Merck Announces FDA Orphan Drug Designation for Bifunctional Immunotherapy M7824 in Biliary Tract Cancer

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DARMSTADT, Germany, December 10, 2018, /PRNewswire=KYODO JBN/--

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    - FDA grants M7824, an investigational bifunctional immunotherapy, orphan

drug designation in biliary tract cancer  

    - First regulatory designation for M7824 following recent presentation of

first clinical data in BTC   

    - BTC is a group of rare, aggressive gastrointestinal cancers associated

with limited treatment options and poor outcomes

    Merck, a leading science and technology company, today announced that the

US Food and Drug Administration (FDA) has granted orphan drug designation (ODD)

to M7824, the first regulatory designation for the bifunctional immunotherapy,

for the treatment of biliary tract cancer (BTC). The FDA orphan drug

designation follows the recent presentation of the first clinical data for

M7824 in BTC at the European Society of Medical Oncology (ESMO) congress in

October. M7824 is an investigational bifunctional immunotherapy designed to

combine co-localized blocking of the transforming growth factor-beta and

anti-PD-L1 immune escape mechanisms.

    BTC is a collective term for a group of rare and aggressive

gastrointestinal cancers, including intrahepatic cholangiocarcinoma (ICC),

extrahepatic cholangiocarcinoma (ECC), and gallbladder carcinoma (GBC).[1]

Approximately 16,000 cases of BTC are estimated to occur every year in the US

and collectively these cancers present late in the majority of patients.[1],[2]

Treatment options are limited and the median survival rate in the advanced

setting is less than one year, objective tumor response with commonly used

chemotherapy is typically less than 10% with short duration of

response.[1],[3],[5]

    "Biliary tract cancer is a rare, notoriously hard-to-treat tumor where

existing treatment approaches, such as surgery or chemotherapy, are either not

viable or simply don't deliver acceptable patient outcomes," said Luciano

Rossetti, Head of Global Research & Development at the Biopharma business of

Merck. "As the first regulatory designation for M7824, Merck is excited about

the potential of this new class of immunotherapy in a number of challenging

cancers and settings."

    The first clinical data for M7824 in BTC, presented at the ESMO congress in

October, demonstrated clinical activity in Asian patients who had progressed

after platinum-based first-line treatment. The ORR among the total of 30

patients was 20%, as assessed by IRC, and responses were observed across PD-L1

levels with a duration of response ranging from 8.3 months to 13.9+ months.

Grade 3 or higher TRAEs were experienced by 10 patients (33.3%)  and the most

common Grade 3 TRAEs were rash (10%) and lipase increase (10%).

    FDA Orphan Drug Designation (ODD) is granted to medicines intended to treat

rare diseases or disorders that affect fewer than 200,000 people in the US, or

those that affect more than 200,000 people but are unlikely to recover the

costs of developing and marketing the drug. Medicines that meet the FDA's ODD

criteria qualify for a number of incentives to help support advancement.

    M7824 is an investigational bifunctional immunotherapy that combines a

TGF-beta trap with the anti-PD-L1 mechanism in one fusion protein. Designed to

combine co-localized blocking of the two immunosuppressive pathways, M7824 is

thought to control tumor growth by potentially restoring and enhancing

anti-tumor responses. M7824 is an important part of a novel combination

approach that seeks to harness the power of the immune system and address the

tremendously complex nature of difficult-to-treat tumors. To-date, more than

670 patients with various types of solid tumors have been treated across the

program with M7824. In addition to BTC, M7824 is being studied in solid tumor

indications, including non-small cell lung, HPV associated tumors and

gastrointestinal cancers, such as gastric cancer, esophageal squamous cell

carcinoma and esophageal adenocarcinoma.

    About M7824

    M7824 is an investigational bifunctional immunotherapy that is designed to

combine a TGF-beta trap with the anti-PD-L1 mechanism in one fusion protein.

M7824 is designed to combine co-localized blocking of the two immunosuppressive

pathways - targeting both pathways aims to control tumor growth by potentially

restoring and enhancing anti-tumor responses. M7824 is currently in Phase I

studies for solid tumors, as well as a trial to investigate M7824 compared with

pembrolizumab as a first-line treatment in patients with PD-L1 expressing

advanced NSCLC. The multicenter, randomized, open-label, controlled study is

evaluating the safety and efficacy of M7824 versus pembrolizumab as a

monotherapy treatment.

    About the FDA Orphan Designation

    FDA orphan drug designation is granted to drugs intended to treat rare

diseases or disorders that affect fewer than 200,000 people in the US, or those

that affect more than 200,000 people, but are unlikely to recover the costs of

developing and marketing the drug. Orphan drug designation by the FDA qualifies

the sponsor for incentives provided for in the Orphan Drug Act, which can

include protocol assistance for clinical trials, prescription drug user fee

waivers, tax incentives and seven years of market exclusivity. The granting of

an orphan drug designation does not alter the standard regulatory requirement

to establish the safety and effectiveness of a drug through adequate and

well-controlled studies to support approval. The orphan drug designation for

M7824 applies only to BTC.

    About Biliary Tract Cancer (BTC)

    BTC is a collective term for a group of rare and aggressive

gastrointestinal cancers, including intrahepatic cholangiocarcinoma (iCC),

extrahepatic cholangiocarcinoma (eCC), and gallbladder carcinoma (GBC).[1]

Surgery is the only curative treatment, but most patients present with advanced

disease and therefore have a limited survival.[1]  Approximately 140,000 cases

of BTC are estimated to occur annually world-wide.[2] However,  incidence of

BTC varies in different parts of the world: the incidence of

cholangiocarcinomas is rising in the Western world, with reports of up to 2 in

100,000[4]. By contrast, in Asian countries, the incidence is much higher.[4]

GBC also has an incidence of 2 in 100,000, but is much more prevalent in

parts of South America.[4] Collectively these cancers present late in the

majority of patients and long-term outcomes for resectable patients are poor

with median survival in the advanced setting less than 1 year.[1],[3]

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    About Merck

    Merck, a vibrant science and technology company, operates across

healthcare, life science and performance materials. Around 51,000 employees

work to make a positive difference to millions of people's lives every day by

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    Scientific exploration and responsible entrepreneurship have been key to

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    References

    1) Blair A B et al. Immunotherapy as a treatment for biliary tract cancers:

A review of approaches with an eye to the future. Current Problems in Cancer

(2018)

https://www.sciencedirect.com/science/article/pii/S0147027217301083?via%3Dihub

Accessed November 2018     

    2) Global Burden of Disease Study 2013. The Lancet

2015;385(9963):117-171.     

    3) Hezel AF et al. Genetics of biliary tract cancers and emerging targeted

therapies. J Clin Oncol 2010;28:3531-40.

http://dx.doi.org/10.1200/JCO.2009.27.4787  Accessed November 2018     

    4) Goldstein D et al. New molecular and immunotherapeutic approaches in

biliary cancer. ESMO Open (2017). Published online 2017 Mar 27. doi:

https://dx.doi.org/10.1136%2Fesmoopen-2016-000152 Accessed November 2018     

    5) Lamarca A, et al. Ann Oncol. 2014;25(12):2328-2338.

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