MSD Anti-PD1 Drug Announcement

Encouraging press release and information on MSD's new Anti-PD-1 Immunotherapy for advanced melanoma.

Additional Interim Data for MSD’s Investigational Anti-PD-1 Immunotherapy,
MK-3475, Shows Estimated Overall Survival Rate of 81 per cent at One Year in Patients with Advanced Melanoma


Hoddesdon,18^th November 2013 – Merck (NYSE: MRK), known as MSD outside the United States and Canada, has announced additional data for MK-3475, an investigational anti-PD-1 immunotherapy, in patients with advanced melanoma that showed an estimated overall survival rate of 81 per cent at one year across all MK-3475 monotherapy doses evaluated. This is the first time overall survival data have been presented from the cohort of 135 patients with advanced melanoma enrolled in MSD’s ongoing Phase IB clinical trial (PN 001) for MK-3475. Researchers presented the findings in an oral plenary session at the 10th International Congress of the Society for Melanoma Research in Philadelphia.
“New agents are needed for patients with advanced melanoma,” said Dr. Caroline Robert, head of Dermatology at Gustave Roussy, Cancer Campus, Grand Paris. “I am excited by the results seen for MK-3475 to date as a single agent and believe these findings support further study both as a monotherapy and in combination in various solid tumours.”
The objective response rate (patients who had either a complete or partial response) across all doses improved with longer duration of follow-up; at the time of this analysis, the objective response rate was 41 per cent (9 per cent complete response rate), as evaluated by a blinded central review committee using RECIST 1.1 (Response Evaluation Criteria in Solid Tumours). While the majority of responses to MK-3475 treatment occurred early (within the first 12 weeks), responses and changes from partial to complete response continued to occur after six months of treatment. Partial and complete responses occurred as late as 48 and 70 weeks. Median duration of response and median overall survival have yet to be reached for any dose evaluated.
Dr. James Larkin, Consultant Medical Oncologist, The Royal Marsden, “I am extremely encouraged by the results observed to date, including the rate and duration of responses, in patients with advanced melanoma on this trial.  The prospect and outcome for people with this type of advanced melanoma cancer looks very promising using immunotherapy.”
“These results provide further insight into the therapeutic properties of MK-3475 in patients with advanced melanoma,” said Dr. Roger M. Perlmutter, president, MSD Research Laboratories. “Simply put, our data make us hopeful that this novel investigational therapy could potentially provide meaningful benefits to patients suffering from this malignant disease.”

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Note to Editors

For more information, please contact: 
Suzie Collett, Merck Sharp & Dohme Limited at susan.collett@merck.com T: + 44 (0)1992 455471
OR Louise Collins, Reynolds MacKenzie, T: +44 (0)207 861 2813 M: +44 (0)7584 560 584 louise.c@reynoldsmackenzie.com

Phase 1B Trial (PN 001) Trial Design
The Phase IB trial (PN 001) is an ongoing multi-centre, single-arm, open-label study evaluating MK-3475 monotherapy in more than 1,000 patients with diverse late-stage cancers (metastatic carcinoma)—predominantly lung and melanoma. Three dosing regimens of MK-3475 were evaluated, including 10mg/kg every two weeks, 10mg/kg every three weeks or 2mg/kg every three weeks. The primary endpoint of the study is overall response rate and the secondary endpoints are progression-free survival and overall survival as measured by immune-related response criteria and centrally evaluated RECIST criteria.

Additional Results for MK-3475 in Advanced Melanoma
This additional analysis provides approximately five months of follow-up for objective response rate beyond the interim results for MK-3475 from the 135 patients in the advanced melanoma cohort presented at the 2013 American Society of Clinical Oncology (ASCO) Annual meeting and published in the New England Journal of Medicine. In addition, this is the first time overall survival and progression-free survival have been presented from this study.
The previously reported objective response rate across all doses was 38 per cent (CI 95%: 25 to 44 per cent) (per RECIST criteria). In the analysis presented today, the overall response rate was 41 per cent (CI 95%: 32 to 51 per cent), reflecting additional responses to MK-3475. In addition, 88 per cent (43/49) of patients with a partial or complete response showed no evidence of disease progression. Similar response rates were observed between ipilimumab-pre-treated and ipilimumab-naïve patients.
At this analysis, the maximum ongoing duration of response recorded was 65 weeks (range 8+ to 65+). The disease control rate across doses for patients in the melanoma cohort was 61 per cent (CI 95%: 52 to 70 per cent), and median progression-free survival at time of analysis was 36 weeks. The rates of treatment-related adverse events were consistent with those previously observed and included: fatigue (37%), pruritus (26%), rash (22%), diarrhoea (21%), arthralgia (17%), vitiligo (14%), headache (13%), nausea (12%), asthenia (11%), myalgia (11%) and AST increase (10%). Grade 3–4 treatment-related adverse events that occurred in more than one patient were AST increase, fatigue, rash and renal failure (n=2 each).

