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Marketing authorization granted for darolutamide in Japan

On January 23, 2020 Orion Corporation reported the Japanese Ministry of Health, Labor and Welfare (MHLW) has granted marketing authorization for darolutamide, under the brand name Nubeqa, for the treatment of men with non-metastatic castration-resistant prostate cancer (nmCRPC) (Press release, Orion , JAN 23, 2020, View Source [SID1234553465]).

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The approval is based on the Phase III ARAMIS trial evaluating the efficacy and safety of darolutamide plus androgen deprivation therapy (ADT) compared to placebo plus ADT, showing a highly significant improvement in the primary efficacy endpoint of metastasis-free survival (MFS), with a median 40.4 months for darolutamide plus ADT versus 18.4 months for placebo plus ADT (HR=0.41, 95% CI 0.34-0.50; P<0.001). The androgen receptor inhibitor (ARi), which is jointly developed by Orion and Bayer is already approved in the U.S. and Brazil and filings in the European Union and other regions are underway or planned by Bayer.

"Patients with nmCRPC are usually asymptomatic, but have a rising blood prostate specific antigen (PSA) despite ADT treatment, and it is important to prevent their cancer from becoming metastatic and symptomatic. The overarching goals of treatment in this setting are to delay the spread of prostate cancer and limit the burdensome side effects of therapy. Darolutamide provides nmCRPC patients now also in Japan a new therapeutic option that addresses these questions" said Christer Nordstedt, Senior Vice President, Research and Development, Orion Corporation.

In Japan, over 89,000 men are estimated to be diagnosed with prostate cancer annually, making it the second most-common cancer diagnosis in Japanese men after stomach cancer. Prostate cancer that is treated with ADT but keeps progressing even when the amount of testosterone is reduced to very low levels in the body is known as castration-resistant prostate cancer (CRPC).1 In men with progressive nmCRPC, a rapid prostate specific antigen (PSA) doubling time has been consistently associated with reduced time to first metastasis and death.1

In the ARAMIS trial, overall survival (OS) and time to pain progression were additional secondary efficacy endpoints. At the time of final MFS analysis, a positive trend in OS was observed; OS data were not yet mature. The MFS result was additionally supported by a delay in time to pain progression as compared to placebo plus ADT. All other secondary endpoints, time to cytotoxic chemotherapy, and time to a symptomatic skeletal event (SSE), demonstrated a benefit in favor of darolutamide.

Adverse reactions occurring more frequently in the darolutamide plus ADT arm (≥2% absolute increase in frequency compared to placebo plus ADT) were fatigue (16% vs. 11%), pain in extremity (6% vs. 3%), and rash (3% vs. 1%). Discontinuation due to adverse events occurred in 9% of patients in both arms of the study.

About the ARAMIS trial
The approval of darolutamide in Japan is based on the results of the ARAMIS trial, a randomized (2:1), double-blind, placebo-controlled, multi-center Phase III study which evaluated the safety and efficacy of the compound in patients with nmCRPC who are currently being treated with androgen deprivation therapy (ADT) and are at high risk for developing metastatic disease. In the clinical study, 1,509 patients were randomized in a 2:1 ratio to receive 600 mg of darolutamide orally twice daily or placebo along with ADT. Patients with a history of seizure were allowed in the study.

About darolutamide
Darolutamide is an androgen receptor inhibitor (ARi) with a distinct chemical structure that binds to the receptor with high affinity and exhibits strong antagonistic activity, thereby inhibiting the receptor function and the growth of prostate cancer cells. Darolutamide is also being investigated in a Phase III study in metastatic hormone-sensitive prostate cancer (ARASENS trial). Information about these trials can be found at www.clinicaltrials.gov.

The product is also approved in the U.S. and Brazil under the brand name Nubeqa. It is currently not approved by the European Medicines Agency.

About castration-resistant prostate cancer (CRPC)
Prostate cancer is the second most commonly diagnosed malignancy in men worldwide.2 In 2018, an estimated 1.2 million men were diagnosed with prostate cancer, and about 358,000 died from the disease worldwide.2 Prostate cancer is the fifth leading cause of death from cancer in men.2 Prostate cancer results from the abnormal proliferation of cells within the prostate gland, which is part of a man’s reproductive system.3 It mainly affects men over the age of 50, and the risk increases with age.4

Treatment options range from surgery to radiation treatment to therapy using hormone-receptor antagonists, i.e., substances that stop the formation of testosterone or prevent its effect at the target location.5 However, in nearly all cases, the cancer eventually becomes resistant to conventional hormone therapy.6

CRPC is an advanced form of the disease where the cancer keeps progressing despite ADT treatment, even when the amount of testosterone is reduced to very low levels in the body.1,7 In men with progressive nmCRPC, a rapid prostate specific antigen (PSA) doubling time has been consistently associated with reduced time to first metastasis and death.1

Sanofi Completes Acquisition of Synthorx, Inc.

