Merck Agrees to Return Kuvan(R) Rights to BioMarin Pharmaceutical to Strengthen Focus on Core Business

PR62020

DARMSTADT, Germany, Oct. 1, 2015 /PRNewswire=KYODO JBN/ --

    - Agreement with BioMarin, a leading company in the treatment of genetic

and rare diseases, also includes returning option to develop and commercialize

Peg-Pal

     - Merck to receive upfront payment of EUR 340 million, plus up to

EUR 185  million in additional milestones

    Merck, a leading company for innovative and top-quality high-tech products

in healthcare, life science and performance materials, today announced that it

has reached an agreement with BioMarin Pharmaceutical, Inc., San Rafael,

California, U.S., to return the rights to Kuvan(R), used to treat

phenylketonuria (PKU), a rare metabolism disorder, as the company focuses its

healthcare business on core areas.

    In addition to Kuvan(R), the two companies agreed that Merck will return

its option to develop and commercialize Peg-Pal, an investigational drug that

is also designed for the treatment of PKU, an autosomal recessive genetic

disorder caused by either a defect or a deficiency of the enzyme phenylalanine

hydroxylase or its co-factor tetrahydrobiopterin. Merck will receive an upfront

payment of EUR 340 million, equal to five times its annual sales, for Kuvan(R),

plus up to EUR 185 million in additional milestones for both products. The

agreement is expected to become effective Jan. 1, 2016.

    "Returning the rights of Kuvan(R) and Peg-Pal to BioMarin will allow Merck

to fully focus on its core businesses, as well as further align R&D investment

behind key strategic areas," said Belen Garijo, Member of the Executive Board

of Merck and CEO Healthcare. "Patients suffering from PKU will continue to

benefit from these therapeutic options, as well as from BioMarin's long-term

expertise in rare diseases."

    Merck remains highly committed to the patients in the field of

endocrinology, and in particular to advancing the treatment of growth hormone

deficient patients with Saizen(R).

    Over the past years, Merck has re-aligned its healthcare business with a

special focus on developing novel therapies in the areas of neurology,

oncology, immuno-oncology and immunology, in addition to maximizing its

existing portfolio of drugs in developed countries as well as expanding its

footprint in Emerging Markets.

    Merck had acquired the rights for Kuvan(R) and the option to Peg-Pal in

markets outside of the U.S. and Japan from BioMarin in 2005.* Since launching

Kuvan(R) as a treatment alternative to diet alone, which constituted a paradigm

shift at the time, Merck has significantly contributed to improving PKU

management. More recently, Merck's SPARK study helped pave the way for the

treatment of infants with PKU below 4 years of age with Kuvan(R). By returning

the rights to BioMarin, Merck is confident that the product will continue to

serve the best interest of the medical community and patients. A leading

company in the treatment of genetic and rare diseases, BioMarin is dedicated to

improving the treatment options and to providing all resources needed to

continue to make Kuvan(R) available, as well as to explore potential future

therapies in this area, such as Peg-Pal. Merck will work closely with BioMarin

during the transition to ensure continuous access to Kuvan(R) for patients,

physicians and health authorities.

    Kuvan(R) is indicated for the treatment of hyperphenylalaninemia (HPA) due

to PKU in patients of all ages who have shown to be responsive to Kuvan(R), or

due to tetrahydrobiopterin (BH4) deficiency.

    In a conference call later today, (October 1, 2015, 14:00 CEST) Merck

management discusses key focus areas on its healthcare pipeline in

immune-oncology, oncology and immunology (the call can be followed live here

[http://edge.media-server.com/m/p/5i9jg9t3 ] ).

    * Merck Serono also acquired the rights to Kuvan(R) in Canada as a part of

this original agreement in 2005, but returned those rights in 2007.

    About phenylketonuria (PKU)

    PKU is an autosomal recessive genetic disorder caused by a defect or a

deficiency of the enzyme phenylalanine hydroxylase (PAH) or its cofactor

tetrahydrobiopterin (BH4). PAH is required for the metabolism of phenylalanine,

an essential amino acid found in all protein-containing foods. It affects

approximately 1/10,000 newborns in Europe. If PKU patients are not treated with

a phenylalanine-restricted diet, phenylalanine will accumulate in the blood and

brain to abnormally high levels, thereby resulting in a variety of

complications including mental retardation and brain damage, mental illness,

seizures and tremors, and clinically significant cognitive problems. Universal

systematic newborn screening programs were developed in the 1960s and early

1970s to enable diagnosis of all patients with PKU patients at birth.

    About Kuvan(R)

    Kuvan(R) (sapropterin dihydrochloride) is the first oral therapy and

approved for the treatment of hyperphenylalaninemia (HPA) due to

phenylketonuria (PKU) in patients of all age who have shown to be responsive to

Kuvan(R) or due to tetrahydrobiopterin (BH4) deficiency(R). Kuvan(R) was

developed jointly by BioMarin Pharmaceutical Inc. and Merck Serono. Kuvan(R) is

to be used in conjunction with a phenylalanine-restricted diet.

    Kuvan(R) is the synthetic form of 6R-BH4, a naturally occurring co-factor

that works in conjunction with the enzyme phenylalanine hydroxylase (PAH) to

metabolize phenylalanine into tyrosine. Clinical data show that Kuvan(R)

produces significant reductions in blood phenylalanine concentration in a large

subset of patients.

    Most common adverse reactions reported with the use of Kuvan(R) include

headache, rhinorrhea, pharyngolaryngeal pain, nasal congestion, cough,

diarrhea, vomiting, abdominal pain, and low levels of phenylalanine in the

blood.

    Kuvan(R) is approved in 51 countries worldwide, including member states of

the European Union and the USA. Under the terms of the former agreement with

BioMarin, Merck Serono had received exclusive rights to market Kuvan(R) in all

territories outside the USA,  Canada and Japan, all these rights have now been

returned to BioMarin.

    About Peg-Pal

    PEG-PAL (PEGylated recombinant phenylalanine ammonia lyase or 'PAL',

pegvaliase) is an investigational drug that substitutes for the PAH enzyme in

phenylketonuria (PKU). PEG-PAL is being developed as a potential treatment for

patients whose blood phenylalanine levels are not adequately controlled by

Kuvan(R) or who have trouble controlling and maintaining their phenylalanine

levels).

    About BioMarin

    BioMarin is a global biotechnology company that develops and commercializes

innovative therapies for patients with serious and life-threatening rare and

ultra-rare genetic diseases. The company's portfolio consists of five

commercialized products and multiple clinical and pre-clinical product

candidates.

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    Merck is a leading company for innovative and top-quality high-tech

products in healthcare, life science and performance materials. The company has

six businesses - Merck Serono, Consumer Health, Allergopharma, Biosimilars,

Merck Millipore and Performance Materials - and generated sales of EUR 11.3

billion in 2014. Around 39,000 employees work for Merck in 66 countries to

improve the quality of life for patients, to foster the success of customers,

and to help meet global challenges. Merck is the world's oldest pharmaceutical

and chemical company - since 1668, the company has stood for innovation,

business success and responsible entrepreneurship. Holding an approximately 70%

interest, the founding family remains the majority owner of the company to this

day. Merck, Darmstadt, Germany holds the global rights to the Merck name and

brand. The only exceptions are Canada and the United States, where the company

operates as EMD Serono, EMD Millipore and EMD Performance Materials.

Source: Merk