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

Roche Cancer Vaccine Pact Could Net Immatics $1B

Roche will oversee clinical development and commercialization of all immunotherapies generated by immatics biotechnologies under a cancer vaccine and immunotherapy collaboration that could net the German clinical-stage biopharma more than $1 billion.

Roche agreed to pay immatics $17 million up-front and additional unspecified committed research funding, plus more than $1 billion in milestone payments and royalties across three cancer indications, to be based on sales of the cancer vaccines and immunotherapies resulting from the companies’ collaboration.

The collaboration will focus on research, clinical development, and commercialization of a number of new tumor-associated peptide (TUMAP)-based cancer vaccine candidates and other immunotherapies in oncology, targeting primarily gastric, prostate, and non-small cell lung cancer. Furthest along in development among the candidates is IMA942, for gastric cancer, which according to the companies is ready for Phase I trials.

Also as part of the collaboration, immatics will use its XPRESIDENT® technology platform to identify TUMAP candidates for development of cancer vaccines and other compounds targeting cancer peptide antigens, primarily in gastric, prostate, and non-small cell lung cancer. According to the companies, XPRESIDENT is the only known high-throughput research technology capable of directly identifying, quantifying, and prioritizing cancer antigens recognized by T lymphocytes based on the ability of the immune system to detect them.

“The wealth of relevant cancer-specific antigens that we expect to emerge from this research collaboration will provide an extraordinary opportunity to elicit broad tumor-specific immune responses upon vaccination, especially when combined with other immunomodulatory molecules in our pipeline,” Hy Levitsky, Roche’s head of cancer immunology experimental medicine, said in a statement. “Discovery of novel antigens also will provide unique targets for other protein-based anti-cancer agents currently under development.”

immatics’ collaboration with Roche comes about a month after the company won €34 million ($46 million) in Series D financing—of which €12 million ($16 million) will be received immediately—to conclude development of its lead vaccine IMA901, now in a Phase III trial, including completing all activities needed to prepare for regulatory filings in the United States and Europe.

IMA901 is a cancer vaccine consisting of 10 TUMAPs found to be highly overexpressed in the majority of patients suffering from renal cell carcinoma (RCC). The vaccine has U.S. and European orphan drug designations for treating RCC in HLA-A*02 positive patients. The Phase III trial is designed to evaluate overall survival with IMA901 in combination with Pfizer ‘s Sutent® (sunitinib), the current standard first-line therapy, compared with sunitinib alone in patients with metastatic and/or locally advanced RCC. A total of 339 patients are enrolled in the trial, which is expected to generate interim overall survival results in 2014, with final data in 2015.

Source : genengnews

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

FDA approves Roche’s Kadcyla (trastuzumab emtansine), the first antibody-drug conjugate for treating HER2-positive metastatic breast cancer

New personalised medicine helped people in Phase III study live longer, compared to standard treatment

Roche  announced that the U.S. Food and Drug Administration (FDA) has approved Kadcyla (trastuzumab emtansine or T-DM1) for the treatment of people with HER2-positive metastatic breast cancer (mBC) who have received prior treatment with Herceptin (trastuzumab) and a taxane chemotherapy. Kadcyla is the fourth medicine from Roche to receive FDA approval for people with advanced cancers within the past two years.

An antibody-drug conjugate (ADC) is a new kind of targeted cancer medicine that can attach to certain types of cancer cells and deliver chemotherapy directly to them. Kadcyla is the first FDA-approved ADC for treating HER2-positive mBC, an aggressive form of the disease.

“Kadcyla is an antibody-drug conjugate representing a completely new way to treat HER2-positive metastatic breast cancer, and it helped people in the EMILIA study live nearly six months longer,” said Hal Barron, M.D., Roche’s Chief Medical Officer and Head, Global Product Development. “We currently have more than 25 antibody-drug conjugates in our pipeline and hope this promising approach will help us deliver more medicines to fight other cancers in the future.”

Kadcyla is made up of the antibody, trastuzumab, and the chemotherapy, DM1, joined together using a stable linker. Kadcyla combines the mechanisms of action of both trastuzumab and DM1, and it is the first Roche ADC approved by the FDA. Roche has studied ADC science for more than a decade and has eight ADCs in Phase I or Phase II studies for different types of cancer.

Roche has also submitted a Marketing Authorisation Application to other Regulatory Authorities around the world, including the European Medicines Agency (EMA), for Kadcyla for the treatment of people with HER2-positive mBC. This application is currently under review by the EMA.

