On March 29, 2016 Bayer reported that the Ministry of Health, Labour and Welfare (MHLW) in Japan has granted marketing authorization for Xofigo (radium-223 dichloride, radium-223) for the treatment of patients with castration-resistant prostate cancer and bone metastases (Press release, Bayer, MAR 29, 2016, View Source [SID:1234510092]). The product is already approved in more than 40 countries worldwide, including the U.S. and the countries of the European Union (EU). Schedule your 30 min Free 1stOncology Demo! "A majority of men living with advanced prostate cancer develop bone metastases, resulting in symptoms that can interfere with daily life, such as tiredness, weakness or difficulty doing normal activities, and decreased overall survival," explained Dr. Hiroji Uemura, associate professor and department director of Urology and Renal Transplantation, Yokohama City University Medical Center. "Xofigo has an anti-tumor effect that enables us to directly target bone metastases and potentially prolong survival, a critical treatment goal for patients with advancing disease. In addition, it is expected to delay the time to the first symptomatic skeletal event."
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Prostate cancer is the second most commonly diagnosed malignancy in men worldwide, and its incidence is rising in Japan. Prostate cancer is the fifth leading cause of death from cancer in men worldwide and the sixth leading cause of death from cancer in Japanese men.
"We are pleased that Xofigo is now available in Japan, providing a new and innovative therapy with a proven clinical benefit to patients with advanced disease," said Dr. Joerg Moeller, member of the Executive Committee of Bayer AG’s Pharmaceutical Division and Head of Development. "Prostate cancer has a significant impact on men in Japan, and this is an important step in our ongoing commitment to deliver therapies to patient’s need."
The approval is based on data from the pivotal Phase III ALSYMPCA (ALpharadin in SYMptomatic Prostate CAncer) trial, as well as data from additional trials to evaluate the safety and efficacy of radium-223 in Japanese patients. At the interim analysis of the ALSYMPCA trial, radium-223 significantly improved overall survival (OS) [HR=0.681 (95% CI 0.542-0.857), p=0.00096]. The second analysis conducted after the study was unblinded showed a further improvement in OS for patients treated with radium-223 vs. placebo, with a median OS of 14.9 months vs. 11.3 months [HR=0.695 (95% CI 0.581-0.832)]. Median time to first symptomatic skeletal event, a secondary endpoint in ALSYMPCA, was 15.6 months for radium-223 versus 9.8 months for placebo [HR= 0.658 (95% CI 0.522-0.830)].
The most common adverse events (occurring at a rate of 25% or greater, all grades) in patients receiving radium-223 in the ALSYMPCA trial were bone pain (patients treated with radium-223: 51.7%, patients in the placebo group: 63.5%), nausea (35.5%, 33.9%), anemia (31.2%, 30.6%), fatigue (26.5%, 25.9%), diarrhea (25.7%, 15.0%). The most common hematologic laboratory abnormalities were anemia (31.2%, 30.6%), neutropenia (5.0%, 1.0%), pancytopenia (2.0%, 0%), thrombocytopenia (4.2%, 0.3%) and lymphocytopenia (0.8%, 0.3%).
ALSYMPCA Trial Design
The ALSYMPCA trial was a Phase III, randomized, double-blind, placebo-controlled international study of Xofigo with best standard of care vs. placebo with best standard of care in symptomatic castration-resistant prostate cancer (CRPC) patients with bone metastases. Interim and updated analyses of the trial showed Xofigo significantly improved overall survival.
About Castration-Resistant Prostate Cancer (CRPC) and Bone Metastases
The stage of prostate cancer is one of the most important factors in determining treatment options and the outlook for recovery. If prostate cancer spreads, or metastasizes, beyond the prostate gland, it often first grows into nearby tissues or lymph nodes before spreading to the bones.
CRPC is an advanced form of prostate cancer. Approximately nine in 10 patients with advanced prostate cancer (90 percent) develop bone metastases, impacting survival and quality of life. In fact, bone metastases lead to an increased risk of morbidity and death in patients with CRPC. Therefore, diagnosing and treating bone metastases at the earliest onset is critical for patients.
