Roche provides update on phase III study of onartuzumab in people with specific type of lung cancer

Roche  announced  that an independent data monitoring committee has recommended that the phase III METLung study be stopped due to a lack of clinically meaningful efficacy.

The study evaluated if onartuzumab (MetMab) in combination with Tarceva (erlotinib) helped patients with previously treated, advanced non-small cell lung cancer (NSCLC) whose tumours were identified as MET-positive live longer compared to Tarceva alone. Overall adverse event rates were generally similar between the two groups. Data will be submitted for presentation at a forthcoming medical meeting.

« These results are disappointing because new options are needed for patients with lung cancer, the most common and deadly cancer worldwide,” said Sandra Horning, M.D., Chief Medical Officer and Head of Global Product Development. « We remain committed to helping patients with lung cancer and are studying several investigational medicines in this disease.”

Roche is evaluating the implications of the METLung study results across the ongoing onartuzumab clinical programme.

About the METLung Study (NCT01456325)

  • METLung is a Phase III, randomised, double-blind study evaluating the efficacy and safety profile of onartuzumab in combination with Tarceva in patients with previously treated (second- or third-line) advanced NSCLC identified to be MET-positive. The METLung study included a companion diagnostic immunohistochemistry (IHC) test that was co-developed with Ventana Medical Systems, Inc., a member of the Roche Group.
  • Four hundred and ninety-nine patients were randomized to receive 150 mg of Tarceva taken daily plus either:
    • Intravenous 15 mg/kg of onartuzumab every three weeks
    • Intravenous placebo every three weeks
  • The primary endpoint is overall survival. Secondary endpoints include progression-free survival, objective response rate and safety profile.
  • The results announced today are from a pre-specified interim analysis.

About Lung Cancer

According to the World Health Organization, it is estimated that nearly 1.6 million people worldwide died of lung cancer in 2012; NSCLC accounts for 85 percent of all lung cancers.

About the MET Pathway

MET is a protein found on the surface of cells and acts as a receptor that binds to another protein called Hepatocyte Growth Factor (HGF), also known as « Scatter Factor ». When HGF binds to MET, it causes MET proteins to form pairs (dimerise), which triggers a signalling cascade that tells cells to grow, divide, and spread to other parts of the body. Activation of the MET pathway has been proposed as a mechanism of tumour growth and spread (metastasis).

About Onartuzumab

Onartuzumab, an investigational monovalent (one-armed) monoclonal antibody designed to specifically target the MET receptor, is being studied in various cancers.

 

Source: Roche

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New Marketing Authorisation Application Submitted to EMA for Ibrutinib for the Treatment of Two Forms of Blood Cancer

The submission is for chronic lymphocytic leukemia (CLL)/small lymphocytic leukemia (SLL) and mantle cell lymphoma (MCL), two difficult-to-treat diseases

 

Janssen-Cilag International NV (Janssen) announced today it has submitted a Marketing Authorization Application (MAA) to the European Medicines Agency (EMA) for ibrutinib for the treatment of adult patients with relapsed or refractory chronic lymphocytic leukemia (CLL)/small lymphocytic leukemia (SLL) or relapsed or refractory mantle cell lymphoma (MCL), two forms of blood cancer.

Ibrutinib is administered orally, once-daily and is the first in a class of medicines called Bruton’s tyrosine kinase (BTK) inhibitors. Data suggest ibrutinib covalently bonds to BTK in malignant B cells, shutting down major proliferation and survival pathways. Ibrutinib is being developed by Janssen with Pharmacyclics, Inc. for the treatment of several forms of blood cancer. If approved, ibrutinib will be the first commercially available therapy targeting BTK.

« The EMA Marketing Authorisation Application is an important milestone in the development of ibrutinib, » said Jane Griffiths, Group Company Chairman of Janssen Europe, the Middle East and Africa (EMEA). « At Janssen, we are dedicated to developing solutions that prolong and improve the lives of patients. If approved, ibrutinib will address a great unmet need for patients with CLL/SLL and MCL who have previously failed or become resistant to previous treatment. »

The EMA filings follow the New Drug Application submission of ibrutinib to the U.S. Food and Drug Administration which was announced on 10 July 2013, for its use in the treatment of previously treated patients with CLL/SLL or MCL.

