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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NICE requests more data on bortezomib for multiple myeloma

NICE requests more data on bortezomib for multiple myeloma

In draft guidance, published today (12 November), NICE has asked Janssen to provide more data on the effectiveness of their product, bortezomib (Velcade) as a treatment for some patients with newly diagnosed multiple myeloma.
This appraisal is examining the use of bortezomib for treating multiple myeloma in combination with dexamethasone and thalidomide. The draft guidance has been issued for consultation and the manufacturer now has an opportunity to respond to the independent Appraisal Committee’s considerations and requests.
NICE has requested further evidence on the clinical and cost effectiveness of bortezomib in combination with dexamethasone compared with current standard treatment of newly diagnosed patients who are suitable for high dose chemotherapy with haematopoietic stem cell transplantation. Standard treatment in the UK is a combination of cyclophosphamide, thalidomide and dexamethasone.
The draft guidance does not currently recommend bortezomib in combination with thalidomide and dexamethasone.
Dr Carole Longson, Health Technology Evaluation Centre Director at NICE said: « The independent Appraisal Committee could not assess whether bortezomib in combination with dexamethasone is a cost-effective treatment option because it did not have sufficient information to do so. The next step in the NICE process is for the manufacturer to consider the Committee’s comments and respond to its request for further evidence. »
Consultees, including the manufacturer, healthcare professionals and members of the public are now able to comment on the preliminary recommendations which are available for public consultation. Comments received during this consultation will be fully considered by the Committee and following this meeting the next draft guidance will be issued.
Until final guidance is issued, NHS bodies should make decisions locally on the funding of specific treatments. Once NICE issues its final guidance on a technology, it replaces local recommendations across the country.
1. The draft guidance will be available from 12 November 2013. Embargoed copies of the draft guidance are available from the NICE press office on request.
2. The cost of bortezomib is £762.38 per 3.5 mg vial. The average cost of a course of treatment with bortezomib given with dexamethasone is estimated to be £12,260.91 and the average cost of a course of treatment with bortezomib given with dexamethasone and thalidomide is estimated to be £24,840.10.
3. The Committee agreed that treatment with bortezomib and dexamethasone was associated with statistically significant improvements in post-induction overall response rates compared with vincristine, adriamycin and dexamethasone, whereas induction treatment with bortezomib, thalidomide and dexamethasone resulted in statistically significant improvements in overall response rates (post-induction and post-stem cell transplantation) and progression-free survival compared with thalidomide and dexamethasone. However, it concluded that no direct evidence was available to compare the efficacy of bortezomib, thalidomide and dexamethasone or bortezomib and dexamethasone with cyclophosphamide, thalidomide and dexamethasone, the comparator regimen considered to be current standard of care in the UK.
4. The most plausible cost per quality-adjusted life year (QALY) for bortezomib, thalidomide and dexamethasone compared with cyclophosphamide, thalidomide and dexamethasone was likely to be substantially higher than the £39,000 per QALY compared with thalidomide and dexamethasone.
5. NICE already recommends bortezomib as an option for the treatment of progressive multiple myeloma in people who are at first relapse having received one prior therapy and who have undergone, or are unsuitable for, bone marrow transplantation. NICE Technology Appraisal 129
6. Thalidomide in combination with an alkylating agent and a corticosteroid is recommended as an option for the first-line treatment of multiple myeloma in people for whom high-dose chemotherapy with stem cell transplantation is considered inappropriate. Bortezomib (Velcade, Janssen) is also recommended under these circumstances, if the person is unable to tolerate or has contraindications to thalidomide. NICE Technology Appraisal 228
7. Lenalidomide in combination with dexamethasone is recommended as a treatment option for people with multiple myeloma who have received two or more prior therapies.
About NICE
The National Institute for Health and Care Excellence (NICE) is the independent body responsible for driving improvement and excellence in the health and social care system. We develop guidance, standards and information on high-quality health and social care. We also advise on ways to promote healthy living and prevent ill health.
Formerly the National Institute for Health and Clinical Excellence, our name changed on 1 April 2013 to reflect our new and additional responsibility to develop guidance and set quality standards for social care, as outlined in the Health and Social Care Act (2012).
Our aim is to help practitioners deliver the best possible care and give people the most effective treatments, which are based on the most up-to-date evidence and provide value for money, in order to reduce inequalities and variation.
Our products and resources are produced for the NHS, local authorities, care providers, charities, and anyone who has a responsibility for commissioning or providing healthcare, public health or social care services.
To find out more about what we do, visit our website: and follow us on Twitter: @NICEComms.


