On January 8, 2016 Otsuka Pharmaceutical Co., Ltd. (Headquarters: Chiyoda-ku, Tokyo; President and CEO: Tatsuo Higuchi; "Otsuka")reported that it has filed the NDA in Japan for "ponatinib (brand name outside Japan is Iclusig), a known tyrosine kinase inhibitor (TKI) developed by ARIAD Pharmaceuticals, Inc. (Headquarters: Massachusetts, United States; "ARIAD") used to treat resistant and intolerant chronic myeloid leukemia (CML) and Philadelphia-chromosome positive acute lymphoblastic leukemia (Ph+ ALL) (Press release, Otsuka, JAN 8, 2016, View Source [SID:1234508699]). Schedule your 30 min Free 1stOncology Demo! ARIAD conducted a multicenter Phase I / II trial in Japan to confirm efficacy, safety and tolerability of ponatinib. Otsuka filed the NDA based on these results and the results of overseas clinical trials. Furthermore, ponatinib was designated in Japan to be an orphan drug in September 2015.
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Ponatinib is a TKI discovered and developed by ARIAD that targets BCR-ABL expressed in CML and Ph+ ALL. This drug is a new chemically synthesized oral TKI, and is specifically designed to inhibit unmutated BCR-ABL as well as T315I mutation, a mutant-type BCR-ABL that manifests and induces resistance after patients are treated with other TKIs. Ponatinib demonstrates efficacy in currently available TKI-resistant and in patients who are intolerable CML as well as relapsed or refractory Ph+ ALL, but it also demonstrates efficacy for isoforms of BCR-ABL that carry mutations that confer resistance to treatment, including the T315I mutation, which has been associated with resistance to other approved TKIs. Ponatinib was approved by the US FDA in December 2012, and was approved in Europe in July 2013.
In Japan, CML occurs in approximately 1 out of 100,000 people among all age groups. It is estimated that there are approximately 11,000 patients.*3 Although the mortality rate has decreased with the advancement of TKI treatment, the number of patients is steadily increasing with an aging population. Initial symptoms are rarely seen in CML patients from disease onset to the chronic phase (5-6 years); however, white blood cell count and the blast cell ratio increase and, as the disease progresses, patients begin experiencing symptoms such as general malaise, weight loss, and bloating due to hepatosplenomegaly. In the accelerated phase (6-9 months), patients experience bone pain and exacerbation of hepatosplenomegaly; in the blast phase (3-6 months), patients experience anemia, bleeding tendencies, infections, etc. For CML, symptoms gradually worsen and risk of treatment resistance increases as the disease progresses*4. In contrast, Ph+ALL is seen in pediatric and elderly patients, and prognosis is extremely poor for patients who relapse after receiving initial ALL treatment and is an area where needs are still unmet.*5,6
Although TKI is used as a first-line drug for CML and Ph+ ALL, resistance to treatment can develop as the disease progresses because of amplification, overexpression or mutation of BCR-ABL genes, which are causal factors of the disease. In such cases, an adequate patient response to therapy may not be obtained even after several TKI products are used. In addition, there are patients who must discontinue treatment as they become intolerant of the side effects of other TKIs. A new TKI treatment is desired in Japan and other Asian countries in order to treat such resistant or intolerant patients.
Otsuka is currently expanding its product portfolio and is focusing on CNS (neuropsychiatry), cardiovascular, ophthalmology, and oncology fields. The company will continue to develop and commercialize pharmaceuticals aimed to improve survival of hematological cancer patients with insufficient treatment options by undertaking operations to provide a wide range of products from diagnostics to treatment.
Author: [email protected]
Roche presents updated results for investigational cancer immunotherapy atezolizumab in advanced bladder cancer
On January 8, 2015 Roche (SIX: RO, ROG; OTCQX: RHHBY) reported updated results from the pivotal phase II study, IMvigor 210, of the investigational cancer immunotherapy atezolizumab (MPDL3280A) in people with locally advanced or metastatic urothelial carcinoma (mUC) (Press release, Hoffmann-La Roche , JAN 8, 2016, View Source [SID:1234508698]). Schedule your 30 min Free 1stOncology Demo! Median overall survival (mOS) in this heavily pre-treated population was 11.4 months [95% CI: 9.0, NE] in people with higher levels of PD-L1 expression, and 7.9 months [95% CI: 6.6, 9.3] in the overall study population. The study also showed that 84% (n=38/45) of people who responded to atezolizumab continued to respond regardless of their PD-L1 status, when the results were assessed with longer median follow-up of 11.7 months. Median duration of response has not yet been reached. Atezolizumab was well tolerated and adverse events were consistent with those observed in previous updates. These data were presented at the 2016 Genitourinary Cancers Symposium of the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) (ASCO GU).1
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"It is encouraging to see that the majority of people with advanced bladder cancer who responded to atezolizumab maintained their response with longer follow up," said Sandra Horning, MD, Chief Medical Officer and Head of Global Product Development. "We are looking forward to sharing these results with the US FDA and other health authorities in the hope that we may bring atezolizumab to treating physicians and their patients as soon as possible."
