On August 17, 2020 G1 Therapeutics, Inc. (Nasdaq: GTHX), a clinical-stage oncology company, reported that the U.S. Food and Drug Administration (FDA) has accepted the New Drug Application (NDA) for trilaciclib for small cell lung cancer (SCLC) patients being treated with chemotherapy and granted Priority Review with a Prescription Drug User Fee Act (PDUFA) action date of February 15, 2021 (Press release, G1 Therapeutics, AUG 17, 2020, View Source [SID1234563738]). Trilaciclib is a first-in-class investigational therapy designed to preserve bone marrow and immune system function during chemotherapy and improve patient outcomes.

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"There are currently no available therapies to protect patients from chemotherapy-induced toxicities before they occur," said Raj Malik, M.D., Chief Medical Officer and Senior Vice President, R&D. "If approved, trilaciclib would be the first proactively administered myelopreservation therapy that is intended to make chemotherapy safer and reduce the need for rescue interventions, such as growth factor administrations and blood transfusions."

The FDA grants Priority Review to applications for potential therapies that, if approved, would be significant improvements in the safety or effectiveness of the treatment, diagnosis, or prevention of serious conditions when compared to standard applications. The trilaciclib NDA was supported by compelling myelopreservation data from three randomized, double-blind, placebo-controlled clinical trials in which trilaciclib was administered prior to chemotherapy treatment in patients with SCLC. Trilaciclib has been granted Breakthrough Therapy Designation by the FDA. In the NDA acceptance letter, the FDA also stated that it is currently not planning to hold an advisory committee meeting to discuss this application.

"While undergoing chemotherapy, many patients experience significant myelosuppression, become fatigued and susceptible to infection, and often require transfusions and growth factor administrations," said Jared Weiss, M.D., Lineberger Comprehensive Cancer Center, University of North Carolina Chapel Hill, NC. "Preventing bone marrow damage proactively is an opportunity to improve the quality of life of patients receiving chemotherapy for small cell lung cancer and reduce costly rescue interventions."

Myelosuppression is the result of damage to bone marrow stem cells and is one of the most common side effects of chemotherapy. Myelosuppression can lead to serious conditions such as anemia, neutropenia or thrombocytopenia, which have broad ranging clinical, patient experience and economic impacts on ongoing cancer treatment and overall outcomes. In clinical trials, trilaciclib significantly reduced chemotherapy-induced myelosuppression, and patients receiving trilaciclib experienced fewer dose delays/reductions, infections, hospitalizations, and need for rescue therapies compared to patients receiving chemotherapy alone.

Expanded Access Program
G1 is making trilaciclib available to SCLC patients in the U.S., who are unable to enter clinical trials and for whom there are no appropriate alternative treatments while the trilaciclib NDA is under regulatory review, pursuant to FDA’s expanded access program (EAP). To facilitate needed access through the EAP, G1 is collaborating with Bionical Emas, a global specialist clinical research organization (CRO). For more information about the EAP access to trilaciclib, email [email protected].

"Complications from myelosuppression have been a long-standing challenge when treating patients with SCLC," said Dr. Malik. "Establishing an expanded access program provides qualified patients in serious need with access to trilaciclib while the NDA is under review."

Trilaciclib in Small Cell Lung Cancer
Trilaciclib is a first-in-class investigational therapy designed to improve outcomes for people with cancer treated with chemotherapy. In 2019, trilaciclib received FDA Breakthrough Therapy Designation, and, in June 2020, G1 submitted the NDA based on myelopreservation data from three randomized, double-blind, placebo-controlled clinical trials in which trilaciclib was administered prior to chemotherapy in patients with small cell lung cancer (SCLC). In August 2020, G1 received FDA Priority Review with the Prescription Drug User Fee Act (PDUFA) date of February 15, 2021.

In June 2020, G1 announced a co-promotion agreement with Boehringer Ingelheim for trilaciclib in small cell lung cancer in the U.S. and Puerto Rico. If approved, G1 will lead marketing, market access and medical engagement initiatives for trilaciclib. The Boehringer Ingelheim oncology commercial team, well-established in lung cancer, will lead sales force engagement initiatives. G1 will book revenue and retain development and commercialization rights to trilaciclib and pay Boehringer Ingelheim a promotional fee based on net sales. The three-year agreement does not extend to additional indications that G1 is evaluating for trilaciclib. Press release details of the G1/ Boehringer Ingelheim agreement can be found here.

Evaluating Trilaciclib in Other Cancers
In a randomized trial of women with metastatic triple-negative breast cancer, preliminary data showed that trilaciclib improved overall survival when administered in combination with chemotherapy compared with chemotherapy alone. The company plans to present final overall survival data from this trial in the fourth quarter of 2020. Trilaciclib is being evaluated in neoadjuvant breast cancer as part of the I-SPY 2 TRIAL, and the company expects to initiate a Phase 3 trial in patients treated with chemotherapy for colorectal cancer in the fourth quarter of 2020.

