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Takeda Submits New Drug Application for Ixazomib for Patients with Relapsed/Refractory Multiple Myeloma

On July 14, 2015 Takeda Pharmaceutical reported that a New Drug Application (NDA) has been submitted to the United States (U.S.) Food and Drug Administration (FDA) for ixazomib, an investigational oral proteasome inhibitor for the treatment of patients with relapsed and/or refractory multiple myeloma (Press release, Takeda, JUL 14, 2015, View Source [SID:1234506334]).

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The NDA submission was based on the pivotal Phase 3 trial TOURMALINE-MM1, an international, randomized, double-blind, placebo controlled clinical trial of 722 patients designed to evaluate the superiority of ixazomib plus lenalidomide and dexamethasone over placebo plus lenalidomide and dexamethasone in adult patients with relapsed and/or refractory multiple myeloma. Patients continue to be treated in this trial and evaluated for long-term outcomes.

"The TOURMALINE-MM1 study is the first in a series of five Phase 3 trials within our ixazomib program, which is designed to evaluate whether sustained therapy with a proteasome inhibitor, delivered orally, improves the clinical outcomes of patients living with multiple myeloma or with systemic light-chain (AL) amyloidosis," said Andrew Plump, M.D., Ph.D., Takeda’s Chief Medical and Scientific Officer. "This submission marks an important step in Takeda’s ongoing commitment to innovation for patients living with multiple myeloma. We thank the patients and their families for placing their trust in us and in ixazomib as they continue to participate in the TOURMALINE program."

"Continuous treatment is emerging as a standard of care in multiple myeloma with demonstrable improvement in long-term outcomes," commented Paul Richardson, M.D., Clinical Program Leader and Director of Clinical Research, Jerome Lipper Multiple Myeloma Center Institute Physician at Dana-Farber Cancer Institute. "Proteasome inhibition has become an essential component of treatment, but there are logistical challenges for patients with both intravenous and subcutaneous approaches, and especially in the absence of an effective oral option. If approved, ixazomib, with the convenience of once-a-week oral administration as well as promising efficacy, should provide a very meaningful advance for our patients."

This is the first regulatory submission for ixazomib. Additional filings are planned to begin in Europe and other countries later this year.

Licensing Agreement for Agent Targeting Prevention of Recurrence of Hepatocellular Carcinoma “Peretinoin”

On July 14, 2015 Kowa and Chugai reported that they have entered into license agreement of "peretinoin (development code: NIK-333)" for which Kowa is currently conducting clinical development for prevention of recurrence of hepatocellular carcinoma (Press release, Chugai, JUL 14, 2015, View Source [SID:1234506327]).

Under this agreement, Kowa will acquire the marketing authorization, and Chugai will have the exclusive marketing rights of the product supplied by Kowa in Japan. Under the terms of the agreements, Kowa will receive an upfront fee and milestone payments from Chugai.

Approximately 40,000 people are newly diagnosed with primary liver cancer in Japan each year, with approximately 30,000 deaths, and it is the fifth leading cause of death due to cancer. Hepatocellular carcinoma accounts for approximately 94% of primary liver cancer. The rate of recurrence of hepatocellular carcinoma after radical surgery is reported to be 30.1% in the first year, 62.3% in the third year, and 79.0% in the fifth year respectively.

Peretinoin is an oral acyclic retinoid with a vitamin A-like structure mainly targeting the retinoid nuclear receptor. It is the first drug in the world aiming at preventing the recurrence of hepatocellular carcinoma.

Through the introduction of peretinoin to the market, Kowa and Chugai expect to contribute to patients, their families, and medical professionals by fulfilling unmet medical needs and providing new treatment options.

IRESSA approved by US FDA for first-line treatment of patients with advanced EGFR mutation-positive non-small cell lung cancer

On July 13, 2015 AstraZeneca today reported that the US Food and Drug Administration (FDA) has approved IRESSA (gefitinib) tablets, 250mg once daily, for the first-line treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumours have epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 (L858R) substitution mutations, as detected by an FDA-approved test (Press release, AstraZeneca, JUL 13, 2015, View Source [SID:1234506348]).

IRESSA is an oral, EGFR tyrosine kinase inhibitor (TKI), which works by blocking the activity of the EGFR tyrosine kinase enzyme responsible for regulating signalling pathways implicated in the growth and survival of cancer cells. IRESSA was granted Orphan Drug Designation by the FDA in August 2014 for the treatment of EGFR mutation-positive NSCLC.

Antoine Yver, Head of Oncology, Global Medicines Development at AstraZeneca said: "The approval of IRESSA provides physicians and patients in the US with a new choice of first-line treatment for metastatic non-small cell lung cancer. AstraZeneca is at the forefront of research into targeted therapies for EGFR mutated lung cancer and is committed to improving the outlook for patients at all stages of the disease."

AstraZeneca has partnered with QIAGEN to provide the therascreen EGFR companion diagnostic test for IRESSA in the US. The test rapidly identifies EGFR mutation status through a tumour tissue sample, in order to guide the use of IRESSA in the treatment of patients with metastatic NSCLC.

The FDA approval of IRESSA is based on data from the Phase IV IFUM1 (IRESSA Follow-Up Measure) study, assessing IRESSA as a first-line treatment for Caucasian patients with locally advanced or metastatic EGFR mutation-positive NSCLC. This was supported by results from the IPASS2 (IRESSA Pan-ASia Study) clinical trial.