Roche is planning to submit these data imminently to Global health authorities and the U.S. Food and Drug Administration (FDA) under Breakthrough Therapy designation. This designation is designed to expedite the development and review of medicines that may demonstrate substantial improvement over existing therapies for serious diseases.
About the IMvigor 210 study
IMvigor 210 is an open-label, multicentre, single-arm phase II study that evaluated the safety and efficacy of atezolizumab in people with locally advanced or mUC, regardless of PD-L1 expression. People in the study were enrolled into one of two cohorts. Cohort 1 comprised those who had received no prior therapies for locally advanced or mUC, but who were ineligible for first-line cisplatin-based therapy. The results for this cohort are not yet mature. Cohort 2, for which updated results were announced today, included people whose disease had progressed during or following previous treatment with a platinum-based chemotherapy regimen(heavily pretreated), 41 percent of people in the study had 2 or more treatments in the metastatic setting. People received a 1200-mg intravenous dose of atezolizumab on day 1 of 21-day cycles until progressive disease (Cohort 1) or loss of clinical benefit (Cohort 2).
Co-primary endpoints of the study included confirmed RECIST v1.1 ORR per central IRF and investigator-assessed modified RECIST ORR. Secondary endpoints included duration of response, overall survival, progression-free survival and safety. People were selected by histology, prior lines of therapy and PD-L1 expression on tumour-infiltrating immune cells (IC), using an investigational immunohistochemistry test that is being developed by Roche Tissue Diagnostics.
In addition to IMvigor 210, Roche has an ongoing randomised phase III study, IMvigor 211, comparing atezolizumab with standard-of-care chemotherapy in people who have mUC that worsened after initial treatment. All studies include the evaluation of a companion test developed by Roche Tissue Diagnostics to determine PD-L1 status.
About metastatic urothelial cancer
Metastatic urothelial cancer is associated with a poor prognosis and limited treatment options. It is a disease that has seen no major advancements for nearly 30 years. Urothelial cancer is the ninth most common cancer worldwide, with 430,000 new cases diagnosed in 2012, and it results in approximately 145,000 deaths globally each year. Men are three times more likely to suffer from urothelial cancer compared with women, and it is also three times more common in developed countries than in less developed countries.
About atezolizumab
Atezolizumab (also known as MPDL3280A) is an investigational monoclonal antibody designed to target and bind to a protein called PD-L1, which is expressed on TCs and tumour-infiltrating ICs. PD-L1 interacts with PD-1 and B7.1, both found on the surface of T cells, causing inhibition of T cells. By blocking this interaction, atezolizumab may enable the activation of T cells, restoring their ability to effectively detect and attack tumour cells.
Apogenix Receives First Milestone Payment from CANbridge Licensing Agreement and Signs Amendment to Include Taiwan
On January 7, 2016 Apogenix, a biopharmaceutical company developing next generation immuno-oncology therapeutics, reported that the first milestone of its licensing agreement with CANbridge Life Sciences for the development and commercialization of lead immuno-oncology candidate APG101 in China, Macao, and Hong Kong has been reached, triggering a milestone payment. In addition, Apogenix and CANbridge have signed an amendment to expand the licensed territories to include Taiwan (Press release, Apogenix, JAN 7, 2016, View Source [SID1234524583]). Apogenix will continue to develop APG101 in all other territories.
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An initial biomarker study conducted by CANbridge in Chinese glioblastoma patients revealed a high degree of CD95 ligand expression and confirmed the expression pattern seen in Apogenix’ phase II proof of concept trial in patients with recurrent glioblastoma. APG101 is a CD95 ligand inhibitor which restores the immune response against tumors and inhibits invasive tumor cell growth. In Apogenix’ phase II trial, glioblastoma patients expressing a certain biomarker associated with the CD95 ligand experienced the greatest benefit from treatment with APG101. The median overall survival rate in biomarker-positive patients treated with APG101 more than doubled to 16 months compared to patients treated with radiotherapy alone.
