On January 8, 2019 Ono Pharmaceutical Co., Ltd. (Osaka, Japan; President, Representative Director, Gyo Sagara; "ONO") reported that it received a manufacturing and marketing approval of Demser (metyrosine) Capsule 250 mg ("Demser"), a tyrosine hydroxylase inhibitor, in Japan for the improvement of status of catecholamine excess secretion in patients with pheochromocytoma (Press release, Ono, JAN 8, 2019, View Source [SID1234605553]). Pheochromocytoma (PC) is a neuroendocrine tumor deriving from the adrenal medulla or the extraadrenal gland ganglion with 2,920 patients estimated in Japan*. Catecholamine excessively secreted from PC causes various symptoms, such as tachycardia, headache, palpitation, sweating, constipation, including hypertension. Sympatholytic drugs, α-blocker and β-blocker, for control of blood pressure and heart rate have been usually used to improve these symptoms. As there are many cases where surgical removal of tumors is not applicable in patients with locally invasive or metastatic malignant PC, a long-term therapy, such as radiotherapy and chemotherapy is required. The chronic continuation of catecholamine excess secretion may increase a risk of causing cardiovascular-related adverse events such as heart failure or fatal arrhythmia. Demser inhibits tyrosine hydroxylase related to the production of catecholamine, reduces catecholamine extremely secreted from PC, and alleviates symptoms due to catecholamine excess secretion. Demser is a promising drug with an efficacy in the improvement of the symptoms in patients who are not able to sufficiently control the symptoms with sympatholytic drugs. Demser is a product for which development companies were recruited in Japan at the "Review Committee on Unapproved or Off-label Drugs with High Medical Needs", established by the Ministry of Health, Labour and Welfare (MHLW), and ONO has been developing this product. In May 2015, the product was designated for the orphan drug by the MHLW. ONO obtained exclusive rights to develop and commercialize metyrosine in Japan for the treatment of PC (and conditions and symptoms related thereto), in accordance with the license agreement concluded in October 2013 with Valeant Pharmaceuticals North America LLC, an affiliate of Valeant Pharmaceuticals International, Inc. (In July 2018, the company name was changed to Bausch Health Companies Inc., "Bausch Health"). In the US, Bausch Health markets the product under the tradename of "Demser" in the indication of PC. *: "Actual condition survey and preparation of medical guideline of pheochromocytoma" Research Report 2009, Research Project on Overcoming Intractable Diseases Project being conducted by the Ministry of Health, Labour and Welfare Overview of Demser Capsule 250 mg Product Name Demser Capsule 250 mg Generic name (JAN) Metyrosine Indication Improvement of status of catecholamine excess secretion in patients with pheochromocytoma Dosage and administration Usually, for adults and children 12 years of age and older, start to administer 500 mg of metyrosine orally daily. When the effect is insufficient, titrate the dose by 250 mg or 500 mg daily at intervals of 3 days or more by monitoring the clinical course closely, and dosage should be adjusted under adequate observation of urinary catecholamine amount and symptoms of the patient. However, the maximum daily dose is 4,000 mg with the highest dose of 1,000 mg per dose at intervals of 4 hours or longer. The daily dose of 500 mg is divided twice a day, 750 mg three times a day and 1,000 mg four times a day. Manufacturer/distributor Ono Pharmaceutical Co., Ltd. Approval date January 8, 2019 Conditions for approval 1. Risk Management Plan should be designed appropriately implemented. 2. Because of the very limited number of patients treated with the product in Japanese clinical trials, a post-marketing use-results survey covering all cases should be performed until data on a certain minimum number of patients have been accumulated. Through these activities, actions necessary to ensure the proper use of the product should be taken by identifying the characteristics of patients to be treated with the product and collecting safety and efficacy data as soon as possible.

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On January 8, 2019 CSPC Pharmaceutical Group Ltd. agreed to acquire Hong Kong-based Yong Shun Technology Development for about 252.9 million yuan (Press release, CSPC Pharmaceutical, JAN 8, 2019, View Source [SID1234605494]). CSPC unit Dragon Merit Holdings Ltd. will acquire all issued shares of Yong Shun, subject to certain conditions. CSPC said the deal is in line with its strategy to seek acquisition targets with strong research and development capabilities in the biopharmaceutical drug market. As of Jan. 7, US$1 was equivalent to 6.85 yuan.

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On January 8, 2019 ImmunoGen, Inc. (Nasdaq: IMGN), a leader in the expanding field of antibody-drug conjugates (ADCs) for the treatment of cancer, reported the sale of its residual rights to receive royalty payments on commercial sales of Kadcyla (ado-trastuzumab emtansine) to OMERS, the defined benefit pension plan for municipal employees in the Province of Ontario, Canada, for $65 million (Press release, ImmunoGen, JAN 8, 2019, View Source [SID1234553884]).

