Phenoptin Significantly Increases Phenylalanine Tolerance in BH4-Responsive
                 Patients; All Pre-Specified Endpoints Met

    GENEVA, Switzerland, January 16 /PRNewswire-FirstCall/ -- Merck Serono
(virt-x: SEO and NYSE: SRA) today announced positive results from the Phase
III diet study of Phenoptin(TM) (sapropterin dihydrochloride), in
combination with diet, in 4-12 year old patients. Phenoptin is an
investigational oral small molecule, being developed in partnership with
BioMarin, for the treatment of patients with phenylketonuria (PKU), who
have elevated phenylalanine (Phe) levels. The results show that all
pre-specified efficacy and safety endpoints of the double-blind,
placebo-controlled study were met. Phenoptin treatment caused a significant
increase in phenylalanine tolerance as well as a reduction in blood
phenylalanine levels. In addition, the data showed that Phenoptin was well
tolerated in younger PKU patients who were under dietary control.
    Dr. Harvey Levy, Professor of Pediatrics at Harvard Medical School and
Senior Associate in Medicine and Genetics at Children's Hospital Boston,
stated, "This is the first time a controlled study has demonstrated the
potential of tetrahydrobiopterin, or 6R-BH4, to liberalize diet in PKU
patients. If approved, Phenoptin offers patients who respond to BH4 a real
opportunity to relax their diets and the possibility to perhaps reduce or
even eliminate the need for nutritional supplementation from medical food."
    Key findings from the study:
    - In the primary endpoint, Phenoptin enabled a mean increase of 20.9
mg/kg/day in Phe supplementation for those patients on Phenoptin (p<0.001).
Patients treated with Phenoptin were able to, on average, double their
baseline intake. At week 10, they were able to take a mean total Phe intake
of approximately 43.8 mg/kg/day, while maintaining controlled blood Phe
levels. The mean Phe tolerance represents approximately half the amount of
Phe in a normal diet.
    - The two secondary endpoints were also met:
    - Phenoptin provided a mean reduction of 148.5 mmol/L (from a starting
mean of 275.7 mmol/L) in blood Phe level from baseline to week 3 (prior to
Phe supplementation) (p<0.001).
    - At the end of the study, patients on Phenoptin were able to increase
their daily Phe supplement by a mean of 20.9 mg/kg versus a mean of 2.9
mg/kg for placebo patients (p<0.001).
    - The incidence and types of adverse events were similar in both the
placebo and Phenoptin groups and all reported events were mild or moderate
in severity. There were two serious adverse events (one in the Phenoptin
group and one in the placebo group), neither of which were considered
drug-related. The most frequently reported adverse events were headache,
abdominal pain, fatigue, and diarrhea.
    The 11-week multi-center double-blind, placebo controlled Phase 3 study
enrolled 90 patients between the ages of 4 and 12 years, with blood Phe
levels below 480 mmol/L. Patients were screened for responsiveness to
Phenoptin with an open-label one-week treatment at a dose of 20 mg/kg/day
(Part 1). Of the 89 patients who completed Part 1, 50 subjects demonstrated
a blood Phe reduction of at least 30%, and 45 were randomized to Phenoptin
(20 mg/kg/day) or placebo in a 3:1 ratio, and enrolled in the 10-week
double-blind, placebo-controlled portion of the study (Part 2). For the
first three weeks, patients maintained their pre-existing restricted diet
with no supplementation of phenylalanine. Thereafter, every other week,
specific amounts of phenylalanine were added (or removed) to the restricted
diet of each patient according to pre-defined blood phenylalanine levels.
The maximum amount of Phe that could be added to a patient diet during the
study was 50 mg/kg/day.
    BioMarin and Merck Serono remain on track to file the New Drug
Application in the US and Marketing Authorization Application in Europe for
Phenoptin in PKU in the second and third quarters of 2007, respectively.
    About Phenoptin
    Phenoptin is an investigational oral small molecule therapeutic for the
treatment of PKU. The active ingredient in Phenoptin, sapropterin
dihydrochloride, is the synthetic form of 6R-BH4 (tetrahydrobiopterin), a
naturally occurring enzyme cofactor that works in conjunction with
phenylalanine hydroxylase (PAH) to metabolize Phe. Preliminary clinical
data have suggested that Phenoptin has a potential to produce significant
reductions in blood Phe levels in the subset of patients who are
BH4-responsive. BioMarin and Merck Serono estimate that Phenoptin could be
a potential treatment option for approximately 30 percent to 50 percent of
the estimated 50,000 individuals in the developed world who have been
diagnosed with PKU.