On January 23, 2020 Sanofi reported the successful completion of its acquisition of Synthorx, Inc. ("Synthorx") for $68 per share in cash (Press release, Sanofi, JAN 23, 2020, View Source [SID1234553463]).

"The acquisition of Synthorx perfectly aligns with our R&D strategy, enhancing our position as an emerging leader in the area of oncology and immunology," says Paul Hudson, Chief Executive Officer, Sanofi. "We gain access to both great scientists and science with THOR-707, an engineered not-alpha IL-2 for the treatment of solid tumors which induces strong immunological responses in vivo, additional intriguing pre-clinical assets, and a powerful platform that complements our ongoing oncology and immunology research."

The tender offer for all of the outstanding shares of Synthorx common stock expired as scheduled at one minute after 11:59 p.m., Eastern Time, on Wednesday, January 22, 2020. The minimum tender condition and all of the other conditions to the offer have been satisfied and on January 23, 2020, Sanofi and its wholly owned subsidiary Thunder Acquisition Corp. ("Purchaser"), accepted for payment and will promptly pay for all shares validly tendered and not properly withdrawn.

Following its acceptance of the tendered shares, Sanofi completed its acquisition of Synthorx through the merger of Purchaser with and into Synthorx, pursuant to Section 251(h) of the General Corporation Law of the State of Delaware, with Synthorx continuing as the surviving corporation and becoming an indirect, wholly owned subsidiary of Sanofi.

In connection with the merger, all Synthorx shares not validly tendered in the tender offer have been converted into the right to receive the same $68 per share in cash, without any interest thereon and net of applicable withholding taxes, that would have been paid had such shares been validly tendered in the tender offer. Synthorx common stock will cease to be traded on the NASDAQ Global Select Stock Market.

Morgan Stanley & Co. acted as financial advisor to Sanofi and Weil, Gotshal & Manges LLP acted as its legal counsel. Centerview Partners LLC acted as exclusive financial advisor to Synthorx and Cooley LLP acted as its legal counsel.

EyePoint Pharmaceuticals Announces Preliminary Fourth Quarter and Full-Year 2019 Revenues

On January 23, 2020 EyePoint Pharmaceuticals, Inc. (NASDAQ: EYPT), a biopharmaceutical company committed to developing and commercializing innovative ophthalmic products reported preliminary, unaudited, total and net product revenue for the fourth quarter and full-year 2019. For the fourth quarter ended December 31, 2019, total revenues are estimated to be between $7.5 and $8.2 million and net product revenues are estimated to be between $6.9 and $7.6 million, a significant acceleration from net product revenues of $1.0 million reported for the third quarter ended September 30, 2019 (Press release, pSivida, JAN 23, 2020, View Source [SID1234553462]). For the full-year 2019, total revenues are estimated to be between $19.3 and $20.0 million and net product revenues are estimated to be between $15.8 and $16.5 million. The net product revenues acceleration in the fourth quarter of 2019 was driven by strong customer demand for both DEXYCU and YUTIQ.

"2019 was a year marked by significant achievement as evidenced by two successful commercial product launches, DEXYCU and YUTIQ," said Nancy Lurker, President & Chief Executive Officer of EyePoint. "We are very pleased by the sales acceleration in the fourth quarter for both products which positions the Company well for a strong 2020. Customer demand is building, physician acceptance continues to grow, and we will continue to execute on additional agreements with payors to expand access to our products. In parallel, we remain focused on advancing and enhancing our pipeline for areas of unmet need in ocular disease. "

Customer demand, represented as units purchased by physicians and ambulatory surgical centers (ASCs) from the Company’s distributors, showed continued strong unit growth for both products with estimated increases of 43% and 86% for YUTIQ and DEXYCU, respectively, in the fourth quarter of 2019 versus the third quarter of 2019. This growth was supported by the permanent and specific J-Code for YUTIQ in place as of October 1, 2019 and the execution of key agreements with payors and large ASCs during the period.

The difference between reported GAAP net product revenues and customer demand is due to the timing of distributor purchases from the Company based upon customer demand and distributor inventory levels from quarter to quarter. The Company also moved from a single distributor title model to a more traditional multi-distributor structure during the fourth quarter.

Net product revenue for YUTIQ is estimated to be between $4.1 and $4.5 million and between $11.4 and $11.8 million for the fourth quarter and full-year ended December 31, 2019, respectively.

Net product revenue for DEXYCU is estimated to be between $2.8 and $3.1 million and between $4.4 and $4.7 million for the fourth quarter and full-year ended December 31, 2019, respectively.

The Company estimates that it had cash and cash equivalents of approximately $22 million at December 31, 2019.

The preliminary fourth quarter and full-year 2019 revenue results included in this release were calculated prior to the completion of a review by the Company’s independent registered public accounting firm and are therefore subject to adjustment.