Kadcyla efficacy in HER2-positive mBC

The FDA approval of Kadcyla is based on results from EMILIA (TDM4370g/BO21977), an international, Phase III, randomised, open-label study comparing Kadcyla alone to lapatinib in combination with Xeloda (capecitabine) in 991 people with HER2-positive locally advanced breast cancer or mBC who had previously been treated with Herceptin and a taxane chemotherapy. Results include:1

  • The study met both co-primary efficacy endpoints of overall survival and progression-free survival (PFS; as assessed by an independent review committee).
  • People who received Kadcyla lived a median of 5.8 months longer (overall survival) than those who received the combination of lapatinib and Xeloda, the standard of care in this setting (median overall survival: 30.9 months vs. 25.1 months).
  • People receiving Kadcyla experienced a 32 percent reduction in the risk of dying compared to people who received lapatinib and Xeloda (HR=0.68; p=0.0006).
  • People who received Kadcyla lived significantly longer without their disease getting worse (PFS) compared to those who received lapatinib plus Xeloda (HR=0.65, 35 percent reduction in the risk of disease worsening or death, p<0.0001; median PFS 9.6 months vs. 6.4 months).
  • No new safety signals were observed and adverse events (AEs) were consistent with those seen in previous studies, with fewer people who received Kadcyla experiencing Grade 3 or higher (severe) AEs than those who received lapatinib plus Xeloda (43.1 percent vs. 59.2 percent).
  • For people receiving Kadcyla, the most common (occurring in more than 2 percent of participants) Grade 3 or higher AEs were low platelet count (14.5 percent), increased levels of enzymes released by the liver and other organs (8.0 percent), low red blood cell count (4.1 percent), low levels of potassium in the blood (2.7percent), nerve problems (2.2percent) and tiredness (2.5percent).

 

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

FDA approves Erivedge (vismodegib) capsule, the first medicine for adults with advanced basal cell carcinoma

Erivedge is a first-in-class Hedgehog Pathway Inhibitor that helps shrink disfiguring or potentially life-threatening lesions in advanced skin cancer

Roche (SIX: RO, ROG; OTCQX: RHHBY) today announced that Erivedge (vismodegib) capsule was approved by the U.S. Food and Drug Administration (FDA) for adults with a type of skin cancer, called basal cell carcinoma (BCC), that has spread to other parts of the body or that has come back after surgery or that their healthcare provider decides cannot be treated with surgery or radiation. Erivedge is the first FDA-approved medicine for people with advanced forms of the most common skin cancer. It is a capsule that is taken orally once-a-day.

Basal cell carcinoma is generally considered curable if the cancer is restricted to a small area of the skin. However, in rare cases, lesions can become disfiguring and invade surrounding tissue (locally advanced) or spread to other parts of the body (metastasize). In these cases of advanced BCC, the disease cannot be effectively treated with surgery or radiation. Advanced BCC often results in severe deformity or loss of function of affected organs.

“Today’s approval provides a new treatment for people with advanced basal cell carcinoma who, until now, had no approved medicines to help shrink disfiguring or potentially life-threatening lesions,” said Hal Barron, M.D., Chief Medical Officer and Head, Global Product Development. “We are pleased that in the last six months we have been able to provide two new medicines for different types of advanced skin cancer to people who previously had few or no treatment options.”

 

Source: Roche

CHMP recommends EU approval of Roche’s Subcutaneous Herceptin for HER2 positive breast cancer

  • New injectable administration takes two to five minutes, rather than 30 to 90 minutes with the current intravenous form, potentially saving both healthcare resources and patients’ time
  • Herceptin® is a personalised medicine used to treat more than 80,000 HER2-positive breast cancer patients in Europe each year

Roche (SIX: RO, ROG; OTCQX: RHHBY) is pleased to announce that the European Union’s Committee for Medicinal Products for Human Use (CHMP) has today recommended EU approval of a subcutaneous formulation of Herceptin® (trastuzumab) for the treatment of patients with HER2-positive breast cancer. Since Herceptin’s first approval in 1998 this targeted medicine has been used to treat more than 1.3 million patients worldwide.

At present, Herceptin is given to patients intravenously, which takes 30 to 90 minutes per dose. By contrast, the new subcutaneous formulation of Herceptin can be administered in two to five minutes by a simple injection under the skin.1

« Over the last 14 years, Herceptin has revolutionised the treatment of HER2-positive breast cancer. Today, more than 80,000 patients in Europe receive Herceptin each year,” said Hal Barron, MD, Roche’s Chief Medical Officer and Head of Global Product Development. “EU approval of this subcutaneous form of Herceptin would provide a more convenient option for patients that potentially saves time and healthcare resources. »

The CHMP’s positive opinion was based on data from the pivotal phase III HannaH study which showed the efficacy and safety of the subcutaneous formulation of Herceptin were comparable to treatment with Herceptin administered intravenously.1

The subcutaneous formulation of Herceptin uses technology developed by Halozyme Therapeutics, Inc. that reversibly breaks down hyaluronan, a gel-like substance that forms a barrier between cells under the skin. This enables the relatively large volume of the subcutaneous formulation of Herceptin to be rapidly dispersed over a greater area.

Roche is working with regulatory authorities around the world to ensure patients who are eligible for treatment with Herceptin have the option of choosing this more convenient therapy.

 

Source: Roche