On August 17, 2020 DaVita Inc. (NYSE: DVA) ("DaVita"), a health care provider focused on transforming care delivery to improve quality of life for patients globally and one of the largest providers of kidney care services in the United States, reported that it has commenced a modified "Dutch auction" tender offer for shares of its common stock for an aggregate purchase price of up to $1.0 billion at a price per share of not less than $77.00 and not more than $88.00 (Press release, DaVita, AUG 17, 2020, View Source [SID1234563733]). The tender offer will expire at 12:00 midnight, New York City time, at the end of the day on September 14, 2020, unless extended by DaVita or otherwise terminated. Tenders of shares must be made on or prior to the expiration of the tender offer and may be withdrawn at any time prior to the expiration of the tender offer, in each case, in accordance with the procedures described in the tender offer materials.

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A modified "Dutch auction" tender offer allows shareholders to indicate how many shares and at what price within DaVita’s specified range they wish to tender. Based on the number of shares tendered and the prices specified by the tendering shareholders, DaVita will determine the lowest price per share within the specified range that will enable DaVita to purchase shares having an aggregate purchase price of up to $1.0 billion. DaVita also reserves the right, in the event that more than $1.0 billion of its shares are tendered in the tender offer at or below the purchase price, to purchase at its option up to an additional number of outstanding shares of common stock not to exceed 2% of the total number of its shares of common stock (exclusive of any shares of common stock held by or for DaVita’s account or by or for the account of any of DaVita’s subsidiaries) without amending or extending the tender offer. All shares purchased by DaVita in the tender offer will be purchased at the same price. Shareholders whose shares are purchased in the tender offer will be paid the determined purchase price in cash, less any applicable withholding taxes and without interest, promptly after the expiration of the tender offer.

DaVita expects to finance the share purchases in the tender offer with cash on hand, and to the extent necessary, borrowings under its currently undrawn $1.0 billion revolving line of credit under its senior secured credit facilities. The tender offer is not conditioned upon the receipt of financing or any minimum number of shares being tendered, but it is subject to certain other conditions. The tender offer documents contain tendering instructions and a complete explanation of the tender offer’s terms and conditions.

The dealer manager for the tender offer is BofA Securities, Inc. Georgeson LLC is serving as information agent for the tender offer and Computershare Inc. is serving as the depositary for the tender offer.

Neither DaVita, its directors, the dealer manager, the information agent, nor the depositary makes any recommendation as to whether to tender shares or as to the price at which to tender them.

Additional Information Regarding the Planned Tender Offer

On August 17, 2020 CARsgen Therapeutics, a leader in developing novel CAR-T cell therapies against solid tumors, reported its publication of the 7×21 CAR-T technology in CLINICAL CANCER RESEARCH (Press release, Carsgen Therapeutics, AUG 17, 2020, View Source [SID1234563732]). The article is titled "Coexpression of IL-7 and CCL21 increases efficacy of CAR-T cells in solid tumors without requiring preconditioned lymphodepletion."

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Current challenges in CAR-T cell therapy for solid tumor malignancies include T cell survival, T cell infiltration, and antigen heterogeneity. CARsgen recently collaborated with State Key Laboratory of Oncogenes and Related Genes at the Shanghai Cancer Institute to overcome these obstacles. In this study, the CAR-T cells were engineered to co-express the cytokines IL-7 and CCL21 (7×21 CAR-T). Study results indicated the 7×21 CAR-T cells significantly outperformed the conventional CAR-T cells in cell proliferation and chemotaxis. Without the cyclophosphamide (CPA) precondition, the 7×21 CAR-T cells displayed superior therapeutic effects to both the conventional CAR-T cells and the 7×19 CAR-T cells, which co-expressed IL-7 and CCL19, in treating three different solid tumors. The 7×21 CAR-T cells could also efficiently inhibit the tumor growth of xenografts containing CLDN18.2-positive and CLDN18.2-negative tumor cells at a 1:1 ratio, and even resulting in complete tumor remission. The mechanistic study revealed that the 7×21 CAR T-cell treatment not only significantly improved the survival and infiltration of CAR-T cells and dendritic cells in vivo, but also led to less angiogenesis in tumors. These results support that the 7×21 CAR-T technology could be a promising therapeutic approach for the treatment of solid tumors.

The article may be found on following link: View Source

On August 17, 2020 Thermo Fisher Scientific reported that it has signed a companion diagnostic (CDx) agreement with Hengrui Therapeutics, Inc. (HTI), a U.S. subsidiary of Chinese pharmaceutical company Jiangsu Hengrui Medicine Co., Ltd. (JHM), to develop a CDx that will leverage the Oncomine Precision Assay, which runs on the new Ion Torrent Genexus System (Press release, Thermo Fisher Scientific, AUG 17, 2020, View Source [SID1234563731]). Once commercialized, the CDx will be used to identify non-small cell lung cancer (NSCLC) patients who may be eligible for pyrotinib, JHM’s novel, irreversible pan-HER2 tyrosine kinase inhibitor.

