Blinatumomab will change the future of relapsed/refractory Acute Lymphoblastic Leukemia patients?

During the ASCO 2014, Amgen had shown the latest data of a novel ALL treatment, Blinatumomab.

Blinatumomab, a bispecific single-chain antibody targeting the CD19 antigen, is a member of a novel class of antibodies that redirect T cells for selective lysis of tumor cells. Blinatumomab is currently investigated for acute lymphoblastic leukemia (ALL), specially in persistence or relapse/ refractory after chemotherapy indicates resistance to chemotherapy. As the current ALL treatment were knowing for the high toxicity and low medical response, Blinatumomab can offer a real medical alternative.  Blinatumomab, was designed as orphan drug by the FDA for ALL in 2008. Blinatumomab binds to CD19, a protein which is expressed solely by B cells and is overexpressed in ALL tumor cells. Blinatumomab also binds to cytotoxic T cells through an interaction with the protein CD3, redirecting T cells to lyse CD19-expressing B-precursor ALL cells. The Phase II study of blinatumomab, reflect the potential of this molecule as an first-in-class bispecific T cell antibody.

The results showed that 43% of the 189 blinatumomab-treated patients achieved complete remission (CR) or CR with partial hematological recovery (CRh) within the first two cycles of therapy, with 80% of responses occurring within the first cycle. The median relapse-free survival was 5.9 months, and OS was 6.1 months. In total, patients were treated with more than five cycles of blinatumomab.

In cycle 1, patients underwent a run-in phase of 9μg blinatumomab per day for the first week, with 28μg per day for the remaining three weeks.

In cycle 2, patients were treated with 28μg blinatumomab per day.

The primary endpoint assessment of CR/CRh was performed at the end of the second cycle, and patients who responded to blinatumomab therapy were eligible to receive three additional cycles of therapy.

Current acute lymphoblastic leukemia chemotherapies were mainly composed by four-drug combination of vincristine, prednisone, anthracycline, and cyclophosphamide or L-asparaginase, or a five-drug combination including vincristine, prednisone, anthracycline, cyclophosphamide, and L-asparaginase. Although, the treatment related high mortality rate around 20 to 30%. Otherwise, there is an important unmet need for innovative therapies, more safe and efficient for the patient.

If Blinatumomab will demonstrate efficacy and safety in ALL treatment, the new compound will have the chance to reach a high pricing regarding the FDA orphan drug accreditation. Blinatumomab is currently investigated in the Phase III TOWER trial versus the investigator’s choice of standard of care chemotherapy in adult subjects with R/R precursor B-cell ALL.

Regarding the blinatumomab’s result shown in ASCO convincing results in adult patients with R/R ALL, and the important medical need, blinatumomab seems to be a possible multi-indication revolution for ALL, and non-Hodgkin’s lymphoma patients.

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Gustave Roussy Announces Oncology Joint Strategic Research Alliance With AstraZeneca

Villejuif, France, 5 June 2014 – Gustave Roussy Comprehensive Cancer Center and AstraZeneca have entered into a joint strategic alliance focussed on early oncology drug development. Gustave Roussy and AstraZeneca will develop a joint Strategic Collaboration Plan that will be overseen by a Joint Steering Committee.

As part of this strategic alliance, AstraZeneca will make its entire portfolio of innovative oncology molecules for pre-clinical, translational and early clinical studies available to Gustave Roussy, with the goal of targeting molecular aberrations that drive individual cancers via the modulation of critical cellular signalling pathways and deepening our understanding of how the patient’s immune system interacts with cancer

The Alliance will involve several parallel and inter-connected projects that will span preclinical, translational and clinical phases of drug development.

“Over the last 5 years, AstraZeneca has entrusted Gustave Roussy with a growing number of phase I trials. Through this alliance we hope to strengthen such an interaction and accelerate access to innovative therapies for all our patients“ – say Pr Alexander Eggermont (General Director of Gustave Roussy, Comprehensive Cancer Center) and Pr Jean-Charles Soria (Chairman Drug Development Department, DITEP, at Gustave Roussy).

Susan Galbraith, Head of the Oncology Innovative Medicines Unit at AstraZeneca, commented: “I am delighted to formalise and expand our longstanding relationship with Gustave Roussy.  AstraZeneca has over 40 years’ experience in developing cancer drugs, pushing the boundaries of science to improve survival rates for patients around the world.  Gustave Roussy’s integrated, innovative approach to cancer research is renowned.  I hope very much that we will continue to build on this alliance to accelerate drug discovery and   ultimately get drugs to the patients who need them.”