IRESSA is approved in 91 countries for the treatment of adult patients with locally advanced or metastatic EGFR mutation-positive NSCLC. The safety profile of IRESSA is well established through a large, global clinical programme and extensive real world evidence. The most commonly reported adverse events for IRESSA are diarrhoea and skin reactions including rash, acne, dry skin and pruritus.

AstraZeneca is also studying IRESSA in combination with other investigational medicines, including the company’s anti-PD-L1 monoclonal antibody, durvalumab (MEDI4736) to assess its potential as a combination treatment for a broader range of lung cancer patients.

OncoGenex Announces Custirsen Phase 3 "ENSPIRIT" Trial Continues Following Completion of Final Futility Survival Analysis

On July 13, 2015 OncoGenex Pharmaceuticals reported that its Phase 3 ENSPIRIT trial evaluating custirsen in the treatment of advanced or metastatic non-small cell lung cancer (NSCLC) is continuing as planned per the recommendation of an Independent Data Monitoring Committee (IDMC) (Press release, OncoGenex Pharmaceuticals, JUL 13, 2015, View Source [SID:1234506323]). This decision was based upon completion of the second and final planned interim futility analysis.

"Passing this important milestone strengthens our belief in custirsen and its potential to provide clinical benefit in this patient population with advanced disease and limited treatment options," said Scott Cormack, President and CEO of OncoGenex. "While the ENSPIRIT results remain blinded, this news is particularly exciting following the protocol amendment, which set a high bar for continuing the trial."

Two interim analyses were originally planned to evaluate whether to stop the trial for futility. OncoGenex filed an amendment with the U.S. Food and Drug Administration amending the statistical design and analysis plan that included a more rigorous and expedient evaluation of the potential survival benefit associated with custirsen in NSCLC. Based on current enrollment, initial ENSPIRIT results could be available in the second half of 2016.

"While advancements have been made for NSCLC patients with specific mutations and biomarkers, treatment resistance continues to be a challenge and combination chemotherapy remains the therapeutic backbone for the majority of patients with lung cancer," said Cindy Jacobs, PhD, MD, Chief Medical Officer and Executive Vice President of OncoGenex. "As we continue to gain a better understanding of the patients most likely to benefit from custirsen, we look forward to the results of our two Phase 3 trials in the lung and prostate cancer settings."

Recent findings from a retrospective analysis of data from the Phase 3 SYNERGY trial showed a benefit with custirsen therapy when added to first-line docetaxel chemotherapy in men with metastatic castrate-resistant prostate cancer (CRPC) who had a poor prognosis. The analysis showed that over 40 percent of men in the trial had at least 2 of the 5 common risk factors for poor prognosis. In these men, the analysis found a 27 percent lower risk of death when custirsen was used in combination with first-line docetaxel compared to docetaxel alone. Subject to finalizing the pending protocol amendment, timing for the final analysis of the poor prognosis subpopulation in the Phase 3 AFFINITY trial is projected to occur by the end of 2015, while the final analysis for the intent-to-treat population is projected to occur in the second half of 2016.

About the Phase 3 ENSPIRIT Trial
The Phase 3 ENSPIRIT trial is an international, randomized, open-label trial designed to evaluate custirsen for the treatment of advanced or metastatic NSCLC in 700 patients who have progressed after initial chemotherapy treatment, with a hypothesized hazard ratio (HR) of 0.75 and a critical HR of 0.84. The trial will investigate if combining custirsen with docetaxel, a standard second-line NSCLC chemotherapy, has the potential to improve survival outcomes compared to docetaxel alone in these patients. The trial is expected to enroll patients at approximately 50 sites globally. OncoGenex has filed an amendment with the FDA and regulatory agencies in all countries where it is the sponsor. The company will file in two remaining countries as it becomes the sponsor. For more information on the ENSPIRIT trial, please visit View Source

About Custirsen
Custirsen is an experimental drug that is designed to block the production of the protein clusterin, which may play a fundamental role in cancer cell survival and treatment resistance. Clusterin is upregulated in tumor cells in response to treatment interventions such as chemotherapy, hormone ablation and radiation therapy and has been found to be overexpressed in a number of cancers, including prostate, lung, breast and bladder. Increased clusterin production has been linked to faster rates of cancer progression, treatment resistance and shorter survival duration. By inhibiting clusterin, custirsen is designed to alter tumor dynamics, slowing tumor growth and resistance to partner treatments, so that the benefits of therapy, including survival, may be extended.

Custirsen has Fast Track designation by the U.S. Food and Drug Administration for NSCLC and metastatic CRPC.

CRT HIGHLIGHTED IN THE DOWLING REVIEW OF BUSINESS-UNIVERSITY RESEARCH COLLABORATIONS

On July 13, 2015 CRT reported it has been highlighted in the Dowling Review of Business-University Research Collaborations (Press release, Cancer Research Technology, JUL 13, 2015, View Source [SID1234523515]). The report states:

A good example [for TTOs] is provided by Cancer Research Technology (CRT), which works in partnership with Cancer Research UK to identify innovative scientific and business solutions to unmet needs in cancer, embodied in the vision ‘Advancing Discoveries to Beat Cancer’. CRT’s development and commercialisation activities are focused on driving delivery of the new Cancer Research UK research strategy, and this is also reflected in the metrics used to measure CRT’s performance. While CRT may not be a typical TTO, there is no reason why the principles underpinning its approach should not be more widely applicable. It is also worth noting that TTOs should measure their success over suitably long timescales: focusing on near-term results can drive behaviours that are counterproductive over the timescales that matter.