About Xofigo (radium-223 dichloride)
Xofigo is an alpha particle-emitting therapeutic anti-tumor pharmaceutical. The active ingredient in Xofigo is the alpha particle-emitting isotope radium-223, which mimics calcium and selectively targets bone, specifically areas of bone metastases, by forming complexes with the bone mineral hydroxyapatite. The high linear energy transfer of alpha emitters leads to a high frequency of double-strand DNA breaks in adjacent tumor cells, resulting in a potent cytotoxic effect. The alpha particle range from radium-223 is less than 100 micrometers, which minimizes damage to the surrounding normal tissue.
In countries of the EU, Xofigo is indicated for the treatment of adults with castration-resistant prostate cancer, symptomatic bone metastases and no known visceral metastases. Radium-223 is also being studied in additional trials for men with prostate cancer as well as in Phase II studies for women with breast cancer.
Author: [email protected]
Tagrisso™ (osimertinib) approved in Japan for patients with EGFR T790M mutation-positive metastatic non-small cell lung cancer
On March 29, 2016 AstraZeneca reported that the Japanese Ministry of Health, Labour and Welfare (MHLW) has approved Tagrisso (osimertinib, AZD9291) 80mg once-daily tablets for the treatment of patients with epidermal growth factor receptor (EGFR) T790M mutation-positive inoperable or recurrent non-small cell lung cancer (NSCLC) that is resistant to EGFR tyrosine kinase inhibitor (TKI) therapy (Press release, AstraZeneca, MAR 29, 2016, View Source [SID:1234510091]). Schedule your 30 min Free 1stOncology Demo! Sean Bohen, Executive Vice President, Global Medicines Development and Chief Medical Officer at AstraZeneca, said: "We continue to move at an unprecedented pace with osimertinib, with the full approval in Japan following closely the recent US and EU approvals. As first-in-class lung cancer treatment directed at the T790M mutation, we are delighted that this targeted medicine is now available to patients in Japan to address the existing unmet medical need."
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Dr. Tetsuya Mitsudomi, Division of Thoracic Surgery, Department of Surgery, Kinki University Faculty of Medicine said: "A significant proportion of Japanese patients with lung cancer have the EGFR mutation and about 60% of them are likely to develop the T790M resistance mutation following initial TKI treatment. Osimertinib enables us to respond to this disease progression in a precise and logical way as clearly demonstrated in clinical trials, with potential to make a meaningful difference to the lives of Japanese patients."
Approximately 30-40% of Asian patients with NSCLC have the EGFR mutation at diagnosis. Nearly two out of three patients with NSCLC whose disease progresses after treatment with an EGFR-TKI develop the T790M mutation, for which treatment options are currently limited. Osimertinib targets both the EGFR mutation involved in cancer development and T790M, a mutation that makes tumours resistant to existing treatment with EGFR-TKIs. Patients with EGFRm NSCLC, who experience disease progression, should be tested for their mutation status through a validated diagnostic test. AstraZeneca has collaborated with Roche to develop the cobas EGFR Mutation Test v2 as the companion diagnostic for osimertinib.
The Japanese approval is based on data from the two multinational AURA Phase II trials (AURA extension and AURA2), with 22% of patients enrolled from Japan. The studies demonstrated efficacy in patients who had progressed on or after treatment with an EGFR-TKI and whose tumours tested positive for the EGFR T790M mutation. The overall objective response rate (ORR, a measurement of tumour shrinkage) was 61.3% (95% CI: 54.2% to 68.1%) in AURA extension (n=199), and 70.9% (95% CI: 64.0% to 77.1%) in AURA2 (n=199) (1 May 2015 cut-off).
In the two AURA Phase II studies (n=411), the most commonly reported adverse events assessed by the investigator were rash/acne (37.7%), diarrhoea (36.5%), dry skin/eczema, etc. (28.5%), nail disorder including paronychia, etc (23.4%). In Japanese patients (n=80), the incidence of interstitial lung disease (ILD; including pneumonitis etc.), as assessed by the investigator, for all grades was 6.3% (1 May 2015 cut-off). Warnings and precautions include ILD, QT interval prolongation, hepatic impairment and haematological changes.