    Phenoptin received orphan drug designation to treat PKU from both the
U.S. Food and Drug Administration (FDA) and European Medicines Agency
(EMEA). If Phenoptin becomes the first drug therapy approved for the
treatment of PKU, Phenoptin would receive seven years of market exclusivity
in the United States and 10 years in the European Union for this
indication. Additionally, the FDA has granted Phenoptin Fast Track
designation, which is designed to facilitate the development and expedite
the review of new drugs that are intended to treat serious or
life-threatening conditions and that demonstrate the potential to address
unmet medical needs.
    Under the terms of the agreement with BioMarin, Merck Serono has
exclusive rights to market Phenoptin in all territories outside the United
States and Japan. BioMarin has exclusive rights to market Phenoptin in the
United States.
    About PKU
    PKU, a genetic disorder affecting approximately 50,000 diagnosed
patients in the developed world, is caused by a deficiency of the enzyme
phenylalanine hydroxylase (PAH). PAH is required for the metabolism of
phenylalanine (Phe), an essential amino acid found in most
protein-containing foods. If the active enzyme is not present in sufficient
quantities, Phe accumulates to abnormally high levels in the blood and
brain, resulting in a variety of complications including severe mental
retardation and brain damage, mental illness, seizures and tremors, and
cognitive problems. As a result of global newborn screening efforts
implemented in the 1960s and early 1970s, virtually all PKU patients in
developed countries have been diagnosed at birth. The only treatment
currently available for PKU patients is a highly restrictive and expensive
medical food diet that most patients fail to adhere to the extent needed
for achieving adequate control of blood Phe levels. To learn more about
PKU, please visit http://www.PKU.com. Information on this website is not
incorporated by reference into this press release.
    Positive Results from Phase III Clinical Study of Phenoptin for PKU
    Positive results of a Phase III, double-blind, placebo-controlled
clinical study of Phenoptin (sapropterin dihydrochloride), an
investigational oral small molecule for the treatment of phenylketonuria
(PKU) were reported on March 15, 2006. Results confirmed that all
pre-specified primary and secondary endpoints were met and data
demonstrated a statistically significant reduction at six weeks in blood
phenylalanine (Phe) levels (p<0.0001) in patients receiving Phenoptin,
compared with those receiving placebo.
    Forward-looking statements
    Some of the statements in this press release are forward looking. Such
statements are inherently subject to known and unknown risks, uncertainties
and other factors that may cause actual results, performance or
achievements of Merck Serono S.A. and affiliates to be materially different
from those expected or anticipated in the forward-looking statements.
Forward-looking statements are based on Merck Serono's current expectations
and assumptions, which may be affected by a number of factors, including
those discussed in this press release and more fully described in Serono's
Annual Report on Form 20-F filed with the U.S. Securities and Exchange
Commission on February 28, 2006. These factors include any failure or delay
in Merck Serono's ability to develop new products, any failure to receive
anticipated regulatory approvals, any problems in commercializing current
products as a result of competition or other factors, our ability to obtain
reimbursement coverage for our products, the outcome of any government
investigations and litigation. Merck Serono is providing this information
as of the date of this press release, and has no responsibility to update
the forward-looking statements contained in this press release to reflect
events or circumstances occurring after the date of this press release.
    About Merck Serono
    Merck Serono is a global biotechnology leader, with sales in over 90
countries. The Company is the world leader in reproductive health, with
Gonal-f(R), Luveris(R) and Ovidrel(R)/Ovitrelle(R). It has strong market
positions in neurology, with Rebif(R), as well as in metabolism and growth,
with Saizen(R), Serostim(R) and Zorbtive(TM). The Company has recently
entered the psoriasis area with Raptiva(R). Merck Serono's research
programs are focused on growing these businesses and on establishing new
therapeutic areas, including oncology and autoimmune diseases.
    Bearer shares of Merck Serono S.A., the holding company, are traded on
the virt-x (SEO) and its American Depositary Shares are traded on the New
York Stock Exchange (SRA).
    About Merck
    Merck is a global pharmaceutical and chemical company with sales of EUR
5.9 billion in 2005, a history that began in 1668, and a future shaped by
about 35,000 employees (including Merck Serono) in 56 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 a 73% interest and free shareholders own the
remaining 27%. In 1917 the U.S. subsidiary Merck & Co. was expropriated and
has been an independent company ever since.

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