On June 27, 2021 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 reported that the National Medical Products Administration (NMPA) of China has approved the supplemental New Drug Application (sNDA) for TYVYT (sintilimab injection) in combination with BYVASDA (bevacizumab biosimilar injection) as a first-line treatment for people with advanced or unresectable hepatocellular carcinoma (HCC). This is the first regulatory approval of a PD-1 inhibitor-based combination therapy for the first-line treatment for HCC.

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This is also the fourth NMPA-approved indication of TYVYT (sintilimab injection) as well as the fourth NMPA-approved indication of BYVASDA (bevacizumab biosimilar injection). TYVYT (sintilimab injection) was approved in China for the treatment of relapsed or refractory classical Hodgkin’s lymphoma in December 2018, the first-line treatment of nonsquamous non-small cell lung cancer (NSCLC) in February 2021, and the first-line treatment of squamous NSCLC in June 2021. BYVASDA (bevacizumab biosimilar injection) was previously approved for advanced non-small cell lung cancer, metastatic colorectal cancer, and adult recurrent glioblastoma.

This new approval was based on the results of a randomized, open-label Phase 3 clinical trial (ORIENT-32) of TYVYT (sintilimab injection) in combination with BYVASDA (bevacizumab biosimilar injection) as first-line therapy for unresectable HCC. Based on the interim analysis conducted by the Independent Data Monitoring Committee (IDMC), TYVYT (sintilimab injection) in combination with BYVASDA (bevacizumab biosimilar injection) demonstrated a statistically significant improvement in overall survival (OS) and progression-free survival (PFS) as assessed by Independent Radiographic Review Committee (IRRC) compared to sorafenib, meeting the pre-defined efficacy criteria. Safety analyses revealed no new safety signals. The ORIENT-32 results were published in The Lancet Oncology on June 15, 2021.

Professor Fan Jia from Zhongshan Hospital of Fudan University stated," In China, liver cancer is the second most common cause of cancer-related death and ranks fourth in terms of incidence with a five-year survival rate of only 10 percent. Response of hepatocellular carcinoma to chemotherapy and targeted therapy is undesirable, while immunotherapy has emerged as breakthrough treatment for hepatocellular carcinoma. The ORIENT-32 has demonstrated that sintilimab plus bevacizumab can extend the overall survival and progression-free survival in this patient population and bring significant clinical benefits. The approval will provide a new option for the first-line treatment of these patients with few systemic options, and also contribute to the ‘Healthy China 2030’."

Dr. Yongjun Liu, President of Innovent, stated: "Liver cancer is the third leading cause of cancer death globally, and China accounts for over 50 percent of all new cases and deaths worldwide. The disease is a serious threat to the life and health of Chinese people and a heavy burden on society and families, with hepatocellular carcinoma accounting for 85 to 90 percent of all liver cancer. We are very pleased that TYVYT (sintilimab injection) plus BYVASDA (bevacizumab biosimilar injection) – two drugs recognized by the China national innovation drug development project – is the first approved PD-1 inhibitor-based combination therapy for the first-line treatment of people with hepatocellular carcinoma. Innovent is proud to continue delivering on our mission of developing high-quality biopharmaceuticals that are affordable to ordinary people, while also contributing to the ‘Healthy China 2030’ Plan for cancer prevention and treatment."

About the ORIENT-32 Trial
ORIENT-32 is a Phase 3 randomized, open-label, multi-center study conducted in China to evaluate the efficacy and safety of TYVYT (sintilimab injection) in combination with BYVASDA (bevacizumab biosimilar injection) compared to sorafenib for the first-line treatment of patients with advanced hepatocellular carcinoma（ClinicalTrials.gov, NCT03794440）. The primary endpoints of the trial were overall survival (OS) and progression-free survival (PFS) as assessed by Independent Radiographic Review Committee (IRRC) based on RECIST v1.1.

A total of 571 patients were enrolled and randomly assigned 2:1 to receive either TYVYT (sintilimab injection) plus BYVASDA (bevacizumab biosimilar injection) or sorafenib until disease progression or unacceptable toxicity. The combination therapy showed significant improvements in OS and PFS compared to sorafenib, and safety was consistent with previously reported safety profiles of each drug. The full results of ORIENT-32 were published in The Lancet Oncology on June 15, 2021.

About Hepatocellular Carcinoma
Primary liver cancer（PLC）is a common malignancy of the digestive system worldwide, among which about half of all new cases and deaths occur in China. The main pathological types of liver cancer are hepatocellular carcinoma (HCC), which accounts for 85 to 90 percent, and a small number of cases of intrahepatic cholangiocarcinoma（ICC）and HCC-ICC mixed liver cancer. In China, HCC is primarily caused by hepatitis B virus (HBV) and/or hepatitis C virus (HCV) infection.