AstraZeneca has agreed a Risk Management Plan with the Japanese Health Authority.
The full Japanese approval was granted seven months after the New Drug Application submission in August 2015. The Japanese approval for osimertinib was granted under the Priority Review mechanism of the MHLW, in recognition of the submitted data and the life-threatening nature of the disease. The Japanese approval follows US FDA Accelerated Approval in November 2015 and European Commission conditional marketing authorisation in February 2016. Interactions with regulatory authorities in the rest of the world are ongoing.
NOTES TO EDITORS
About Non-Small Cell Lung Cancer (NSCLC)
Lung cancer is the leading cause of cancer death among both men and women, accounting for about one-third of all cancer deaths, and more than breast, prostate and colorectal cancers combined. Patients who have the EGFRm form of NSCLC, which occurs in 10-15% of NSCLC patients in Europe and 30-40% of NSCLC patients in Asia, are particularly sensitive to treatment with currently available EGFR-TKIs, which block the cell signalling pathways that drive the growth of tumour cells. However, tumours almost always develop resistance to treatment, leading to disease progression. In approximately two-thirds of patients treated with the approved EGFR-TKIs, gefitinib, erlotinib or afatinib, this resistance is caused by the secondary mutation, T790M.
About osimertinib
Osimertinib 80mg once-daily tablet is the first medicine indicated for the treatment of adult patients with metastatic EGFR T790M mutation-positive NSCLC. Non-clinical in vitro studies have demonstrated that osimertinib has high potency and inhibitory activity against mutant EGFR phosphorylation across the range of clinically relevant EGFRm and T790M mutant NSCLC cell lines, with significantly less activity against EGFR in wild-type cell lines.
Osimertinib is being compared with platinum-based doublet chemotherapy in the confirmatory AURA3 Phase III trial in patients with EGFR T790M-positive, locally advanced or metastatic NSCLC who have progressed after EGFR-TKI therapy. It is also being investigated in the adjuvant and metastatic first-line settings, including in patients with brain metastases, and in combination with other compounds.
8-K – Current report
On March 28, 2016 CASI Pharmaceuticals, Inc. (Nasdaq: CASI), a biopharmaceutical company dedicated to innovative therapeutics addressing cancer and other unmet medical needs, reported financial results for the three and 12 months ended December 31, 2015 (Filing, Q4/Annual, EntreMed, 2015, MAR 28, 2016, View Source [SID:1234510065]).
The Company reported a net loss of ($1.7 million), or ($0.05) per share, for the three months ended December 31, 2015. This compares with a net loss of ($1.6 million), or ($0.05) per share for the fourth quarter of 2014. The increase in net loss can be attributed to costs associated with enrolling patients in our Phase 2 Trial for ENMD-2076 in fibrolamellar carcinoma (FLC) during the fourth quarter of 2015, as well as increasing costs associated with expanding our China operations.
The net loss for the year ended December 31, 2015 was ($7.2 million), or ($0.22) per share, compared with a net loss of ($26.2) million or ($0.92) per share for 2014. The reported net loss for 2014 included a non-cash expense of $19.7 million for acquired in-process research and development associated with the September 2014 successful in-license of the rights for greater China of MARQIBO, ZEVALIN and EVOMELA from Spectrum Pharmaceuticals. The Company secured these rights primarily with equity and no cash up front. Excluding this non-cash expense, the net loss for 2014 would have been ($6.5 million), or ($0.23) per share.
As of December 31, 2015, CASI had cash and cash equivalents of $5.1 million. In January 2016, the Company completed an initial closing of a strategic financing and received net proceeds of $10.2 million.
Sara B. Capitelli, CASI’s Vice President, Finance and Principal Accounting Officer, commented, "Our research and development expenses for the fourth quarter increased over the prior year due to clinical trial costs associated with the initiation of our FLC trial in November 2015 and higher costs associated with our growing China operations during 2015. The decrease in general and administrative expenses compared with the previous year primarily reflects higher costs incurred in 2014 associated with our in-license of Spectrum products in 2014. We are continuing to execute our clinical development plans in the U.S. and China, and expect operating expenses to increase in 2016."
