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Bayer Submits Marketing Authorization for Radium-223 Dichloride to Treat Prostate Cancer with Bone Metastases in Japan (for specialized target groups only)

On April 24, 2015 Bayer reported Bayer HealthCare has submitted an application for marketing authorization to the Ministry of Health, Labour and Welfare (MHLW) in Japan for radium-223 dichloride (radium-223) solution for injection for the treatment of prostate cancer patients with bone metastases (Press release, Bayer, APR 24, 2015, View Source [SID:1234503173]).

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"The number of patients suffering from prostate cancer has steadily increased in Japan over the past years, and for patients with advanced disease, there are limited options," said Dr. Joerg Moeller, Member of the Bayer HealthCare Executive Committee and Head of Global Development. "With its specific mode of action and the proven clinical benefit, radium-223 reflects our commitment to developing innovative cancer treatments for patients for whom only limited therapy options are available today."

The regulatory submission 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=0.695 (95% CI 0.552-0.875), p=0.00185]. Median OS was 14.0 months with radium-223 plus best standard of care vs. 11.2 months with placebo plus best standard of care. Additionally, at the interim analysis there was a delay in the time to first symptomatic skeletal event (SSE) for patients treated with radium-223 vs. placebo. An updated 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)].

The most common adverse reactions (occurring at a rate of 10% or greater) in patients receiving radium-223 in the ALSYMPCA trial were nausea, diarrhea, vomiting and peripheral edema. The most common hematologic laboratory abnormalities (occurring at a rate of 10% or greater) were anemia, lymphocytopenia, leukopenia, thrombocytopenia and neutropenia.

About the ALSYMPCA Trial
The ALSYMPCA trial was a Phase III, randomized, double-blind, placebo-controlled international study of radium-223 with best standard of care vs. placebo with best standard of care in symptomatic castration-resistant prostate cancer (CRPC) patients with bone metastases. The trial enrolled 921 patients in more than 100 centers in 19 countries. The study treatment consisted of up to six intravenous injections of radium-223 or placebo each separated by an interval of four weeks.

The primary endpoint of the study was OS. A key secondary endpoint was time to first SSE, as defined as external beam radiation therapy (EBRT) to relieve skeletal symptoms, new symptomatic pathologic bone fracture, occurrence of spinal cord compression or tumor-related orthopedic surgical intervention.

About Castration-Resistant Prostate Cancer (CRPC) and Bone Metastases
Prostate cancer is the second most commonly diagnosed malignancy in men worldwide. In 2012, an estimated 1,111,000 men were diagnosed with prostate cancer and 307,000 died from the disease worldwide. In Japan, an estimated 47,000 men were affected with prostate cancer and 12,000 died from the disease in 2013. 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.

CRPC is an advanced form of prostate cancer. A majority of men with CRPC have symptomatic bone metastases resulting in pain, skeletal events such as fractures or spinal cord compression, and/or reduced survival. In fact, bone metastases lead to an increased risk of morbidity and death in patients with CRPC.

About Radium-223 Dichloride
Radium-223 dichloride (radium-223) is a therapeutic alpha particle-emitting pharmaceutical with an anti-tumor effect on bone metastases. Radium-223 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.

Radium-223 has been approved under the brand name Xofigo in more than 40 countries worldwide, including the U.S. and the EU.

AstraZeneca enters strategic immuno-oncology collaboration with Celgene Corporation to develop PD-L1 inhibitor programme for patients with serious blood cancers

On April 24, 2015 AstraZeneca and MedImmune, the Company’s global biologics research and development arm, reported that they have entered into an exclusive collaboration agreement with Celgene Corporation, a global leader in hematological cancers, for the development and commercialisation of MEDI4736 across a range of blood cancers including non-Hodgkin’s lymphoma, myelodysplastic syndromes and multiple myeloma (Press release, AstraZeneca, APR 24, 2015, View Source;astrazeneca-enters-strategic-immuno-oncology-collaboration-Celgene-PD-L1-inhibitor-programme [SID:1234503171]).

MEDI4736 is an investigational immune checkpoint inhibitor, directed against programmed cell death ligand 1 (PD-L1). Signals from PD-L1 help tumours avoid detection by the immune system. MEDI4736 blocks these signals, countering the tumour’s immune-evading tactics. Within the collaboration, MEDI4736 will be assessed both as monotherapy and in combination with other AstraZeneca and Celgene potential and existing cancer medicines. Over time, the collaboration could expand to include other assets.

