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KUVAN™ (sapropterin
DIhydrochloride) for PKU
Kuvan™ (sapropterin
dihydrohchloride), formerly known as Phenoptin™,
is the first FDA-approved treatment for phenylketonuria
(PKU), an inherited metabolic disease caused by
a deficiency of the enzyme phenylalanine hydroxylase
(PAH). Insufficient quantities or reduced activity
of PAH results in elevated levels of phenylalanine
(Phe) in the blood. Sustained elevated blood Phe
levels can result in serious neurological damage.
| Kuvan
at a Glance |
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Approved
by the FDA in December 2007 |
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Designated
orphan drug status in the United States
and European Union; Granted Fast Track
status in the United States |
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BioMarin partner
Merck Serono, a division of Merck KGaA,
Darmstadt, Germany, submitted a Marketing
Authorization Application (MAA) to the
European Medicines Agency (EMEA) in
November 2007. |
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Sapropterin dihydrochloride, the active ingredient
in Kuvan, is a synthetic form of 6R-BH4. 6R-BH4
is an essential enzyme cofactor that works in conjunction
with PAH to metabolize Phe.
Nearly all developed countries test for PKU as part
of their newborn screening program. An estimated
50,000 people under 40 years of age are living with
the disease in developed countries.
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On March 15, 2006, BioMarin and Serono announced
positive results from a Phase 3, double-blind,
placebo-controlled, multi-center clinical study
designed to evaluate the safety and efficacy of
Kuvan. The study enrolled 89 patients with
elevated blood Phe levels aged eight years and
above at 29 sites in the United States, Europe
and Canada. All patients had demonstrated a reduction
in blood Phe levels (approximately 30 percent
or more) following treatment with Phenoptin in
a Phase 2 screening study.
Patients were randomly assigned to receive placebo
or 10 mg/kg of Kuvan daily for six weeks and
were evaluated every two weeks for changes in
blood Phe levels and adverse events. The primary
endpoint of the study was the difference in mean
blood Phe levels between the placebo and Kuvan
groups at Week 6, adjusted for baseline levels.
A total of 87 patients completed six weeks of
treatment.
Results confirm that all pre-specified primary and
secondary endpoints were met and data from the Phase
3 study demonstrate a statistically significant
reduction at six weeks in blood phenylalanine (Phe)
levels (p<0.0001) in patients receiving Kuvan,
compared with those receiving placebo. The type
and incidence of adverse events was similar in the
Kuvan and placebo groups. The most frequent
adverse events occurred in the Infections and Infestations
and Gastrointestinal Disorders system organ classes.
Kuvan was well tolerated and investigators reported
that no serious adverse event occurred. |
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The 22-week Phase 3 open-label
extension study was designed to further evaluate the
long-term safety and efficacy of Kuvan, as well
as dose titration. Kuvan demonstrated an excellent safety and tolerability profile for all three doses and provided a dose-dependent reduction in blood Phe levels relative to baseline.
Additionally, results from the Phase 3 diet study demonstrated that Kuvan treatment caused a significant increase in Phe tolerance, a reduction in blood Phe levels, and was well-tolerated in patients ages 4-12 years under dietary control.
Kuvan received orphan drug designation to
treat PKU from both the U.S. Food and Drug Administration
(FDA) and European Medicines Agency (EMEA). If
Kuvan becomes the first drug therapy approved
for the treatment of PKU, it 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
Kuvan Fast Track designation, which is designed
to facilitate the development and review of new
drugs that are intended to treat serious or life-threatening
conditions and that demonstrate the potential
to address unmet medical needs.
BioMarin plans to file a New Drug Application in the second quarter of 2007.
BioMarin is developing Kuvan in partnership
with Merck Serono, pursuant to a partnership formed in
May 2005. To learn more about this partnership,
please visit the 'Business/Partnerships' section
of this website.
The data referenced in the preceding paragraphs represent the most recently announced data pertaining to this program. For data from earlier trials, please refer to the press release section of this website. |
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