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"ImmunoGen played a key role in the generation and early development of Kadcyla, the first ADC approved for the treatment of HER2-positive breast cancer, and we are pleased to see the continued progress of this important therapy in the market," said Mark Enyedy, President and Chief Executive Officer. "As ImmunoGen evolves into a fully-integrated company with our proprietary portfolio, this transaction further strengthens our balance sheet as we execute on our strategic priorities and work to deliver more good days to people living with cancer."

This transaction entails the sale of the residual interest held by ImmunoGen from a prior transaction with Immunity Royalty Holdings, L.P. (IRH). In 2015, ImmunoGen announced a $200 million non-dilutive royalty transaction through which ImmunoGen sold the right to receive 100% of the royalty revenue on Kadcyla commercial sales to an undisclosed threshold amount, subject to certain conditions. Once the applicable threshold was met, ImmunoGen would receive 85% of the Kadcyla royalty revenue and the original purchaser would receive 15% for the remaining term of the royalty. With this transaction, OMERS now owns 100% of ImmunoGen’s rights to receive Kadcyla royalties.

MTS Health Partners, L.P. acted as exclusive financial advisor to ImmunoGen and Mintz, Levin, Cohn, Ferris, Glovsky and Popeo, P.C. acted as special transactional counsel to ImmunoGen.

ABOUT KADCYLA ROYALTIES

Genentech, a member of the Roche Group, developed Kadcyla (ado-trastuzumab emtansine) using ADC technology licensed from ImmunoGen under a 2000 agreement established between the companies. This agreement entitles ImmunoGen to receive royalties ranging from 3-5% on Kadcyla sales in countries where ImmunoGen holds valid patents covering Kadcyla, and 2% in countries without relevant ImmunoGen patents. ImmunoGen is entitled to receive royalties on commercial Kadcyla sales in each country for ten years after the launch of Kadcyla in that country. This period extends to twelve years for each country in which ImmunoGen has valid claims in relevant patents on the tenth anniversary of the commercial launch of Kadcyla in that country.

On January 8, 2019 Astellas Pharma Inc. (TSE: 4503, President and CEO: Kenji Yasukawa, Ph.D., "Astellas") reported that gonadotrophin-releasing hormone (GnRH) receptor antagonist, Gonax received approval for partial changes for the additional dosage and administration of Gonax for the treatment of prostate cancer at 12-week intervals, and obtained manufacturing and marketing authorization for Gonax 240 mg in Japan (Press release, Astellas, JAN 8, 2019, View Source [SID1234534620]).

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Gonax is a GnRH receptor antagonist with a subcutaneously injectable formulation. Astellas acquired exclusive development and commercialization rights of Gonax for the use of prostate cancer treatment in Japan from Ferring Pharmaceuticals in January 2006, and launched Gonax for the indication of prostate cancer in Japan in October 2012.

GnRH is a hormone synthesized and released from the hypothalamus in the brain and is involved in the production of the male hormone testosterone thorough binding to the GnRH receptors in the pituitary gland. Although testosterone is an important hormone that plays a central role in the maintenance of male function, it also stimulates prostate cancer to grow and to spread out and in result, often aggravates symptoms in prostate cancer patients. Gonax competitively inhibits the binding of GnRH to the GnRH receptors and controls the growth of prostate cancer by suppressing the testosterone.

Astellas believes that adding the maintenance dose of Gonax 480 mg at 12-week intervals to the maintenance dose of Gonax 80 mg at 4-week intervals will improve convenience for patients and reduce the burden on patients and further contribute to the treatment of prostate cancer.

Astellas reflected the impact from this approval in its financial forecasts of the current fiscal year ending March 31, 2019.

On January 8, 2019 MediciNova, Inc., a biopharmaceutical company traded on the NASDAQ Global Market (NASDAQ:MNOV) and the JASDAQ Market of the Tokyo Stock Exchange (Code Number: 4875), reported that the first glioblastoma patient has enrolled in the clinical trial of MN-166 (ibudilast) in combination with temozolomide (TMZ, Temodar‑) for the treatment of recurrent glioblastoma (GBM) (Press release, MediciNova, JAN 8, 2019, View Source;p=RssLanding&cat=news&id=2382746 [SID1234532592]). The principal investigators are Patrick Y. Wen, M.D., Professor of Neurology, Harvard Medical School and Director, Neuro-Oncology Division at the Dana-Farber Cancer Institute (DFCI) in Boston, and Kerrie McDonald, Ph.D., Associate Professor and Head of Biomarkers and Translational Research at the Lowy Cancer Research Centre, University of New South Wales, Australia.