Further information regarding the Company, including its Annual Report on Form 10-K for the year ended December 31, 2015, can be found at www.casipharmaceuticals.com.
Ken K. Ren, Ph.D., Chief Executive Officer, commented, "Our financial results for the fourth quarter and year ended December 31, 2015 were as anticipated. In January 2016, we received $10.2 million net proceeds in an initial closing of a strategic financing which included common stock priced at $1.19 per share, the proceeds of which will support our product pipeline and advance our clinical and regulatory activities. Our import drug registration activities for MARQIBO, ZEVALIN and EVOMELA in China are ongoing, including the filing of our import registration trial application with CFDA for MARQIBO in January 2016. Our partner, Spectrum Pharmaceuticals, recently received FDA approval for EVOMELA which now allows us to advance the CFDA registration process towards an import registration trial and market approval in China. We continue to advance the clinical development of our lead proprietary drug candidate, ENMD-2076. Our Phase 2 trial in FLC is progressing well with 60% of patients already recruited for stage one of our 2-stage trial, and our Phase 2 trials in ovarian clear cell carcinoma, triple negative breast cancer and soft tissue sarcoma continue to progress along with correlative biomarker analysis. We continue to carefully manage our expenses, while achieving interim milestones towards our mission to become a fully-integrated pharmaceutical company with a rich product pipeline."
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OXiGENE Reports 2015 Financial Results
On March 28, 2016 OXiGENE, Inc. (Nasdaq:OXGN), a biopharmaceutical company developing vascular disrupting agents (VDAs) for the treatment of cancer, reported financial results for 2015 (Press release, OXiGENE, MAR 28, 2016, View Source [SID:1234510064]).
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For the year ended December 31, 2015, OXiGENE reported a net loss of $13.7 million compared to a net loss of $12.6 million for the year ended December 31, 2014. R&D expenses increased to $9.1 million in 2015 compared to $7.4 million in 2014, while general and administrative expenses decreased to $4.6 million in 2015 compared to $5.2 million in 2014.
At December 31, 2015, OXiGENE had cash of $27.3 million.
"During the second half of 2015 the Company worked to define and optimize a clinical plan that would most efficiently advance the development of CA4P, our lead investigational drug. We built our plan on results from a phase 2 clinical trial completed in 2014 in which CA4P, a novel vascular disrupting agent, dramatically improved platinum-resistant ovarian cancer treatment outcomes when combined with the approved anti-angiogenic agent bevacizumab (Avastin)," stated William D. Schwieterman, M.D., OXiGENE’s President and Chief Executive Officer. "As we begin 2016 our progress continues. The FDA recently approved our protocol for FOCUS, a phase 2/3 clinical trial designed to provide us with data to support the registration of CA4P as a new drug for the treatment of platinum-resistant ovarian cancer, and we remain on track to enroll patients in this study before mid-year. I am pleased that our year-end cash balance is expected to provide us with a sufficient runway to collect and present important data from FOCUS and other programs we have on-going."
About OXiGENE
Onconova Therapeutics, Inc. Reports Recent Business Highlights and Year-end 2015 Financial Results
On March 28, 2016 Onconova Therapeutics, Inc. (NASDAQ:ONTX), a clinical-stage biopharmaceutical company focused on discovering and developing novel products to treat cancer, reported a corporate update and reported financial results for the fourth quarter and year-ended December 31, 2015 (Press release, Onconova, MAR 28, 2016, View Source [SID:1234510063]).
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"Onconova is focused on the execution of the global INSPIRE trial of IV rigosertib. This trial is now enrolling higher-risk MDS patients at multiple U.S. sites and in Europe, and we are initiating additional clinical centers in the U.S. and abroad. Patients have been enrolled in the U.S. and Europe, and we are pleased that our Japan/Korea partner SymBio Pharmaceuticals has announced plans to enroll patients in INSPIRE in Japan," said Ramesh Kumar, Ph.D., President and CEO of Onconova. "In addition, based on the encouraging Phase 2 results for oral rigosertib in combination with azacitidine presented in December 2015, we are planning to define a regulatory path forward with the FDA this year."