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 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 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 nonsquamous 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 hepatocellular carcinoma
Additionally, Innovent currently has a regulatory submission under review in China for sintilimab for the second-line treatment of squamous non-small cell lung cancer.

Innovent also has two clinical studies of sintilimab that have met their primary endpoints:

In combination with cisplatin plus paclitaxel or cisplatin plus 5-fluorouracil for the first-line treatment of esophageal squamous cell carcinoma
The second-line treatment of esophageal squamous cell carcinoma
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 nonsquamous non-small cell lung cancer.

Sintilimab was included in China’s National Reimbursement Drug List (NRDL) in 2019 as the first PD-1 inhibitor and the only PD-1 included in the list in that year.

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. (Press release, Innovent Biologics, JUN 27, 2021, View Source [SID1234584387])

On June 27, 2021 Tvardi Therapeutics, a Houston biopharmaceutical company, reported that it had raised $74 million in a new round of financing that will send its drug candidates through mid-stage clinical trials for treatment of cancer and fibrosis (Press release, Tvardi Therapeutics, JUN 27, 2021, View Source [SID1234584511]). The company, founded in 2017, specializes in the development of STAT3 inhibitors, which induce death in cancer cells. Tvardi CEO Imran Alibhai said the latest round of funding will help the company move out of "stealth mode" and raise its public profile.

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"With this financing we are positioned to advance the clinical development" of the company’s drug candidates, Alibhai said. The money will also help the company to expand its workforce, he added. The company’s latest round of financing is known as Series B. Series B is the third round of fundraising for new companies that typically comes after the startups have met certain milestones in their growth.

Officials with the company say the key molecule used in its drugs, TTI-101, has been shown in early clinical studies to be well tolerated among patients and can shrink a broad range of tumors.

On June 25, 2021 MorphoSys AG (FSE: MOR; NASDAQ: MOR) and Incyte (NASDAQ: INCY) reported that the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has issued a positive opinion recommending the conditional marketing authorization of tafasitamab in combination with lenalidomide, followed by tafasitamab monotherapy, for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) who are not eligible for autologous stem cell transplantation (ASCT) (Press release, MorphoSys, JUN 25, 2021, View Source [SID1234584363]).

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"The CHMP’s positive opinion of tafasitamab is a pivotal step towards addressing an urgent unmet medical need for the 30-40% of patients with relapsed or refractory DLBCL who do not respond to initial therapy or relapse thereafter," said Steven Stein, M.D., Chief Medical Officer, Incyte. "Following the U.S. FDA’s approval of tafasitamab in July 2020, we eagerly await the European Commission’s decision as we look forward to bringing this new therapy to eligible patients in Europe as soon as possible."

"Tafasitamab in combination with lenalidomide represents an important new targeted treatment option for patients with relapsed or refractory DLBCL," said Dr. Malte Peters, Chief Research & Development Officer, MorphoSys. "Patients with relapsed or refractory DLBCL have limited treatment options and often face a poor prognosis. There is an urgent need for effective therapies and if approved, this combination could provide patients in Europe with an important new therapeutic option."

The CHMP opinion to recommend the use of tafasitamab is now being reviewed by the European Commission, which has the authority to grant marketing authorization for medicinal products in the European Union (EU). If approved, tafasitamab would be commercialized in the EU under the brand name Minjuvi.

DLBCL is the most common type of non-Hodgkin lymphoma in adults worldwide comprising 40% of all cases1 and characterized by rapidly growing masses of malignant B-cells in the lymph nodes, spleen, liver, bone marrow or other organs.2 It is an aggressive disease with about one in three patients not responding to initial therapy or relapsing thereafter.3 In Europe, each year approximately 16,000 patients are diagnosed with relapsed or refractory DLBCL.4,5,6

MorphoSys and Incyte share global development rights to tafasitamab and Incyte has exclusive commercialization rights to tafasitamab outside the United States. MorphoSys and Incyte co-commercialize tafasitamab under the brand name Monjuvi in the United States.

About L-MIND

The L-MIND trial is a single arm, open-label Phase 2 study (NCT02399085) investigating the combination of tafasitamab and lenalidomide in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) who have had at least one, but no more than three prior lines of therapy, including an anti-CD20 targeting therapy (e.g., rituximab), who are not eligible for high-dose chemotherapy (HCD) or autologous stem cell transplant (ASCT). The study’s primary endpoint is overall response rate (ORR). Secondary outcome measures include duration of response (DoR), progression-free survival (PFS) and overall survival (OS). The study reached its primary completion in May 2019.

