Research and Development Monitor Melanoma - Drug resistance provides an opportunity for drug developers

• Publication date: May 2012
• Report size: 40 pages

The melanoma industry has seen a large increase in developer attention following breakthroughs in treatment over the past year. Datamonitor has identified 108 drugs in the melanoma pipeline, with 7% in Phase III and 49% in Phase II trials. Early-stage developers are focusing on new targets in the MAPK pathway and immunomodulator targets such as PD-1 in an attempt to limit take over d resistance....

The melanoma industry has seen a large increase in developer attention following breakthroughs in treatment over the past year. Datamonitor has identified 108 drugs in the melanoma pipeline, with 7% in Phase III and 49% in Phase II trials. Early-stage developers are focusing on new targets in the MAPK pathway and immunomodulator targets such as PD-1 in an attempt to limit take over d resistance.In-depth analysis of melanoma pipeline – development stage, therapeutic class, molecular targets, and changes in pipeline since 2010In-depth analysis of current comparator therapy – target product profile, unmet needs, and innovative early-stage approachesIn-depth analysis of clinical trial design – patient selection, duration, clinical endpoints, and future developments in trial designThe future of melanoma treatment – combination therapies, increasing use of biomarkers, and novel targeted therapiesThe Phase III pipeline currently contains four immunotherapies, three targeted therapies, and one cytotoxic. Development of two new targeted therapies in metastatic patients with the BRAF V600E mutation will position them in direct competition with Roche/Daiichi Sankyo’s drug Zelboraf (vemurafenib).Clinical trial design must evolve to keep up with the shift in the melanoma industry toward targeted therapies and immunotherapies. Correct patient selection for clinical trials is even more important now that patients are being sector ed by BRAF mutation. Trial endpoints will also be more important as treatment efficacy continues to improve.Future melanoma treatment will rely on new combination therapies to prevent development of drug resistance. Ongoing trials evaluating combination therapies such as Yervoy and Zelboraf or BRAF and MEK inhibitors could help to bridge the gaps in current therapy approaches.Identify major trends and drivers in the melanoma pipeline, including development stage, molecular targets, and therapeutic classIdentify the target product profile for new melanoma therapies and innovative early-stage drug targetsAssess key decisions in melanoma clinical trial design regarding patient selection, trial duration, endpoints, and predictive biomarkers

Drug Discovery And Development Industry

OVERVIEW•Catalyst
•Summary

EXECUTIVE SUMMARY•Strategic scoping and focus
•Datamonitor key findings
•Related reports

CLINICAL PIPELINE OVERVIEW•Overview of the melanoma pipeline - Datamonitor has identified 108 drugs in development for melanoma

•Late-stage development compounds recently discontinued - Genasense (oblimersen; Genta)
- Tasisulam (LY573636; Eli Lilly)

TARGET PRODUCT PROFILE•Yervoy (ipilimumab; Bristol-Myers Squibb)
•Zelboraf (vemurafenib; Roche/Daiichi Sankyo)
•Target product profile versus current level of attainment - Unmet needs in melanoma
- The ability of Yervoy and Zelboraf to meet unmet needs in first-line metastatic melanoma

CLINICAL TRIAL DESIGN IN MELANOMA•Clinical trials - Clinical trial design
- Patient selection
- Clinical trial duration
- Clinical trial endpoints in cancer

•Future developments in clinical trial design - The diversity of targeted therapies will require an evolution in clinical trial design

INNOVATIVE EARLY-STAGE APPROACHES•Early-stage pipeline - MAPK pathway
- PD-1 and PD-L1

THE FUTURE OF TREATMENT IN MELANOMA•Combination therapies - Newly approved therapies have limitations despite improving overall survival

•Increasing use of biomarkers - Biomarkers will play an important role in patient selection

BIBLIOGRAPHY•Journal papers
•Websites
•Datamonitor reports
•Other

APPENDIX•Contributing experts
•Report methodology

TABLES•Table: Phase III pipeline products in development for melanoma, 2012
•Table: Recently discontinued drugs in melanoma, 2012
•Table: Yervoy (ipilimumab; Bristol-Myers Squibb) – drug presentation, 2012
•Table: Zelboraf (vemurafenib) – drug presentation, 2012
•Table: Ability of Yervoy to meet unmet needs in first-line metastatic melanoma
•Table: Ability of Zelboraf to meet unmet needs in first-line BRAF V600E -positive metastatic melanoma
•Table: Phase III trial design for Zelboraf, 2011
•Table: Advantages and limitations of melanoma trial endpoints
•Table: Top five early-stage melanoma drug targets, 2012
•Table: MEK inhibitors currently in Phase I and II trials for melanoma, 2012
•Table: PD-1 and PD-L1 inhibitors in Phase I and II trials for melanoma, 2012

FIGURES•Figure: Melanoma clinical pipeline, by development stage, 2012
•Figure: Pipeline melanoma therapies, by therapeutic class and phase, 2012
•Figure: Melanoma clinical pipeline, by development stage, 2010–12
•Figure: Change in melanoma pipeline, by therapeutic class, 2010–12
•Figure: Drug and companion diagnostic co-development process key steps
•Figure: Early-stage melanoma pipeline, by drug class, 2012
•Figure: An illustrative comparison of patient survival when treated with an immunomodulator or BRAF inhibitor

Companies mentioned

Delta Air Lines, Inc., Devoteam SA, GlaxoSmithKline Plc, Hutchison 3G UK Limited, Kewill plc, SCC