MERCK KGAA:STUDY SHOWS CILENGITIDE INCREASED OVERALL SURVIVAL

(BW)(FL-MERCK)

Merck KGaA: Study Shows Cilengitide Increased Overall
Survival in Patients With Glioblastoma

Data presented at ASCO support investigation of cilengitide
in Phase III study, CENTRIC, for patients with newly diagnosed
glioblastoma multiforme

Health/Medical Writers

ORLANDO, Fla. & DARMSTADT, Germany--(BUSINESS WIRE) - May.
31, 2009-- Results from an independent Phase II study of
patients with newly diagnosed glioblastoma multiforme (GBM)
show that cilengitide given in combination with
chemoradiotherapy (concomitant and adjuvant temozolomide with
radiotherapy) may extend survival.1 These findings were
presented at the annual meeting of the American Society of
Clinical Oncology (ASCO) in Orlando.

Demonstrating the commitment of Merck KGaA, Darmstadt,
Germany, to personalizing cancer care with innovative, targeted
therapies, cilengitide is the first in a new class of
investigational anti-cancer therapies called integrin
inhibitors having reached Phase III development. These are
thought to work by targeting tumor cells and the vascular
network required to nourish the tumor and promote cancer cell
growth.

The NABTT-0306 study, sponsored by the National Cancer
Institute and run by the New Approaches to Brain Tumor Therapy
(NABTT) Adult Brain Tumor Consortium, randomized 94 patients
with newly diagnosed GBM to two different doses of cilengitide
(500 or 2,000 mg) in combination with chemoradiotherapy to
estimate overall survival as the primary endpoint.

Secondary endpoints included progression-free survival and a
safety assessment of this regimen. Prior to the randomized part
of the study, a safety run-in phase involving 18 patients was
completed as planned at 500, 1,000, and 2,000 mg dose levels.

The primary endpoint results demonstrated a trend towards
increased overall survival in the 2,000 mg dose study arm
compared to the 500 mg dose cilengitide study arm. Pooling
together the results from both treatment arms, patients in this
randomized study experienced a median survival time of 18.9
months (95% CI 16.6?21.9), with an overall survival rate at
12-month follow-up of 79.5% (95% CI 71?87).1 In historical
controls in this setting, median survival time and 12-month
survival rate with chemoradiotherapy alone have been reported
as 14.6 months and 61.1% (95% CI 55 67), respectively.2 "We are
encouraged by these results. Glioblastoma is a highly
aggressive and challenging cancer type with very poor prognosis
and we urgently need to explore new treatment options, such as
cilengitide, in Phase III studies to offer real improvements in
outcomes," commented lead study investigator, Professor Burt
Nabors, Professor of Neurology at the University of Alabama,
Birmingham, USA.

These findings add to existing evidence of cilengitide's
clinical activity and tolerability from previous trials in GBM,
both as a single agent and in combination with
chemoradiotherapy, with only rare incidents of grade 3 or 4
drug-related toxicity.3-9 On the basis of these results,
cilengitide is being investigated further in the Phase III
study, CENTRICa and Phase II study, COREb.

"We are united with the glioblastoma community in exploring
the potential of cilengitide for patients with this devastating
disease and, as part of our overall aim of personalizing cancer
care for all patients, we remain committed to the ongoing
development of cilengitide as a combination therapy in GBM and
other cancer types," said Dr Wolfgang Wein, Executive Vice
President, Oncology, Merck KGaA.

Cilengitide development program in GBMa. CENTRIC is a Phase
III, multicenter, open-label, controlled study to assess the
efficacy and safety of cilengitide in combination with standard
chemotherapy (temozolomide, or TMZ) plus radiotherapy versus
standard chemotherapy plus radiotherapy alone, in a specific
subgroup of newly diagnosed patients with GBM. Patients
recruited into the CENTRIC trial will have their tumor tissue
assessed for methylation of the MGMT (methylguanine-DNA
methyltransferase) gene promoter. This gene promoter acts as a
controlling element in the expression of MGMT, an enzyme which
reduces the efficacy of the chemotherapy. The CENTRIC trial is
being conducted in collaboration with the European Organisation
for Research and Treatment of Cancer (EORTC) and the Canadian
Brain Tumour Consortium (CBTC).

b. CORE is an exploratory companion trial to CENTRIC
evaluating cilengitide in GBM patients with unmethylated MGMT
status. CORE is a Phase II, multicenter, open-label study
investigating two cilengitide regimens in combination with
standard treatment (temozolomide with concomitant radiotherapy,
followed by temozolomide maintenance therapy).

Burden of disease

Every year, there are 189,000 new cases of cancer of the
brain and nervous system globally and 142,000 deaths10 GBM is
the most aggressive form of primary brain tumor. Despite
advances in imaging techniques and currently best available
treatments, more than 70% of patients die within 2 years7 For
more information on these studies log on to
www.clinicaltrials.gov.

References 1. Nabors LB, et al. ASCO Congress 2009; Abstract
No: 2001. Updated information presented at meeting.

2. Stupp R, et al. N Engl J Med 2005;352:987-96.

3. Stupp R, et al. ASCO Annual Meeting 2007; Abstract No:
2000.

4. Reardon DA, et al. J Clin Oncol 2008;26(34):5610-7.

5. Nabors LB, et al. J Clin Oncol 2007;25(13):1651-7.

6. MacDonald TJ, et al. J Clin Oncol 2008;26(6):919-24.

7. Reardon DA, et al. Expert Opin Investig Drugs
2008;17(8):1225-35.

8. Stupp R, et al. J Clin Oncol 2007;25(13):1637-8.

9. Gilbert M, et al. SNO Annual Meeting 2007; Abstract No:
MA-39.

10. Parkin DM, et al. CA Cancer J Clin 2005;55:74-108.

About cilengitide

Cilengitide is currently being developed by Merck KGaA.
Cilengitide is the first in a new class of investigational
anti-cancer therapies called integrin inhibitors to reach Phase
III of development; it is currently being investigated for the
treatment of glioblastoma, SCCHN and NSCLC.

Integrin inhibitors are thought to work by targeting the
tumor and its vasculature.

Integrins are cell surface receptors that are improperly
regulated in many cancer types. This lack of regulation enables
them to enhance tumor growth, survival and invasiveness.
Integrins are fundamental in the process of angiogenesis (blood
vessel growth) - a process that is essential for tumors as it
enables them to grow past a finite size.

In addition to the Merck-sponsored studies, the U.S.
National Cancer Institute (NCI) is sponsoring a number of
clinical trials under a Cooperative Research and Development
Agreement (CRADA) with Merck KGaA for the development of
cilengitide.

About Merck

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Merck is a global pharmaceutical and chemical company with
total revenues of $7.6 billion in 2008, a history that began in
1668, and a future shaped by 32,700 employees in 60 countries.
Its success is characterized by innovations from
entrepreneurial employees. Merck's operating activities come
under the umbrella of Merck KGaA, in which the Merck family
holds an approximately 70% interest and free shareholders own
the remaining approximately 30%. In 1917 the U.S. subsidiary
Merck & Co. was expropriated and has been an independent
company ever since.

For Merck KGaA

Dr. Raphaela Farrenkopf,

+49 6151-72 2274

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