For more information about L-MIND, visit View Source

About Tafasitamab

Tafasitamab is a humanized Fc-modified cytolytic CD19 targeting monoclonal antibody. In 2010, MorphoSys licensed exclusive worldwide rights to develop and commercialize tafasitamab from Xencor, Inc. Tafasitamab incorporates an XmAb engineered Fc domain, which mediates B-cell lysis through apoptosis and immune effector mechanism including Antibody-Dependent Cell-Mediated Cytotoxicity (ADCC) and Antibody-Dependent Cellular Phagocytosis (ADCP).

Monjuvi (tafasitamab-cxix) is approved by the U.S. Food and Drug Administration in combination with lenalidomide for the treatment of adult patients with relapsed or refractory DLBCL not otherwise specified, including DLBCL arising from low grade lymphoma, and who are not eligible for autologous stem cell transplant (ASCT). This indication is approved under accelerated approval based on overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).

Tafasitamab is being clinically investigated as a therapeutic option in B-cell malignancies in several ongoing combination trials.

Minjuvi and Monjuvi are registered trademarks of MorphoSys AG. Tafasitamab is marketed under the brand name Monjuvi in the US. If approved in the EU, tafasitamab will be marketed under the brand name Minjuvi.

XmAb is a registered trademark of Xencor, Inc.

On June 25, 2021 Sandoz reported the launch of generic oncology treatment Pemetrexed in 11 countries across Europe, including Germany, Switzerland, Netherlands, and Spain (Press release, Novartis, JUN 25, 2021, View Source [SID1234584364]).

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Pemetrexed, as a monotherapy or in combination with cisplatin, is indicated for first-line, second-line and maintenance treatment of patients with locally advanced or metastatic Non-Small Cell Lung Cancer (NSCLC) other than predominantly squamous cell histology, and for the treatment of chemotherapy naïve patients with unresectable malignant pleural mesothelioma.3

Globally, 1.8 million people died from lung cancer in 2020 including over 26,000 deaths from mesothelioma, and approximately 2.2 million new cases of lung cancer including 31,000 new cases of mesothelioma were diagnosed.4 NSCLC is the most prevalent form of the disease, affecting approximately 85% of those diagnosed with lung cancer.5,6

"At Sandoz, we are committed to using our expertise in product development to enable us to deliver high quality, innovative products that address the needs of patients and healthcare professionals," said Rebecca Guntern, Head of Sandoz Region Europe. "By providing Pemetrexed in a ready-to-dilute format and in an additional, higher-strength dosage, we believe that this treatment option will not only be more cost-effective for payers, but patients and physicians will also be able to benefit from the reduced preparation steps required."

Pemetrexed is a multi-targeted antifolate anti-cancer agent that disrupts crucial folate-dependent metabolic processes essential for cell replication. It inhibits folate-dependent enzymes critical to the de-novo biosynthesis of nucleotides leading to the disruption of DNA replication. Patients receive the treatment via a 10-minute intravenous infusion in a hospital setting.3

Further launches across Europe are expected throughout the second half of 2021.

On June 25, 2021 Sanofi and Regeneron reported that The European Commission (EC) has approved its PD-1 inhibitor Libtayo (cemiplimab) for the first-line treatment of adults with non-small cell lung cancer (NSCLC) whose tumor cells have ≥50% PD-L1 expression and no EGFR, ALK or ROS1 aberrations (Press release, Sanofi, JUN 25, 2021, View Source [SID1234584365]). Patients must have metastatic NSCLC or locally advanced NSCLC and not be a candidate for definitive chemoradiation.

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Libtayo is now approved for three advanced cancers in the European Union. The EC also approved Libtayo in advanced basal cell carcinoma, the first treatment to be indicated for those patients who have progressed on or are intolerant to a hedgehog pathway inhibitor (HHI). In 2019, Libtayo was approved by the EC as the first treatment for adults with metastatic or locally advanced cutaneous squamous cell carcinoma (CSCC) who are not candidates for curative surgery or curative radiation. Across all of its approved indications, Libtayo had a generally consistent safety profile. Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue during or after treatment with Libtayo.

"We are confident that Libtayo has the potential to become an important treatment option for patients in the European Union and thank all the investigators, patients and their families who helped us reach this milestone," said Peter C. Adamson, M.D., Global Development Head, Oncology at Sanofi. "We are anticipating results from our ongoing Phase 3 trial of Libtayo plus chemotherapy in patients with advanced non-small cell lung cancer and remain committed to studying Libtayo in additional cancer settings where there is the potential to improve the outcome for patients."