Clinical Development of MK-3475 in Advanced Melanoma
MSD has completed enrolment in a Phase II registration trial (PN 002) comparing two doses of MK-3475 versus chemotherapy in patients with advanced melanoma who have progressed after prior therapy (see clinicaltrials.gov). A Phase III registration trial of MK-3475 versus ipilimumab in ipilimumab-naïve patients with advanced melanoma is ongoing (see clinicaltrials.gov). The company plans to initiate combination trials this year and in early 2014 in melanoma and other cancers.

About MK-3475
Many tumours are able to evade the immune system through a mechanism that exploits the PD-1 inhibitory checkpoint protein. MK-3475 is an investigational, highly selective anti-PD-1 immunotherapy designed to restore the natural ability of the immune system to recognise and target cancer cells by selectively achieving dual ligand blockade (PD-L1 and PD-L2) of the PD-1 protein. By blocking PD-1, MK-3475 enables activation of the immune system’s T-cells that target cancer by essentially releasing a brake on the immune system.
MK-3475 is currently being studied in eight clinical trials estimated to enrol over 3,000 patients across a broad range of cancer types, including: bladder, colorectal, gastric, head and neck, melanoma, non-small cell lung, triple negative breast and haematological malignancies. Additional trials, both as monotherapy and in combination with other cancer therapies, are planned. The expansion of the MK-3475 clinical development program is based on preliminary clinical evidence from MSD’s large foundational Phase IB trial (PN 001) evaluating MK-3475 monotherapy in more than 1,000 patients with diverse late-stage cancers (metastatic carcinoma).

About Breakthrough Therapy Designation
In April 2013, MSD announced that MK-3475 received a Breakthrough Therapy Designation for advanced melanoma from the U.S. Food and Drug Administration (FDA). This designation for an investigational drug is intended to expedite the development and review of a candidate that is planned for use, alone or in combination, to treat a serious or life-threatening disease or condition when preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over existing therapies on one or more clinically significant endpoints. The U.S. FDA Safety and Innovation Act include a provision that allows sponsors to request that an investigational drug be designated as a Breakthrough Therapy.

Advanced Melanoma
There are two types of skin cancer: malignant melanoma which is less common but more serious; and non-melanoma skin cancer, which is more common but not as serious. Around 12,800 cases of malignant melanoma were diagnosed in 2010 in the UK, that’s around 35 people every day. Malignant melanoma incidence rates in the UK have more than quadrupled over the last thirty years. Like most cancers, skin cancer is more common with increasing age, but malignant melanoma is disproportionately high in younger people. More than one third of all cases of malignant melanoma occur in people under 55. Advanced melanoma means the cancer has spread from where it started to another part of the body. Advanced melanoma includes unresectable stage III or metastatic melanoma (stage IV)

Please refer to link below (Cancer Research UK) for more information about advanced melanoma cancer, and the incidence in the UK.

http://www.cancerresearchuk.org/cancer-help/type/melanoma/
http://publications.cancerresearchuk.org/downloads/Product/CS_KF_SKIN.pdf

About MSD
We believe the most important thing we make is a difference. We operate in more than 140 countries and through our prescription medicines, vaccines, biologic therapies, and consumer care and animal health products we work with customers to bring innovative healthcare solutions to those who need them the most. We also demonstrate our commitment to increasing access to healthcare through far-reaching policies, programmes and partnerships. For more information visit www.msd-uk.com.  MSD is a trade name of Merck & Co., Inc., with headquarters in Whitehouse Station, N.J., U.S.A.

MSD Forward-Looking Statement
This news release includes “forward-looking statements” within the meaning of the safe harbour provisions of the United States Private Securities Litigation Reform Act of 1995. These statements are based upon the current beliefs and expectations of MSD’s management and are subject to significant risks and uncertainties. There can be no guarantees with respect to pipeline products that the products will receive the necessary regulatory approvals or that they will prove to be commercially successful. If underlying assumptions prove inaccurate or risks or uncertainties materialize, actual results may differ materially from those set forth in the forward-looking statements.
Risks and uncertainties include, but are not limited to, general industry conditions and competition; general economic factors, including interest rate and currency exchange rate fluctuations; the impact of pharmaceutical industry regulation and healthcare legislation in the United States and internationally; global trends toward healthcare cost containment; technological advances, new products and patents attained by competitors; challenges inherent in new product development, including obtaining regulatory approval; MSD’s ability to accurately predict future market conditions; manufacturing difficulties or delays; financial instability of international economies and sovereign risk; dependence on the effectiveness of MSD’s patents and other protections for innovative products; and the exposure to litigation, including patent litigation, and/or regulatory actions.
MSD undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise. Additional factors that could cause results to differ materially from those described in the forward-looking statements can be found in MSD’s 2012 Annual Report on Form 10-K and the company’s other filings with the Securities and Exchange Commission (SEC) available at the SEC’s Internet site (www.sec.gov).

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