CLL/SLL and MCL belong to a group of blood cancers, known as B-cell malignancies, originating from B cells, a type of white blood cell (lymphocyte).(1)CLL/SLL and MCL, are complex diseases that can be challenging to treat. As a result, many patients will relapse after a specific treatment and may require multiple treatments over the course of their disease.

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About Ibrutinib

Ibrutinib is the first in a class of medicines called Bruton’s tyrosine kinase (BTK) inhibitors. BTK is an important protein involved in mediating the cellular signaling pathways which control B cell maturation and survival. In malignant B cells, there is excessive signaling through the B cell receptor signaling (BCR) pathway, which includes BTK. The malignant cell ignores the natural signal to die and continues to develop and proliferate. Malignant cells migrate and adhere to protective environmental areas such as the lymph nodes where they proliferate and survive. Ibrutinib is the first in a new class of drugs specifically designed to target and inhibit BTK. Ibrutinib forms a strong covalent bond with BTK, which inhibits the excessive transmission of cell survival signals within the malignant B cells and stops their excessive build up in these protected environmental areas. The efficacy and safety of ibrutinib alone and in combination with other treatments is being studied in several blood cancers.(2,3,4,5,6)

About Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Leukemia (SLL)

CLL is a usually slow growing blood cancer that most commonly originates from B cells, a type of white blood cell (lymphocyte) that develops in the bone marrow. B cells are part of the immune system and play an important role in fighting infection in the body. CLL is the most common adult leukemia in the Western world, with the median age at diagnosis being primarily those over 70 years old. The incidence rates among men and women in Europe are approximately 5.87 and 4.01 cases per 100,000 persons per year, respectively. CLL is a chronic disease; median overall survival ranges between 18 months and more than 10 years according to the stage of disease. When cancer cells are located mostly in the lymph nodes, the disease is called small lymphocytic lymphoma (SLL).(7,8,9,10,11,12)

About Mantle Cell Lymphoma (MCL)

MCL is a rare and aggressive blood cancer that usually occurs in older adults, with the median age at diagnosis being 65 years. The disease typically begins in the bone marrow, but can spread to other tissues such as bone marrow, liver and spleen. The incidence rates among men and women in Europe are approximately 0.64 and 0.27 cases per 100,000 persons per year, respectively. MCL patients generally have a poor prognosis. Median overall survival is typically three to four years, and only one to two years in patients following the first relapse. (13,14,15,16)

About Janssen

The Janssen Pharmaceutical Companies of Johnson & Johnson are dedicated to addressing and solving the most important unmet medical needs of our time, including oncology, immunology, neuroscience, infectious disease, and cardiovascular and metabolic diseases. Driven by our commitment to patients, Janssen develops innovative products, services and healthcare solutions to help people throughout the world. More information can be found at http://www.janssen-emea.com

Janssen in Oncology

In oncology, our goal is to fundamentally alter the way cancer is understood, diagnosed, and managed, reinforcing our commitment to the patients who inspire us. In looking to find innovative ways to address the cancer challenge, our primary efforts focus on several treatment and prevention solutions. These include a focus on hematologic malignancies, prostate cancer and lung cancer; cancer interception with the goal of developing products that interrupt the carcinogenic process; biomarkers that may help guide targeted, individualized use of our therapies; as well as safe and effective identification and treatment of early changes in the tumor microenvironment.

Janssen and Pharmacyclics Strategic Partnership

Ibrutinib is being co-developed as part of a strategic partnership between Janssen and Pharmacyclics, Inc. Both companies are responsible for the development, manufacturing and commercialisation of ibrutinib. In Europe, Janssen is the lead party for the commercialisation of ibrutinib, if approved. Details about the complete ibrutinib clinical program are posted on clinicaltrials.gov.

(This press release contains « forward-looking statements » as defined in the Private Securities Litigation Reform Act of 1995. The reader is cautioned not to rely on these forward-looking statements. These statements are based on current expectations of future events. If underlying assumptions prove inaccurate or unknown risks or uncertainties materialize, actual results could vary materially from the expectations and projections of Janssen-Cilag International NV, any of the other Janssen Pharmaceutical Companies and/or Johnson & Johnson. Risks and uncertainties include, but are not limited to, general industry conditions and competition; economic factors, such as interest rate and currency exchange rate fluctuations; technological advances, new products and patents attained by competitors; challenges inherent in new product development, including obtaining regulatory approvals; challenges to patents; changes in behavior and spending patterns or financial distress of purchasers of health care products and services; changes to governmental laws and regulations and domestic and foreign health care reforms; trends toward health care cost containment; and increased scrutiny of the health care industry by government agencies. A further list and description of these risks, uncertainties and other factors can be found in Exhibit 99 of Johnson & Johnson’s Annual Report on Form 10-K for the fiscal year ended December 30, 2012. Copies of this Form 10-K, as well as subsequent filings, are available online at http://www.sec.gov, http://www.jnj.com or on request from Johnson & Johnson. None of the Janssen Pharmaceutical Companies nor Johnson & Johnson undertake to update any forward-looking statements as a result of new information or future events or developments.)