Fourth Quarter and Full Year 2019 Financial Results Conference Call

Eyepoint Pharmaceuticals will host a conference call and webcast to discuss fourth quarter and full-year 2019 financial results on Thursday, March 5, 2020 at 8:30 AM ET. To access the conference call, please dial (877) 312-7507 from the U.S. and Canada or (631) 813-4828 (international) at least 10 minutes prior to the start time and refer to conference ID 7314529. A live webcast will be available on the Investor Relations section of the corporate website at View Source A replay of the webcast will also be available on the corporate website.

Kura Oncology Announces Transition of Chief Medical Officer

On January 23, 2020 Kura Oncology, Inc. (Nasdaq: KURA), a clinical-stage biopharmaceutical company focused on the development of precision medicines for the treatment of cancer, reported that Antonio Gualberto, M.D., Ph.D., will step down as Head of Development and Chief Medical Officer to pursue other opportunities (Press release, Kura Oncology, JAN 23, 2020, View Source [SID1234553461]). Bridget Martell, M.A., M.D., currently Vice President of Clinical Development at Kura, has been named acting Chief Medical Officer while the company completes an executive search. Dr. Gualberto plans to serve in an advisory capacity during the transition, which will take effect on February 7, 2020.

"Antonio has been a key contributor to the tipifarnib development program over the past five years," said Troy Wilson, Ph.D., J.D., President and Chief Executive Officer of Kura Oncology. "He is responsible for much of the underlying translational work that identified the biomarkers of activity, including the discovery of the CXCL12 pathway as a target of tipifarnib, which enabled us to achieve clinical proof of concept in multiple solid tumor and hematologic indications and provided the framework for our ongoing registrational strategies. We thank him for his many contributions to the company and wish him continued success in his future endeavors.

"Now, as we continue our pre-commercial efforts and prepare for the company’s next phase of growth," Dr. Wilson continued, "we are very fortunate to have someone of Bridget’s caliber ready to step up and lead the clinical development organization. Bridget is a proven leader with broad expertise in drug development and a track record of success. Importantly, she has deep familiarity across our pipeline, having served as program lead for KO-539, our emerging menin-MLL inhibitor, for the past two years. I look forward to working even more closely with her in the months ahead as we seek to build on the potential opportunities for tipifarnib and maximize the value of our emerging pipeline."

Dr. Martell began working with Kura as a consultant in November 2017 and joined the company as Vice President of Clinical Development in June 2018, bringing more than 18 years of experience in clinical development, regulatory and medical affairs. She has served in leadership roles of increasing responsibility at Pfizer and Juniper Pharmaceuticals, where she contributed to the development and approval of a number of products, including the renal adjuvant indication for the oncology drug Sutent. Dr. Martell earned her B.S. in microbiology from Cornell University, her M.A. in molecular immunology from Boston University and her M.D. from the Chicago Medical School. She completed her internship and residency in Internal Medicine and was an Internal Medicine chief resident and RWJ Faculty Clinical Scholar at Yale University. She is board certified in both internal and addiction medicine.

FDA Grants Fast Track Designation to Gene Therapy Combination in EGFR-Mutant NSCLC

On January 23, 2020 Genprex reported the FDA has granted a Fast Track Designation to the immune-gene therapy Oncoprex in combination with the EGFR inhibitor osimertinib (Tagrisso) for the treatment of patients with EGFR-mutant non–small cell lung cancer (NSCLC) who have progressed after treatment with osimertinib alone (Press release, Genprex, JAN 23, 2020, View Source [SID1234553460]).

A clinical phase I/II trial will be initiated to evaluate Oncoprex plus osimertinib by Genprex. In addition, the company will initial a phase I clinical trial to evaluate the agent in combination with a checkpoint inhibitor.

"Genprex is excited to receive this important FDA designation," Rodney Varner, chairman and CEO of Genprex, said in a statement. "In addition to potentially facilitating and expediting our pathway to approval, we believe that this FDA designation validates our plan to commercialize Oncoprex immune-gene therapy in combination with EGFR inhibitors for the treatment of lung cancer."

Over 50 patients have been treated with the immune-gene therapy in phase I and phase II clinical trials through Genprex. According to the press release, the company believes the findings from these trials have been encouraging in terms of both safety and efficacy. The agent is made up of Tumor Suppressor Candidate 2 (TUSC2) gene complexed with a lipid nanoparticle. TUSC2 is an active agent in the immune-gene therapy.

"We hope that Fast Track Designation helps us bring our gene therapy to patients more rapidly and that our unique gene therapy platform is more widely recognized for its potential in cancer treatment," Varner said.

Lung cancer is the leading cause of cancer death worldwide, with more than 2 million new cases and 1.7 million deaths per year across the globe. Over 228,000 new cases of lung cancer occur in the United States annually, and 142,000 deaths are related to lung cancer each year. Approximately 84% of all cases of lung cancer are NSCLC, with a 5-year survival rate for metastatic lung cancer of less than 5%.

The FDA’s Fast Track Designation is granted to drugs demonstrating the ability to fulfill unmet medical needs for serious and life-threatening diseases. Should the combination of Oncoprex and the EGFR inhibitor receive approval, it will address the unmet need of patients with EGFR-mutant NSCLC who progress on osimertinib alone