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The scientific rationale for this clinical trial is based on positive results from preclinical studies conducted by Dr. McDonald and her team. MN-166 (Ibudilast) and temozolomide (TMZ) combination treatment significantly increased GBM cell apoptosis and cell cycle arrest in an in-vitro study. Combination treatment of MN-166 (ibudilast) with TMZ resulted in significantly extended survival times compared to TMZ monotherapy in a GBM animal model study with complete tumor regression observed in two out of 16 mice. This is the first clinical trial to evaluate the safety, tolerability and preliminary efficacy of MN-166 (ibudilast) in combination with temozolomide for the treatment of recurrent GBM.

Patrick Y. Wen, M.D., principal investigator, commented, "We are very excited to study ibudilast with TMZ combination treatment as we believe ibudilast’s mechanisms of action and good penetration of the blood-brain barrier could benefit patients with recurrent GBM."

Kerrie McDonald, Ph.D., Associate Professor, University of New South Wales, Australia, commented, "Earlier studies indicate that macrophage migration inhibitory factor (MIF) and phosphodiesterase (PDE)-4 may factor in proliferation of GBM tumors. MIF was found to be highly expressed within GBM cells, and especially around necrotic areas and in close proximity to blood vessels. Ibudilast in combination with TMZ resulted in significant blockage of MIF expression, increased apoptosis, and longer survival in vivo."

Yuichi Iwaki, MD, PhD, President and Chief Executive Officer of MediciNova, Inc., commented, "We are very pleased that enrollment has commenced for this trial at Dana-Farber Cancer Institute, one of the most highly rated cancer treatment institutions in the U.S. We believe MN-166 offers a novel approach to treating GBM, a highly lethal form of cancer that develops from glial cells."

About the Clinical Trial

This Phase 1/2 clinical trial is divided into a dose-escalation phase (Part 1) followed by a fixed-dose phase (Part 2). A total of 15-18 adult subjects are planned to be enrolled in Part 1 and approximately 32 subjects are planned to be enrolled in Part 2. Part 1 will evaluate the safety and tolerability of MN-166 (ibudilast) when given in combination with TMZ, and determine the dose of MN-166 (ibudilast) to be used in Part 2 of the study. Part 2 will evaluate the efficacy of MN-166 (ibudilast) and temozolomide combination treatment in patients with recurrent GBM as measured by the proportion of patients who are progression-free at 6 months. Other outcome measures include the evaluation of overall survival, response rate, and median six-month progression-free survival.

About Glioblastoma

According to the American Association of Neurological Surgeons, GBM is a devastating brain cancer that typically results in death in the first 15 months after diagnosis. GBM develops from glial cells (astrocytes and oligodendrocytes) and rapidly grows and commonly spreads into nearby brain tissue. GBM is classified as Grade IV, the highest grade, in the World Health Organization (WHO) brain tumor grading system. The American Brain Tumor Association reports that GBM represents 15% of all brain tumors and 56% of all gliomas and has the highest number of cases of all malignant tumors, with an estimated 12,760 new cases predicted for 2018. Despite decades of advancements in neuroimaging, neurosurgery, chemotherapy, and radiation therapy, only modest improvements have been achieved and the prognosis has not improved for individuals diagnosed with GBM. Median survival is 14.6 months and two-year survival is 30%. Approximately 5% of GBM patients survive longer than 36 months.

About MN-166 (ibudilast)
MN-166 (ibudilast) is a first-in-class, orally bioavailable, small molecule macrophage migration inhibitory factor (MIF) inhibitor and phosphodiesterase (PDE) -4 and -10 inhibitor that suppresses pro-inflammatory cytokines and promotes neurotrophic factors. It attenuates activated glial cells, which play a major role in certain neurological conditions. MN-166 (ibudilast)’s anti-neuroinflammatory and neuroprotective actions have been demonstrated in preclinical and clinical studies, which provide the rationale for treatment of progressive multiple sclerosis (MS) and other neurological diseases such as amyotrophic lateral sclerosis (ALS), substance abuse/addiction and glioblastoma (GBM). MediciNova is developing MN-166 for progressive MS and other neurological conditions such as ALS, substance abuse/addiction, chemotherapy-induced neuropathy, and glioblastoma. MediciNova has a portfolio of patents which cover the use of MN-166 (ibudilast) to treat various diseases including progressive MS, ALS, and drug addiction.