Recent Business Highlights:
Development of Rigosertib IV in Higher-Risk MDS (HR-MDS)
The global INSPIRE trial is now enrolling patients in the United States and Europe. INSPIRE will be conducted in the United States, Europe, Australia, Israel, and Japan. The first patient in Europe was enrolled this month and sites in Japan are expected to open shortly. The first patient in this trial was enrolled in December 2015 at the MD Anderson Cancer Center.
Results from Onconova’s ONTIME trial were published in the top-tier, peer-reviewed journal, Lancet Oncology. The article, titled, "Rigosertib versus best supportive care for patients with high-risk myelodysplastic syndromes after failure of hypomethylating drugs (ONTIME): a randomised, controlled, phase 3 trial," appeared in the March 8, 2016 online edition of the journal.
Development of Oral Rigosertib in Combination with Azacitidine for MDS and AML Patients
The Phase 2 portion of an open label Phase 1/2 clinical trial, designated 09-08, evaluating oral rigosertib in combination with the approved dose of injectable azacitidine for patients with HR-MDS and AML is fully enrolled. The Phase 2 study included both front-line patients (i.e. not previously treated with HMAs) and patients after failure of treatment with an HMA. Positive interim data from the 09-08 trial were presented at the 2015 American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting in December 2015.
In the presentation at ASH (Free ASH Whitepaper), 30 MDS patients were evaluable for efficacy assessment per 2006 International Working Group, or IWG, criteria. Overall, 23 of 30 patients (77%) responded, including six patients who had complete remissions. Notably, 16 of 19 (84%) HMA-naïve patients had a response to the combination therapy and 7 of 11 (64%) patients whose disease had previously failed HMAs responded. Hematologic improvement was observed in 13 of 26 patients that were evaluable for this part of the analysis.
Patients received full dose (per label) of azacitidine and the recommended daily Phase 2 dose of oral rigosertib (560 mg in the morning and 280 mg in the afternoon). The combination of oral rigosertib and azacitidine was well tolerated, with a median duration of treatment of 4 months (range 1 to 27 months). Adverse events of Grade > 3 experienced across all cycles with the combination included thrombocytopenia (27%), neutropenia (22%), hypokalaemia (5%), hematuria (5%) and diarrhoea (3%).
Operational Update
On March 3, 2016, the Company received notice from Baxalta US Inc. of Baxalta’s election to terminate the September 2012 development and license agreement between Baxalta and the Company for convenience, effective August 30, 2016, following Baxalta’s reprioritization review. In accordance with the terms of the development and license agreement, upon termination, the rights that the Company had licensed to Baxalta will revert to the Company at no cost.
The Company recently cut its workforce by ~17% as an important step towards reducing its operating losses and cash expenditures. Additional cost-optimization measures are being considered for implementation over the next several months.
Upcoming Events
Enrollment of the first patient in the Phase 3 INSPIRE trial in Japan: 1H2016
Peer-reviewed publication of mechanism of action of rigosertib: 2Q2016
Presentation of updated Phase 2 data from oral rigosertib combination trial in MDS: 2Q2016
End of Phase 2 meeting with FDA to discuss data from oral rigosertib combination trial: 2H2016
2015 Financial Results
Cash, cash equivalents, and marketable securities as of December 31, 2015 totaled $19.8 million, compared to $43.6 million as of December 31, 2014. Onconova believes that its current cash and cash equivalents, together with anticipated contractual cost-sharing payments from Baxalta for a portion of the INSPIRE trial costs, and in consideration of the cost optimization measures previously noted, will be sufficient to fund its ongoing trials and operations into the first quarter of 2017.
Net loss was $24.0 million for the year ended December 31, 2015, compared to $63.8 million for the year ended December 31, 2014 due primarily to a 45% reduction in operating expenses and the recognition of deferred revenue in 2015.
Research and development expenses were $25.9 million for the year ended December 31, 2015, compared to $49.4 million for the year ended December 31, 2014,
General and administrative expenses were $9.5 million for the year ended December 31, 2015, compared to $15.1 million for the year ended December 31, 2014.