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Under the terms of the agreement, Celgene will make an upfront payment of $450 million to AstraZeneca in relation to MEDI4736. Celgene will lead on development across all clinical trials within the collaboration and will take on all research and development costs until the end of 2016, after which they will take on 75 percent of these costs. Celgene will also be responsible for global commercialisation of approved treatments. AstraZeneca will continue to manufacture and book all sales of MEDI4736 and will pay a royalty to Celgene on worldwide sales in haematological indications. The royalty rate will start at 70 percent and will decrease to approximately half of the sales of MEDI4736 in haematological indications over a period of four years.

Dr. Bahija Jallal, Executive Vice President at MedImmune, said: "We are excited about our strategic collaboration with Celgene, a globally recognised leader in treatments for haematological cancers. This agreement is a great example of how we are accelerating the development of medical innovation in our portfolio in collaboration with other experts, in order to bring life-enhancing new medicines to patients faster. Together with Celgene, we are designing a programme for our anti-PD-L1 that will explore its full potential as a game-changing treatment that could activate the patients’ immune system to fight and change the course of blood cancers in this area of high unmet need."

"The potential of rationally combining immunotherapies such as MEDI4736 with existing and novel haematology compounds creates new opportunities for patients with blood cancers to live longer, better lives," said Jacqualyn A. Fouse, Ph.D., President, Global Haematology and Oncology for Celgene. "This strategic collaboration leverages the deep expertise of AstraZeneca/MedImmune in immuno-oncology along with the experience of Celgene in the study and treatment of blood cancers. This collaboration advances Celgene’s already deep, diverse scientific platform to include checkpoint inhibitors, an area of significant promise in haematology."

The collaboration agreement will become effective upon the expiration or termination of applicable waiting periods under all applicable antitrust laws, if any, and is expected to become effective in the second quarter of 2015. AstraZeneca’s 2015 financial guidance is unaffected by today’s announcement.

NOTES TO EDITORS

About MEDI4736

MEDI4736 is an investigational human monoclonal antibody directed against programmed cell death ligand 1 (PD-L1). Signals from PD-L1 help tumours avoid detection by the immune system. MEDI4736 blocks these signals, countering the tumour’s immune-evading tactics.

MEDI4736 was accelerated into Phase III clinical development in non-small cell lung cancer and head and neck cancer. The OCEANS clinical development programme will evaluate MEDI4736 as monotherapy and in combination with a CTLA-4 (tremelimumab) in lung cancer, across the spectrum of the disease. In head and neck cancer, MEDI4736 is being investigated both as monotherapy and in combination with tremelimumab, looking at patients with different PD-L1 expression status who have failed on chemotherapy.

AstraZeneca and Innate Pharma announce global co-development and commercialisation collaboration for IPH2201 in immuno-oncology

On April 24, 2015 AstraZeneca and MedImmune, the Company’s global biologics research and development arm, reported that they have entered into a collaboration to accelerate and broaden the development of Innate Pharma SA’s proprietary anti-NKG2A antibody, IPH2201, including in combination with MEDI4736, an anti-PD-L1 immune checkpoint inhibitor developed by MedImmune (Press release, AstraZeneca, APR 24, 2015, View Source;astrazeneca-and-innate-pharma-announce-global-co-development-and-commercialisation-collaboration-IPH2201 [SID:1234503170]). Currently in Phase II development, IPH2201 is a potential first-in-class humanised IgG4 antibody. NKG2A is a checkpoint receptor that inhibits the anti-cancer functions of Natural Killer (NK) and cytotoxic T-cells.

The initial development plan includes: Phase II combination clinical trials with MEDI4736 in solid tumours; multiple Phase II trials planned by Innate to study IPH2201 both as monotherapy and in combination with currently approved treatments across a range of cancers; and the development of associated biomarkers.

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The combination of IPH2201 with MEDI4736 adds to the broad programme of immuno-oncology combination trials that AstraZeneca and MedImmune have planned and underway. The studies aim to address multiple immune pathways, harnessing AstraZeneca’s own extensive pipeline and working in partnership to explore the significant potential of immunotherapies in transforming the way cancer patients are treated.