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References

1. National Cancer Institute. Definition: B cell. Available from: http://www.cancer.gov/dictionary?cdrid=45611. Accessed May 14, 2013.

2. Qiu Y, Kung HJ. Signaling network of the Btk family kinases. Oncogene 2000;19:5651-61.

3. Shaffer AL, Rosenwald A, Staudt LM. Lymphoid malignancies: the dark side of B-cell differentiation. Nat Rev Immunol. 2002;2:920-32.

4. Puri KD, di Paolo JA, Gold MR. B-cell receptor signaling inhibitors for treatment of autoimmune inflammatory diseases and B-cell malignancies. Int Rev Immunol 2013;32:397-427.

5. Woyach JA, Johnson AJ, Byrd JC. The B-cell receptor signaling pathway as a therapeutic target in CLL. Blood 2012;120:1175-84.

6. Akinleye A, Chen Y, Mukhi N, Song Y, Liu D. Ibrutinib and novel BTK inhibitors in clinical development. J Hematol Oncol 2013;6:59.

7. Parker, T. Chronic lymphocytic leukemia: prognostic factors and impact on treatment. Discovery Medicine. 2011; 57.

8. SEER Statistics. Fact Sheets: Chronic lymphocytic leukemia. Available from: http://seer.cancer.gov/statfacts/html/clyl.html. Accessed March 6, 2013.

9. American Cancer Society. Detailed guide: what is chronic lymphocytic leukemia. Available from: http://www.cancer.org/cancer/leukemia-chroniclymphocyticcll/detailedguide/leukemia-chronic-lymphocytic-what-is-cll. Accessed March 6, 2013.

10. Sant M, Allemani C, Tereanu C, et al. Incidence of hematologic malignancies in Europe by morphologic subtype: results of the HAEMACARE project. Blood 2010;116:3724-34.

11. Cancer Research UK. The most common types of non-Hodgkins lymphoma. Available from: http://www.cancerresearchuk.org/cancerhelp/type/non-hodgkins-lymphoma/about/types/the-most-common-types-of-non-hodgkins-lymphoma#sll. Accessed March 14, 2013.

12. Sagatys EM, Zhang L. Clinical and laboratory prognostic indicators in chronic lymphocytic leukemia. Cancer Control 2012;19:18-25.

13. McKay P, Leach M, Jackson R, et al. Guidelines for the investigation and management of mantle cell lymphoma. Br J Haematol 2012;159:405-26.

14. Leukemia and Lymphoma Society. Mantle Cell Lymphoma Facts. Available from: http://www.lls.org/content/nationalcontent/resourcecenter/freeeducationmaterials/lymphoma/pdf/mantlecelllymphoma.pdf. Accessed May 14, 2013.

15. Smedby KE, Hjalgrim H. Epidemiology and etiology of mantle cell lymphoma and other non-Hodgkin lymphoma subtypes. Semin Cancer Biol 2011;21:293-8.

16. Goy A, Bernstein SH, Kahl BS, et al. Bortezomib in patients with relapsed or refractory mantle cell lymphoma: updated time-to-event analyses of the multicenter phase 2 PINNACLE study. Ann Oncol 2009;20:520-5.

SOURCE: Jansse

Roche’s obinutuzumab (GA101) delayed disease progression longer than MabThera/Rituxan in people with one of the most common forms of blood cancer

  • Phase III CLL11 study showed GA101 plus chlorambucil, a chemotherapy, was superior to MabThera/Rituxan plus chlorambucil in helping people with previously untreated chronic lymphocytic leukemia live longer without their disease worsening
  • Final data from the CLL11 study will be submitted to the American Society of Hematology’s 55th Annual Meeting in December 2013

Roche  announced positive results from the phase III CLL11 study. At a pre-planned interim analysis, an independent data monitoring committee determined that the study met its primary endpoint showing that GA101 plus chlorambucil helped people live significantly longer without their disease worsening (progression-free survival; PFS) compared to MabThera/Rituxan plus chlorambucil. The CLL11 study is being conducted in cooperation with the German CLL Study Group (GCLLSG). These final data were reached well ahead of the target completion date in 2014 as a result of the magnitude of difference seen between the two study arms. No new safety signals for GA101 or MabThera/Rituxan were identified in this analysis, and adverse events were similar to those observed in the first stage of the study which was previously reported earlier this year.

