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

Oncology Market Forecast, what are the key challenges ?

Oncology will remain by far the largest segment until 2018, with strong growth from both inline products and new products, off-setting a number of major patent expiries over the period. 

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The great commercial success experienced by cancer therapies leaders(Roche, Sanofi, Novartis, AstraZeneca, and Eli Lilly) makes the market extremely attractive for the drug developers. The treatment of cancer has shifted away from mass market blockbuster drugs toward a more focused attack on the disease with targeted therapies. However, the crisis, and the austerity packages imposed by healthcare authorities could see slower commercial growth and larger generic erosion of key brands princeps.

The Hoffmann – Kruger analysis is shows that Roche is by far the dominant player in the world wide oncology market, 2012 with 35% market share in 2012. Roche is expected to remain the oncology leader until 2018. Although the low growth rate of Roche portfolio is due to the potential entry of biosimilar Herceptin and Rituxan between 2012 and 2018.

Roche has consolidated its position as the global leader in this sector via acquisitions (e.g. Genentech) or licensing agreements. Roche’s R&D strategy rests on developing well-differentiated personalized medicines built on an understanding of disease biology. Novartis’ oncology strategy is moving away from a blockbuster-driven structure and has diversified its portfolio to include novel targeted agents that address numerous pathways and cancer types, as well to a lesser degree as the older hormonal and supportive care agents. Amgen is looking to strengthen its presence in oncology. Recent acquisitions have been geared toward this goal and added a diverse array of technologies. The BioVex deal added the cytolytic, live-virus vaccine T-VEC (OncoVex) which is in Phase III for melanoma, while the Abgenix acquisition added earlier-stage small molecules and MAb. Sanofi has actively sought oncology-focused late-stage licensing deals, but many of these programs have ended quickly. Small acquisitions, such as BiPar and TargeGen, have also been used to supplement the portfolio, while the acquisition of Genzyme provided a presence both in hematological malignancies.

AstraZeneca had shunned biologics, as well as in-licensing, preferring to concentrate on internal/acquired R&D of small molecules. The 2003 research alliance with Abgenix (now part of Amgen) to develop human oncology monoclonal antibodies against oncology indications was the company’s first foray into biologics. The subsequent acquisitions of KuDos (2005), CAT (2006) and MedImmune (2007) have strengthened the oncology biologics pipeline To improve its future in oncology, J&J established Ortho Biotech Oncology Research & Development to unite the efforts of several J&J companies in the development of oncology and hematology small molecules and biologics. The company aims to bolster its hematological malignancy pipeline and in December 2011, in-licensed worldwide rights to Pharmacyclics novel BTK-inhibitor, PCI-32765. This candidate is in development for B-cell malignancies including chronic lymphocytic leukemia, mantle cell lymphoma and diffuse B-cell lymphoma.

In September 2009, Eli Lilly established two therapeutic business units, one of which focuses on Oncology, demonstrating the high strategic importance of this field. The acquisition of ImClone for $6.5b in November 2008, was driven by the company’s ambitions to expand in oncology. This brought royalties and milestone payments from BMS and Merck KGaA for Erbitux, and rights to its late-stage pipeline, including ramucirumab. In December 2011, Lilly signed an antibody drug conjugate deal with Immunogen to use their maytasanoid Targeted Antibody Payload (TAP) technology with existing Lilly monoclonal antibodies, to develop novel antibody-drug conjugate cancer treatments.

Pfizer has built an oncology portfolio via acquisitions (e.g. Pharmacia and Wyeth, and smaller transactions such as Serenex, CovX and Coley). It established an oncology business unit in 2008; its R&D is focused on Biologics & Targeted Agents and its diverse pipeline addresses numerous targets but so far has failed to progress any biologics to market after a number of high-profile, late-stage failures (e.g. figitumumab, remelimumab and ProMune). The development of Xalkori established Pfizer as one of the forerunners in personalized medicine for lung cancer; it is advancing molecular testing in the disease and is exploring further opportunities in both lung cancer and into oncology genomics more generally. BMS has actively sought to develop a strong and broad oncology franchise, establishing a powerful network of contacts within the oncology community from early-stage research with universities and research institutes, through to commercialization and marketing. The company is focused on immuno-oncology; it launched Yervoy in 2011 and has several candidates in clinical trials with potential utility across a range of tumor types.

 

Regarding this element, the statistical analysis, and the KOL interviews we can be sure about the market results,  but as Winston Churchill said: 

« The most essential qualification for a politician is the ability to foretell what
will happen tomorrow, next month, and next year, and to explain afterwards
why it did not happen« 

 

Elena Kienesberger
elena.k@hoffmann-krueger.com 

Oncology-analysis