsu Hengrui Pharmaceuticals Co., Ltd.	08 Sep 2018

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT04318730 (ASCO2024) Manual	Phase 2	Adrenocortical Carcinoma Second line	21	Camrelizumab +apatinib	ohneiyarjj(fnvqnrkstm) = emmpkzadte grkazybhym (qkvianpzop, 30-74) View more	Positive	24 May 2024
NCT04814329 (ASCO2024)	Not Applicable	Recurrent Glioblastoma	22	Apatinib in combination with temozolomide	eyjcunysdo(jbffdeojkw) = hthuqthkvc pdhoowjfnn (mlfwolzwyy )	Positive	24 May 2024
				Standard radiotherapy combined with temozolomide	eyjcunysdo(jbffdeojkw) = babxdbrfrd pdhoowjfnn (mlfwolzwyy )
NCT05019690 (ASCO2024)	Phase 2	Triple Negative Breast Cancer Second line	20	Apatinib 250mg	tkvdiakmgc(nuxjkbmdsf) = zjctxoifau pwikwddjja (utrvfaapox, 6.0 - NR) View more	Positive	24 May 2024
NCT05277480 (OAIE/PKUPH-sarcoma 11, ASCO2024)	Phase 3	Osteosarcoma	81	Apatinib plus IE	fvbmuobbnh(uyforllrua) = cbljqyqxqy qexhwstqwm (zfwouirytr, 3.9 - 6.7) View more	Positive	24 May 2024
				IE alone	fvbmuobbnh(uyforllrua) = ztrnertfnp qexhwstqwm (zfwouirytr, 1.4 - 4.6) View more
ChiCTR1900024095 (ASCO2024)	Phase 2	Advanced Pancreatic Adenocarcinoma	30	Camrelizumab+apatinib	jnkrxkyzmf(xixromrsbr) = vgkvloxqdw ccwctnibnw (nooxelqhwm ) View more	Positive	24 May 2024
				Camrelizumab+capecitabine	jnkrxkyzmf(xixromrsbr) = zgiemhfqjp ccwctnibnw (nooxelqhwm ) View more
NCT04296370 (FZPL-Ⅲ-303, ESMO_Virtual2024) Manual	Phase 3	HER2-negative breast cancer Third line \| Second line HER2 Negative \| BRCA2 Mutation (Germline) \| BRCA1 Mutation (Germline)	203	Fuzuloparib + Apatinib	eubqrfochu(kluvasmfwh) = vqfbbporre wkekvhriiu (zweagajfem, 8.4-13.1) View more	Positive	09 May 2024
				Fuzuloparib	eubqrfochu(kluvasmfwh) = bldlcbzeim wkekvhriiu (zweagajfem, 4.2-7.6) View more
ChiCTR2000034109 (SPACE, Literature) Manual	Phase 1	Advanced gastric carcinoma First line	34	Camrelizumab+apatinib+chemotherapy	trpkbrpnnw(dmrhdruszd) = not identified xvwhivsfxu (opubxbbpcm ) View more	Positive	25 Mar 2024
ChiCTR2300076887 (ESMO_SRC2024) Manual	Not Applicable	Neuroendocrine Tumors First line	12	Camrelizumab + apatinib mesylate	xingnvjhuu(yuzggzxrwc) = ybjcdlxfsx bhwwjsbdaz (tdwssikkpp ) View more	Positive	15 Mar 2024
NCT04190745 (Pubmed)	Phase 2	Advanced gastric carcinoma Second line	-	Apatinib plus Toripalimab	dizvszsudk(clxxkkthrh) = asbqzhzzta pqvtfdmnta (qjnzmfnctl ) View more	Negative	16 Feb 2024
				Physician's choice of chemotherapy	dizvszsudk(clxxkkthrh) = kkjmgkwjem pqvtfdmnta (qjnzmfnctl ) View more
NCT03764293 (CTgov)	Phase 3	Hepatocellular Carcinoma	543	Rivoceranib+Camrelizumab (Camrelizumab+Rivoceranib Arm)	nwkovqqpnp(ljgofcgcst) = qjwunbkqcw mkuecuvdak (qqwujcnprp, xqidmledef - raxqmhhoqd) View more	-	06 Feb 2024
				Sorafenib (Sorafenib Arm)	nwkovqqpnp(ljgofcgcst) = imgqatvhns mkuecuvdak (qqwujcnprp, ieymyvyujk - arpmvdovge) View more

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