Under the terms of the agreements, AstraZeneca will make an initial payment to Innate of $250 million, which includes the consideration for exclusive global rights to co-develop and commercialise IPH2201 in combination with MEDI4736, as well as access to IPH2201 in monotherapy and other combinations in certain treatment areas. AstraZeneca will pay a further $100 million prior to initiation of Phase III development, as well as additional regulatory and sales-related milestones. AstraZeneca will book all sales and will pay Innate double-digit royalties on net sales. The arrangement includes the right for Innate to co-promote in Europe for a 50% profit share in the territory.

Pascal Soriot, Chief Executive Officer of AstraZeneca, said: "We are pleased to collaborate with Innate Pharma to bring this prospective first-in-class treatment to cancer patients, further strengthening our broad immuno-oncology pipeline. We believe that combination therapy in immuno-oncology has the potential to be one of the most effective ways of treating cancer and that by targeting both innate and acquired immunity we have the opportunity to deliver important clinical benefit to patients across a range of cancers."

Hervé Brailly, CEO and co-founder of Innate Pharma, said: "This agreement allows Innate Pharma to broaden and accelerate the development of anti-NKG2A while preserving our innovative development plan. It provides Innate Pharma with the capabilities and resources to transform the company towards late stage development and potential commercial stage with co-promotion rights. We look forward to partnering with AstraZeneca and MedImmune, leaders in immuno–oncology, in this transforming transaction for Innate Pharma."

The transaction is subject to customary terms and conditions, including the expiration or termination of the waiting period under the Hart-Scott-Rodino Antitrust Improvements Act, and is expected to become effective in the second quarter of 2015. AstraZeneca’s 2015 financial guidance is unaffected by today’s announcement.

NOTES TO EDITORS

About Innate Pharma’s anti-NKG2A

IPH2201 is a first-in-class immune checkpoint inhibitor targeting NKG2A receptors expressed on tumor infiltrating cytotoxic NK and CD8 T lymphocytes.

NKG2A is an inhibitory receptor binding HLA-E. By expressing HLA-E, cancer cells can protect themselves from killing by NKG2A+ immune cells. HLA-E is frequently up-regulated on cancer cells of many solid tumors or hematological malignancies. IPH2201, a humanized IgG4, blocks the binding of NKG2A to HLA-E allowing activation of NK and cytotoxic T cell responses. Hence, IPH2201 may re-establish a broad anti-tumor response mediated by NK and T cells. IPH2201 may also enhance the cytotoxic potential of other therapeutic antibodies.

About MEDI4736

MEDI4736 is an investigational human monoclonal antibody directed against programmed cell death ligand 1 (PD-L1). Signals from PD-L1 help tumours avoid detection by the immune system. MEDI4736 blocks these signals, countering the tumour’s immune-evading tactics.

MEDI4736 was accelerated into Phase III clinical development in non-small cell lung cancer and head and neck cancer. The OCEANS clinical development programme will evaluate MEDI4736 as monotherapy and in combination with a CTLA-4 (tremelimumab) in lung cancer, across the spectrum of the disease. In head and neck cancer, MEDI4736 is being investigated both as monotherapy and in combination with tremelimumab, looking at patients with different PD-L1 expression status who have failed on chemotherapy.

Novartis Q1 Results 2015

On April 23, 2015 Commenting on the results, Joseph Jimenez, CEO of Novartis, reported: "Our focus on execution has resulted in a strong operational performance (Press release, Sandoz, APR 23, 2015, View Source [SID:1234506744]). We have completed the GSK and Lilly transactions and innovation continues to be strong. We had three approvals in Oncology, FDA priority review for LCZ696, Zarxio became the first biosimilar approved under the new pathway in the US and we launched Cosentyx globally. We are on track to deliver our full-year guidance."

Continuing operations1 saw sales, core2 operating income and core EPS grow (cc2) in Q1
Net sales were USD 11.9 billion (-7%, +3% cc)2
Operating income was USD 2.8 billion (-1%, +15% cc)
Core operating income (-4%, +9% cc) grew faster than sales (cc), resulting in core margin of 30.6%
Core EPS was USD 1.33 (-1%, +11% cc))
Further strengthening of USD impacted sales by -10% and core operating income by -13%
Free cash flow2 increased 27% to USD 1.5 billion

For total Group, Q1 divestments resulted in exceptional operating income gains totaling USD 12.8 billion and net income gains of USD 10.8 billion

Strong progress on innovation continued in Q1
Three approvals in Oncology: Jakavi in polycythemia vera (EU), Farydak in multiple myeloma (US) and Jadenu for chronic iron overload (US)