"We are very pleased with CANbridge’s progress and the achievement of the first milestone ahead of schedule," said Thomas Hoeger, Ph.D., Chief Executive Officer of Apogenix. "Based on the commitment demonstrated by CANbridge and the excellent collaboration throughout our partnership, we have expanded the licensed territories to include Taiwan. We look forward to CANbridge initiating a phase I/II trial with APG101 in newly-diagnosed glioblastoma patients in Taiwan in the second half of this year."
OncoResponse and Oregon Health & Science University Collaborate to Identify Novel Immuno-Oncology Targets
On January 7, 2016 OncoResponse, an immuno-oncology antibody discovery company, and the Knight Cancer Institute at Oregon Health & Science University reported a collaboration to identify antibodies against novel targets in elite responders to cancer immunotherapy (Press release, OncoResponse, JAN 7, 2016, View Source [SID1234516435]). The agreement provides OncoResponse with access to OHSU patient samples in two cancer indications, prostate cancer and chronic myeloid leukemia (CML), for immune repertoire screening to identify antibodies with exceptional reactivity from patients who have elite responses to cancer immunotherapies.
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"By interrogating the humoral response of patients who have responded exceptionally well to immunotherapy, we can identify rare cancer-fighting antibodies and novel targets that may lead to the development of improved cancer treatments," said Clifford J. Stocks, CEO of OncoResponse. "This collaboration will allow us access to invaluable patient sample sets that will undoubtedly be instrumental to the understanding of the immune response to cancer."
Using a validated platform technology to rapidly screen antibodies made by the human immune system, OncoResponse scientists will identify those with exceptional reactivity and leverage this knowledge to identify potential targets for novel therapeutic development. Financial terms of the agreement were not disclosed.
"We are deeply committed to the development of improved cancer treatments for patients in need," said Tomasz Beer, M.D., deputy director, OHSU Knight Cancer Institute. "This collaboration will provide valuable data that will allow us to develop a better understanding of what makes certain treatments successful and will inform the development of new therapies that have the potential to significantly impact patients’ lives."
Eureka Therapeutics Announces Exclusive License Agreement between Memorial Sloan Kettering Cancer Center and Juno Therapeutics for Use of a Novel, Fully-Human MUC16 Binder in CAR T Cell Immunotherapy
On January 7, 2016 Eureka Therapeutics, Inc. reported that Memorial Sloan Kettering Cancer Center and Juno Therapeutics, Inc. (Nasdaq: JUNO) have entered into an exclusive license agreement for a novel, fully-human binding domain targeting MUC16 to be used for the potential development and commercialization of chimeric antigen receptor (CAR) cell therapies for patients with MUC16 positive cancers, including ovarian, fallopian tube, and primary peritoneal cancers (Press release, Eureka Therapeutics, JAN 7, 2016, View Source [SID:SID1234515201]). The binder was developed under a collaboration agreement between Eureka Therapeutics and Memorial Sloan Kettering Cancer Center.
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"We are excited that Juno Therapeutics, a leader in CAR and TCR technologies, will pursue the development of this binding domain as a CAR cell therapy," said Dr. Cheng Liu, President and Chief Executive Officer of Eureka Therapeutics. "CAR cell therapy has shown promising potential for treating hematologic malignancies, and Eureka is working to accelerate the potential of the technology in a broader array of patients by developing antibodies that can recognize solid tumor antigens with the stringency required for CAR immunotherapy."
"We are pleased to enter into this agreement, as we continue to pursue the development of fully-human binding domains, with the goal of optimizing cell persistence and potential patient benefit of our engineered cells," said Mark Frohlich, M.D., Juno’s Executive Vice President, Development and Portfolio Strategy. "We opened a Phase I trial for our MUC16/IL-12 armored CAR product candidate in 2015, and if the safety and efficacy results are promising, this collaboration will allow us to more rapidly transition from the current murine binding domain to a fully-human binding domain."
Under the terms of the exclusive license agreement, Memorial Sloan Kettering granted Juno Therapeutics an exclusive, worldwide license, under both Memorial Sloan Kettering’s and Eureka’s rights to certain MUC16 binding domains, to develop and commercialize the MUC16 binding domains as part of CAR cell therapies for all indications. In return, Memorial Sloan Kettering will receive an upfront payment and potential future payments upon achievement of certain development, regulatory, and sales milestones, and annual net sales royalty payments. Pursuant to the collaboration agreement between Eureka and Memorial Sloan Kettering, Eureka will receive a portion of these payments from Memorial Sloan Kettering. Juno will fund additional development and commercialization activities.