The EC approval in advanced NSCLC is based on data from a global Phase 3 trial that enrolled 710 patients from 24 countries. The trial, which was one of the largest for a PD-1 inhibitor in advanced NSCLC, was designed to be more reflective of clinical practice by including challenging-to-treat and often underrepresented disease characteristics. Among those enrolled, 12% had pre-treated and clinically stable brain metastases, 44% had squamous cell histology and 16% had locally advanced NSCLC that was not a candidate for definitive chemoradiation. Furthermore, patients whose disease progressed in the trial were able to change their therapy: those assigned to chemotherapy could crossover to Libtayo treatment, while those assigned to Libtayo monotherapy could continue Libtayo treatment and add four cycles of chemotherapy.

In the overall study population, Libtayo significantly reduced the risk of death by 32% and extended median overall survival (OS) by 8 months compared to chemotherapy, even with 74% of patients crossing over to Libtayo following disease progression on chemotherapy (hazard ratio [HR]: 0.68; 95% confidence interval [CI]: 0.53-0.87; p=0.0022). The median OS was 22 months for Libtayo (range: 18 months to not evaluable) and 14 months for chemotherapy (range: 12 to 19 months). A prespecified analysis of data from patients whose cancers had PD-L1 expression ≥50% (n=563) based on a validated assay was also conducted. As published in The Lancet, Libtayo reduced the risk of death by 43% for patients in this population; median OS was not reached for Libtayo (95% CI: 18 months to not evaluable) and was 14 months for chemotherapy (95% CI: 11 to 18 months).

In the Phase 3 trial, safety was assessed in 697 patients, with a duration of exposure of 27 weeks (range: 9 days to 115 weeks) for the Libtayo group and 18 weeks (range: 18 days to 87 weeks) for the chemotherapy group. Serious adverse reactions (AEs) in at least 2% of patients were pneumonia (5% Libtayo, 6% chemotherapy) and pneumonitis (2% Libtayo, 0% chemotherapy). Treatment was permanently discontinued due to AEs in 6% of Libtayo patients; AEs resulting in permanent discontinuation in at least 2 patients were pneumonitis, pneumonia, ischemic stroke and increased aspartate aminotransferase. No new Libtayo safety signals were observed.

"Libtayo has demonstrated a highly significant improvement in overall survival compared to chemotherapy for patients with advanced non-small cell lung cancer with high PD-L1 expression and a variety of challenging-to-treat disease characteristics," said Israel Lowy, M.D., Ph.D., Senior Vice President, Translational and Clinical Sciences, Oncology at Regeneron. "Beyond the primary analysis, we continue to conduct post-hoc analyses of our Phase 3 trial with the goal of informing treatment in this patient population."

About the Phase 3 Trial in Advanced NSCLC

EMPOWER-Lung 1 was an open-label, randomized, multi-center Phase 3 trial designed to investigate Libtayo monotherapy compared to platinum-doublet chemotherapy as first-line treatment in patients with advanced NSCLC who tested positive for PD-L1 in ≥50% of tumor cells and had no EGFR, ALK or ROS1 aberrations. PD-L1 expression was confirmed using the Agilent Dako PD-L1 IHC 22C3 pharmDx kit.

The trial randomized 710 patients 1:1 who had either previously untreated metastatic NSCLC (stage IV) or locally advanced NSCLC (stage IIIB/C) who were not candidates for surgical resection or definitive chemoradiation or who had progressed after treatment with definitive chemoradiation. Those receiving Libtayo were intravenously administered 350 mg dose every three weeks for up to 108 weeks, while those receiving chemotherapy received an investigator-selected, platinum-doublet chemotherapy regimen for four to six cycles (with or without maintenance pemetrexed chemotherapy).

The primary endpoints were OS and progression-free survival, and secondary endpoints included objective response rate, duration of response and quality of life. In 2020, the trial was stopped early due to a significant improvement in OS.

About Libtayo

Libtayo is a fully human monoclonal antibody targeting the immune checkpoint receptor PD-1 on T-cells. By binding to PD-1, Libtayo has been shown to block cancer cells from using the PD-1 pathway to suppress T-cell activation.

The extensive clinical program for Libtayo is focused on difficult-to-treat cancers. Current clinical development programs include Libtayo in combination with chemotherapy for advanced NSCLC irrespective of PD-L1 expression and Libtayo monotherapy for advanced cervical cancer. Libtayo is also being investigated in combination with either conventional or novel therapeutic approaches for other solid tumors and blood cancers. These potential uses are investigational, and their safety and efficacy have not been evaluated by any regulatory authority.

The generic name for Libtayo in its approved U.S. indications is cemiplimab-rwlc, with rwlc as the suffix designated in accordance with Nonproprietary Naming of Biological Products Guidance for Industry issued by the U.S. Food and Drug Administration (FDA). Libtayo is being jointly developed by Regeneron and Sanofi under a global collaboration agreement.