Antoine Yver, Head of Oncology, AstraZeneca’s global medicines development unit added, “We have a number of pre-clinical and clinical projects already underway with Gustave Roussy. The signing of this alliance allows us to continue our endeavours led by three new steering groups which will determine strategy and drive individual projects within the pre-clinical and clinical arena.”

Françoise Bartoli, AstraZeneca France Company President said:  “With this Alliance, AstraZeneca reinforces its partnership in France with oncology academia and public research and its collaboration with Gustave Roussy’s highly experienced and talented teams.” 

 

Source: IGR

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

Zaltrap,is the new mCRC Sanofi’s blockbuster ?

From a long time Sanofi is a major company in oncology with various blockbuster Taxotere (docetaxel / Sanofi ) or Eloxatin (oxaliplatin/ Sanofi) are manly considered as  standard. In metastatic colorectal cancer they are a multiple chemotherapy regimens were Sanofi are already an important actor, otherwise with the patent cliff is clear that Sanofi have to find new product in order to keep a leading position within the oncology market. The success of Avastin in the mCRC has generated an interest in angiogenesis inhibitors for CRC. As a result, there is a high level of competition between new anti-angiogenesis agents in the CRC pipeline.

Saying this, Zaltrap (aflibercept; Regeneron/Sanofi) is the first targeted therapy launched by Sanofi. The positive result of Phase III VELOUR is an evidence of the potential Zaltrap success. Zaltrap is a human recombinant protein composed by segments of the human vascular endothelial growth factor receptors 1 and 2 (VEGFR1/2) and portion of human immunoglobulin G1 (IgG1)

The design of the VELOUR Phase III trial show that Zaltrap was being developed for use in the second-line metastatic colorectal cancer (mCRC) after Avastin  in the first-line setting. Sanofi is investigating the indication for naïve patient didn’t be treated by Avastin. Obviously Zaltrap have to differentiate from Avastin in order to face future competitors such as brivanib (BMS)

Zaltrap received in august 2012 an FDA approval for use in combination with FOLFIRI (fluorouracil, leucovorin, and irinotecan) to treat patients with metastatic colorectal cancer (mCRC) that are resistant to or have progressed following an oxaliplatin-containing regimen. In Europe Zaltrap received this marketing authorization from the EMA in February 2013.

Zaltrap is positioned in the second line mCRC treatment when Avastin fails or as an alternative in indications where Avastin is not approved, in order to avoid a direct competition with Avastin.

 

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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

Roche launches new ProGRP test for more precise diagnosis in lung cancer

Roche announced the global launch (except US) of Elecsys ProGRP, a test that distinguishes between the two main types of lung cancer – small cell (SCLC) and non-small cell (NSCLC) lung cancer – and can help diagnose early-stage SCLC. Correct differential diagnosis in lung cancer is important, as the two types have different prognoses and must be treated differently: early-stage NSCLC can be cured by surgery, while SCLC is treated with chemo- and radiotherapy. Studies have shown that ProGRP as a standalone test is superior to the current standard neuron-specific enolase (NSE)1) test and that measuring both ProGRP and NSE enhances diagnostic accuracy.

The ProGRP test from Roche is the first which can be determined in serum or plasma. This allows a combined application with NSE from a single sample tube. Healthcare professionals benefit from ProGRP by improved determination of the histological subtype if biopsy results are unclear.

“As a leader in oncology, Roche is committed to providing reliable diagnostic tests to enable earlier detection of cancer,” said Roland Diggelmann, COO Division Roche Diagnostics. “Until now, patients with SCLC have usually been diagnosed only when the disease has reached an advanced stage, when the chances of a cure are very low. ProGRP meets a medical need for more precise diagnosis, supporting medical decision making and helping healthcare professionals to improve patient outcomes.”

Lung cancer is one of the most common cancers worldwide. Approximately 1.35 million new cases are diagnosed every year, representing almost 13% of all new cancer diagnoses. Smoking is the main risk factor. Small cell lung cancer (SCLC) is particularly aggressive, spreading rapidly to lymph nodes and other organs.

 

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