FDA approves Roche’s Gazyva (obinutuzumab) for people with previously untreated chronic lymphocytic leukemia (CLL)

Gazyva demonstrated an 84 percent reduction in the risk of disease worsening or death when combined with chemotherapy compared to chemotherapy alone
Gazyva is the first medicine approved with the FDA’s Breakthrough Therapy Designation
Roche (SIX: RO, ROG; OTCQX: RHHBY) today announced that the U.S. Food and Drug Administration (FDA) approved Gazyva (obinutuzumab), also known as GA101, in combination with chlorambucil chemotherapy for the treatment of people with previously untreated chronic lymphocytic leukemia (CLL). Gazyva is the first medicine approved with the FDA’s Breakthrough Therapy Designation and the fifth cancer medicine from Roche approved by the FDA in the past three years.
“Gazyva is an important new medicine for people with newly diagnosed chronic lymphocytic leukemia as based on clinical data, it more than doubled the time people lived without their disease worsening compared to chlorambucil alone,” said Hal Barron, M.D., chief medical officer and head of Global Product Development. “We have spent 20 years researching blood cancer medicines, and we will continue to study Gazyva to assess its efficacy in other types of blood cancers.”
The FDA granted Gazyva Breakthrough Therapy Designation due to the significance of the positive progression-free survival (PFS) results from the Phase III CLL11 trial and the serious and life-threatening nature of CLL.
Today’s FDA approval is based on the outcomes of the CLL11 trial. The trial showed that people who received Gazyva in combination with chlorambucil chemotherapy had significantly reduced risk of disease progression or death (HR=0.16; p<0.0001) and lived significantly longer without their disease getting worse compared to those who received chlorambucil alone (median PFS 23.0 months vs. 11.1 months). The most common Grade 3/4 adverse events for those who received Gazyva in combination with chlorambucil compared to chlorambucil alone were infusion-related reactions during the first infusion (21 percent vs. 0 percent [chlorambucil is an oral medicine]), low platelet count (thrombocytopenia, 11 percent vs. 3 percent) and low count of certain types of white blood cells (neutropenia, 34 percent vs. 16 percent), though this did not result in an increased rate of infections in the Gazyva arm.
Final data from the CLL11 trial investigating the direct comparison between Gazyva in combination with chlorambucil and MabThera/Rituxan (rituximab) in combination with chlorambucil (Stage 2), will be presented at the American Society of Hematology’s (ASH) 55th Annual Meeting in December 2013
Marketing applications have also been submitted to other regulatory authorities, including the European Medicines Agency (EMA).

About Chronic Lymphocytic Leukemia (CLL)
CLL is one of the most common forms of blood cancer and in 2013, it is expected that there will be nearly 5,000 deaths from CLL in the United States. Most cases of CLL (95 percent) start in white blood cells called B-cells that have a protein called CD20 on their surface.

About Gazyva
Gazyva is a new monoclonal antibody designed to attach to CD20, a protein found only on B-cells. It attacks targeted cells both directly and together with the body’s immune system.
Gazyva was discovered by Roche Glycart AG, a wholly owned, independent research unit of Roche. In the United States, Gazyva is part of a collaboration between Genentech and Biogen Idec.

Gazyva is now approved in combination with chlorambucil for people with previously untreated chronic lymphocytic leukemia (CLL) and is additionally being investigated in a large clinical programme, including multiple head-to-head Phase III studies compared to MabThera/Rituxan in indolent non-Hodgkin lymphoma (NHL) and diffuse large B-cell lymphoma (DLBCL).

Gazyva Efficacy in CLL
The pivotal Phase III CLL11 trial, conducted in cooperation with the German CLL Study Group (GCLLSG), is a multicentre, open-label, randomised three-arm study investigating the efficacy and safety profile of either Gazyva plus chlorambucil or MabThera/Rituxan plus chlorambucil compared to chlorambucil alone in 781 previously untreated people with CLL and co-existing medical conditions.
The study showed that Gazyva demonstrated a statistically significant 84 percent reduction in the risk of disease worsening or death (PFS; HR=0.16, 95 percent CI 0.11-0.24, p<0.0001) when combined with chlorambucil compared to chlorambucil alone in people with previously untreated CLL and co-existing medical conditions. In the CLL11 study, no new safety signals were detected for Gazyva.
Gazyva in combination with chlorambucil more than doubled the time people with newly diagnosed CLL lived without their disease getting worse (median PFS: 23.0 vs. 11.1 months).
75.9 percent of people responded to Gazyva in combination with chlorambucil (overall response rate, or ORR) compared to 32.1 percent with chlorambucil alone.
More than a quarter of the people who received Gazyva in combination with chlorambucil achieved a complete response (CR: 27.8 percent vs. 0.9 percent).

About Roche in hematology

For more than 20 years, Roche has been developing medicines that redefine treatment in hematology. Today, we’re investing more than ever in our effort to bring innovative treatment options to people with cancers of the blood.
In addition to Gazyva, Roche’s pipeline of potential hematology medicines includes two antibody-drug conjugates (anti-CD79b [RG7596] and anti-CD22 [RG7593]), a small molecule antagonist of MDM2 (RG7112) and in collaboration with AbbVie, a small molecule BCL-2 inhibitor (RG7601/GDC-0199/ABT-199).

Source: Roche

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