LCZ696 granted FDA priority review and CHMP accelerated assessment in heart failure
Positive trials on Cosentyx in psoriasis showing superiority to Stelara, sustained two-year efficacy
Sandoz received FDA approval for first biosimilar Zarxio and in April for first substitutable generic version of Copaxone 20mg one-time-daily injection, Glatopa

Growth Products3 and Emerging Growth Markets3 continued to drive performance in Q4
Growth Products grew 14% (USD) to USD 4.7 billion, or 32% of Group net sales
Strong performance in Emerging Growth Markets (+12% cc)

Portfolio rejuvenation continued in Q1, reinforcing growth prospects for continuing operations
Growth Products3 grew 15% (USD) to USD 3.7 billion, or 31% of net sales
Strong performance in Emerging Growth Markets3 (+12% cc)

Continued progress in transforming portfolio and increasing productivity
Transactions with GSK and Lilly closed on March 2 and January 1, respectively; divestment of influenza Vaccines business to CSL expected to be completed in H2 2015
For continuing operations, core margin improved (+1.7 percentage points cc) mainly due to ongoing productivity initiatives

Outlook 2015 for continuing operations confirmed
Net sales expected to grow mid-single digit (cc); core operating income expected to grow ahead of sales at a high-single digit rate (cc) (cc)

MedImmune and Juno Therapeutics Announce Immuno-Oncology Clinical Trial Collaboration

On April 23, 2015 MedImmune and Juno reported that they have entered into a new collaboration to conduct combination clinical trials in immuno-oncology with one of Juno’s investigational CD19-directed chimeric antigen receptor (CAR) T cell candidates and MedImmune’s investigational programmed cell death ligand 1 (PD-L1) immune checkpoint inhibitor, MEDI4736 (Press release, Juno, APR 23, 2015, View Source [SID:1234503138]). Under the initial development plan, both companies will explore the safety, tolerability and preliminary efficacy of the combination therapy as a potential treatment for patients with non-Hodgkin lymphoma (NHL).

"We are pleased to enter into this clinical trial collaboration with Juno Therapeutics as our initial venture into the promising emerging field of CAR T cell therapies," said Dr. Ed Bradley, Senior Vice President and Head of the Oncology Innovative Medicines unit, MedImmune. "The combination of Juno’s CAR T cell candidate with MEDI4736 adds to our broad program of immuno-oncology combination trials, addressing multiple immune pathways and working with industry-leading partners to explore the significant potential of immunotherapies in transforming treatments for cancer."

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Under the terms of the non-exclusive collaboration, MedImmune and Juno will jointly co-fund the initial Phase Ib study, which is expected to begin later in 2015. The companies will also explore the combination of MEDI4736 with a next-generation, Juno-developed fully human CD19-directed CAR T cell candidate.

"We believe combination strategies such as this will help us better understand the full potential of our engineered T cell platform in both hematological and solid tumor settings," said Mark W. Frohlich, M.D., Executive Vice President, Research & Development at Juno Therapeutics. "We look forward to working with MedImmune, a leader in immuno-oncology and checkpoint inhibition, in understanding the potential clinical benefit of combining these two potent therapeutic classes."

Financial details were not disclosed.

About MEDI4736
MEDI4736 is an investigational human monoclonal antibody directed against programmed cell death ligand 1 (PD-L1). Signals from PD-L1 help tumours avoid detection by the immune system. MEDI4736 blocks these signals, countering the tumour’s immune-evading tactics.
MEDI4736 was accelerated into Phase III clinical development in non-small cell lung cancer and head and neck cancer. The OCEANS clinical development programme will evaluate MEDI4736 as monotherapy and in combination with a CTLA-4 (tremelimumab) in lung cancer, across the spectrum of the disease. In head and neck cancer, MEDI4736 is being investigated both as monotherapy and in combination with tremelimumab, looking at patients with different PD-L1 expression status who have failed on chemotherapy.
About Chimeric Antigen Receptor (CAR) Technology
Juno’s chimeric antigen receptor (CAR) technology genetically engineers T cells to recognize and kill cancer cells. Juno’s CAR T cell technology inserts a gene for a particular CAR into the T cell, enabling it to recognize cancer cells based on the expression of a specific protein located on the cell surface. When the engineered T cell engages the target protein on the cancer cell, it initiates a cell-killing response against the cancer cell.