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HER2 mutations are present in about 4 percent of patients with NSCLC, yet there is currently no targeted therapy approved by the U.S. Food & Drug Administration (FDA) for patients with HER2-mutated NSCLC.1 HTI recently released results from a phase 2 clinical trial demonstrating that pyrotinib showed promising antitumor activity in patients with HER2-mutant advanced NSCLC who were previously treated with chemotherapy. The drug received conditional approval in China for the treatment of HER2-positive, advanced or metastatic breast cancer in chemotherapy-treated patients in 2018 based on positive phase 2 clinical trial results and full approval in 2020 based on two successful phase 3 studies. HTI’s global clinical trial program for pyrotinib is currently in phase 3 clinical trials, with studies underway in China, Europe and the United States.

"An approved targeted therapy for patients with HER2-mutated non-small cell lung cancer could save thousands of lives," said Dr. Lianshan Zhang, R&D president of JHM. "We are excited to partner with Thermo Fisher on a companion diagnostic that will make it easier for clinicians to identify patients who may benefit from pyrotinib, helping us broaden participation in clinical trials and make precision medicine available for more patients."

Under the terms of the agreement, Thermo Fisher will retain rights to commercialize the test globally and will seek approval from regulatory agencies. The company has previously announced a CDx agreement that also leverages the Oncomine Precision Assay for the Genexus System. In June the FDA granted the assay Breakthrough Device Designation to identify isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) mutations in low-grade glioma patients.

"We are seeing strong demand from our pharmaceutical partners for our NGS solutions," said Garret Hampton, president of clinical next-generation sequencing and oncology at Thermo Fisher Scientific. "The Oncomine Precision Assay for the Genexus System is designed to comply with evolving regulations, such as those currently in development in China and Europe. It can be deployed to prospectively test and enroll clinical trial participants as well as for retrospective analysis of local laboratory tests used for clinical trial enrollment. It is the ideal solution to support trial programs on a global scale."

The Oncomine Precision Assay can detect more than 50 cancer-related biomarkers from formalin-fixed paraffin-embedded (FFPE) tumor tissues or liquid biopsy specimens. It is designed to run on the Genexus System, a first-of-its-kind NGS platform that features an automated workflow with a one-day turnaround time and the lowest sample requirements on the market for detection of both DNA and RNA variants. Currently, the integrated sequencer and assay are labeled for research use only.

On August 17, 2020 Shanghai Henlius Biotech, Inc. (2696.HK) reported on August 14 that the trastuzumab biosimilar HLX02, developed and manufactured by Henlius independently, has been approved by the National Medical Products Administration (NMPA) (Press release, Shanghai Henlius Biotech, AUG 17, 2020, View Source [SID1234563730]). On 27th July, HLX02 (EU brand name Zercepac) has also been approved by the European Commission (EC), making HLX02 the first China-developed mAb biosimilar to be approved both in China and in the EU. The common name of HLX02 is trastuzumab injection (150mg/vial, without preservative) and it is indicated for the treatment of HER2-positive early breast cancer, HER2-positive metastatic breast cancer and HER2-positive metastatic gastric cancer. Trastuzumab has been included in China’s National Reimbursement Drug List (NRDL) in 2017. According to the "Interim Measures for the Administration of Drugs in the NRDL", drugs in the NRDL are managed by their common names, and drugs with common names that have been listed in the NRDL will automatically enter the NRDL.

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During the development process of HLX02, Henlius strictly followed the NMPA and European Medicines Agency (EMA) biosimilar guidelines and has taken multiple head-to-head comparisons between HLX02 and the reference trastuzumab. Results from analytical studies, preclinical studies, a Phase 1 clinical study and a global multi-centre Phase 3 clinical study showed that HLX02 is highly similar to the reference trastuzumab in terms of quality, safety and efficacy. Henlius has implemented the concept of QbD (quality by design) in process development for HLX02 and has adopted single-use technology for its manufacturing, leading to decreased risk of contamination and increased production efficiency. Manufacturing site of HLX02 and its quality management system have passed multiple on-site inspections and audits by NMPA, EMA, EU Qualified Persons (QP) and international business partners of Henlius, and have obtained China and EU GMP certificates. To accelerate the commercialisation of HLX02, Henlius has built a professional and efficient international commercial team and established an innovative commercial model.

Dr. Scott Liu, co-founder and CEO of Henlius, said, "As the leading company in the biologics industry of China, Henlius’ self-developed rituximab biosimilar HLX01 was approved by the NMPA in 2019, making it the first biosimilar in China. Now we are proud that HLX02 can benefit Chinese patients. The recognition of HLX02 by domestic and international regulatory authorities is the results of insisting the quality standards of Henlius, and Henlius will continue making efforts in providing affordable and effective therapies for patients worldwide."

Mr. Wenjie Zhang, President of Henlius, said, "HLX02 is the second product successfully approved for launch of Henlius and the first product that has received recognition from international drug regulatory agency. We are very grateful to all the physicians, nurses, patients and regulatory authorities that have contributed to or supported the studies of HLX02. We hope that HLX02 will benefit HER2-positive breast cancer and gastric cancer patients both in urban and rural areas in China."