“The positive final results from the CLL11 study show the promise that GA101 could hold for people with CLL,” said Hal Barron, M.D., Roche’s Chief Medical Officer and Head, Global Product Development. « It is important to explore the potential of this medicine in other types of blood cancer, and our broad development program includes studies in aggressive and indolent lymphoma that compare GA101with MabThera/Rituxan. »

GA101 is the first type II anti-CD20 medicine that is glycoengineered, which means specific sugar molecules in GA101 were modified to change its interaction with the body’s immune cells.

This modification creates a unique antibody that is designed to act as an immunotherapy, engaging the patient’s own immune system to help attack the cancerous cells; in addition, GA101 binds to CD20 with the aim of inducing direct cell death.

These data will be submitted for consideration to the 55th Annual Meeting of the American Society of Hematology (ASH) in New Orleans, which is taking place December 7-10, 2013.

Based on an earlier analysis (stage 1) of the CLL11 study, marketing applications for GA101 were submitted to regulatory authorities including the U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA) in April, 2013. Due to the significance of the positive trial results and the serious and life threatening nature of CLL, the FDA granted the GA101 application both Breakthrough Therapy Designation and Priority Review.

 

Source : Roche

Erytech Announces Fast-Off of its Phase IIB Study in Acute Myeloid Leukemia

The study, a multicentre, open, randomized, controlled Phase IIb trial evaluating efficacy and tolerability of GRASPA® in the treatment of newly diagnosed acute myeloid leukemia (AML) patients, over 65 years, unfit for intensive chemotherapy, was initiated in March 2013.

In the mean time and in line with the planning, all 21 French investigation sites have been authorized to participate in the study. With 13 of these sites having been initiated and opened so far, already 12 out of a total of 123 patients have been enrolled in the study. The current pace of inclusion shall enable ERYTECH to recruit the last patient in the study before the end of 2014. In parallel to the patient recruitments realized in France, it is foreseen to open other specialized centers in different European countries in view of internationalizing the study and further accelerating patient enrollment.

The study is performed in collaboration with Orphan Europe (Recordati Group), ERYTECH’s partner for the commercialization of GRASPA® in 38 pays European countries, under a licensing and distribution agreement that was signed at the end of 2012.

In February 2013, the European Medicines Agency (EMA) granted GRASPA® the orphan drug status for the treatment of AML. The orphan drug status provides certain advantages for the sponsor such as reduced procedure costs and ten years of commercial exclusivity.

With about 34 000 new patients per year in Europe and the US, AML is the most common type of acute leukemia. Affecting mainly the adult and senior patient population that often cannot tolerate the existing forms of asparaginase products, AML represents one of the highest mortality rates among all type of cancers and an important unmet medical need.

To address this challenge, ERYTECH can build on its solid experience in Acute Lymphoblastic Leukemia (ALL) where GRASPA®, currently in Phase III of clinical development, has already demonstrated convincing clinical results both in terms of safety and efficacy in fragile adult and senior patients. In ALL, GRASPA® benefits from the orphan drug status both in Europe and in the US.

« We are very pleased with the fast take-off of this study and by the adoption of GRASPA® by the clinicians, confirming their need for new therapies enabling them to treat adult and senior acute leukemia patients efficiently. The increased tolerability profile obtained through the encapsulation of asparaginase in the red blood cells opens perspectives to treat all patients suffering from acute leukemia, even the most fragile ones, not only the children. » comments Yann Godfrin, co-founder and CSO of ERYTECH.

« Much in line with this Phase IIb study in which patient recruitment is happening at a fast pace, we are pursuing the execution of our clinical development plan we announced during our initial public offering in April. The next steps will concern our studies in ALL in Europe and the US, as well as in solid tumors. » concludes Gil Beyen, Chairman and CEO of ERYTECH.

 

Source: Erytech