LEIDEN, The Netherlands,
July 18, 2016 /PRNewswire/ --
RUCONEST® showed
clinically and statistically significant
reduction in attack frequency both in
twice weekly and once- weekly dosing
Pharming Group N.V. ("Pharming" or "the Company") (EURONEXT:
PHARM) today announced positive results from a Phase 2 clinical
study of RUCONEST® (recombinant C1 esterase inhibitor, 50 IU/kg)
for prophylaxis in patients with hereditary angioedema (HAE).
In the study, RUCONEST® showed a clinically relevant and
statistically significant reduction in attack frequency for both
the twice-weekly and once-weekly treatment regimens as compared
with placebo.
Thirty-two HAE patients deficient in C1 esterase inhibitor and
with a history of at least four attacks per month were enrolled in
the randomized, double-blind, placebo-controlled study. The
patients received RUCONEST® once and twice weekly and placebo in
each of three four-week treatment periods in a cross-over design.
The primary efficacy endpoint was the number of HAE attacks per 28
day treatment period and the secondary endpoint was clinical
response, defined as a ≥ 50% reduction in the number of attacks
from treatment with placebo to treatment with RUCONEST®.
In the intent-to-treat analysis (ITT), the study found a
statistically significant difference in the mean number of HAE
attacks that patients experienced during treatment with both the
twice-weekly (p-value <0.0001) and once-weekly (p-value
=0.0004) RUCONEST® regimen as compared with placebo.
Patients on placebo had a mean of 7.2 attacks (95% confidence
interval[CI]: 5.8-8.6) per four week treatment period which was
reduced to a mean of 2.7 attacks on RUCONEST® twice weekly (95% CI:
1.8-3.7) and a mean of 4.4 attacks on RUCONEST® once-weekly (95%
CI: 3.1-5.6).
For the analysis of the secondary endpoint in the ITT
population, 74% of patients (95% CI: 57-86) on the twice-weekly
RUCONEST® regimen had at least a 50% reduction in their attack
frequency.
This was confirmed in the per-protocol population of patients,
which included patients who completed the study without any major
deviations (n=23), where 96% of patients (95% CI: 79-99) on the
twice-weekly RUCONEST® regimen and 57% (95%CI: 37-74) on the once
weekly RUCONEST® regimen had at least a 50% reduction in their
attack frequency. Furthermore, in this group, twice weekly
RUCONEST® treatment reduced the attack frequency by 72% (95% CI:
63-81) and once weekly RUCONEST® treatment reduced attack
frequency by 44% (95% CI: 27-62) as compared with
placebo.
RUCONEST® was generally well-tolerated in the study. No
patients withdrew from the study due to adverse events. There
were no related serious adverse events. There were no thrombotic or
thromboembolic events observed. There were no
hypersensitivity or anaphylactic reactions. There were also
no neutralizing antibodies detected.
Marc Riedl, Professor of Medicine
and Clinical Director of the US HAEA Angioedema Center at UCSD and
co-prinicipal investigator for the study, commented: "The results
of this well-controlled prophylactic study demonstrate a clinically
relevant reduction of HAE attack frequency and a high responder
rate with the recombinant C1INH treatment. Combined with the
excellent safety profile, this data supports further development of
recombinant C1INH as a useful preventive therapy for
HAE."
Marco Cicardi, Professor of
Internal Medicine University of Milan, Hospital L. Sacco Milan and co-prinicipal investigator for the
study, remarked: "The clinical efficacy and responder rate in this
well-controlled study clearly indicate that, despite its short half
life, recombinant C1-inhibitor has the potential to become a
prophylactic treatment for HAE. The results also mark an important
step forward to further understanding the underlying mode of action
of C1-inhibitor therapy in the treatment of HAE."
Prof. Dr. Bruno Giannetti,
Pharming's COO, added: "We are very encouraged by these results and
now look forward to reviewing the results with the FDA and EMA to
be able to determine how to bring RUCONEST®, as the first and only
recombinant C1- inhibitor, to patients who need prophylactic
treatment for their HAE."
Under the terms of the North American licensing agreement with
Valeant Pharmaceuticals International, Valeant and Pharming share
50/50 the development costs for RUCONEST® for prophylaxis of HAE.
Pharming will receive an undisclosed milestone payment from Valeant
as and when FDA approval for this additional indication is given.
RUCONEST® has been granted Orphan Drug designation by FDA for the
prophylactic treatment of angioedema caused by hereditary or
acquired C1 esterase inhibitor deficiency, with data exclusivity
until 2026 under the Biologics Price Competition and Innovation
Act.
Important Safety Information for
RUCONEST®
Indication
RUCONEST® is a recombinant C1 esterase inhibitor
indicated for the treatment of acute attacks in adult and
adolescent patients with hereditary angioedema (HAE). Effectiveness
in clinical studies was not established in HAE patients with
laryngeal attacks.
RUCONEST (C1 esterase inhibitor [recombinant]) is
contraindicated in patients with a history of allergy to rabbits or
rabbit-derived products, and patients with a history of
life-threatening immediate hypersensitivity reactions to C1
esterase inhibitor preparations, including anaphylaxis.
Severe hypersensitivity reactions may occur. The signs and
symptoms of hypersensitivity reactions may include hives,
generalized urticaria, tightness of the chest, wheezing,
hypotension, and/or anaphylaxis during or after injection of
RUCONEST. Should symptoms occur, discontinue RUCONEST and
administer appropriate treatment. Because hypersensitivity
reactions may have symptoms similar to HAE attacks, treatment
methods should be carefully considered.
Serious arterial and venous thromboembolic (TE) events have been
reported at the recommended dose of plasma-derived C1 esterase
inhibitor products in patients with risk factors. Risk factors may
include the presence of an implanted venous catheter/access device,
prior history of thrombosis, underlying atherosclerosis, use of
oral contraceptives or certain androgens, morbid obesity, and
immobility. Monitor patients with known risk factors for TE
events during and after RUCONEST administration.
RUCONEST has not been studied in pregnant women; therefore, it
should only be used during pregnancy if clearly needed.
The most common adverse reactions (incidence ≥2%) were headache,
nausea, and diarrhea. The serious adverse reaction in clinical
studies of RUCONEST was anaphylaxis.
Please see complete Prescribing Information for
RUCONEST.
About RUCONEST®
RUCONEST® (recombinant C1 esterase inhibitor ) is indicated for
the treatment of acute attacks in adult and adolescent patients
with hereditary angioedema (HAE). Effectiveness in clinical studies
was not established in HAE patients with laryngeal attacks.
HAE is caused by a deficiency of the C1 esterase inhibitor
protein, which is present in blood and helps control inflammation
(swelling) and parts of the immune system. A shortage of C1
esterase inhibitor can lead to repeated attacks of swelling, pain
in the abdomen, difficulty breathing and other symptoms. RUCONEST
contains C1 esterase inhibitor at 50 IU/kg.
When administered at the onset of HAE attack symptoms at the
recommended dose, RUCONEST may help to return a patient's C1
esterase inhibitor levels to normal range and relieve the symptoms
of an HAE attack with a low recurrence of symptoms within 24
hours.
RUCONEST is the only recombinant C1 esterase inhibitor approved
by the U.S. Food and Drug Administration (FDA) and was approved in
July 2014.
Under the Biologics Price Competition and Innovation Act of
2009, RUCONEST was granted Market exclusivity in the USA until July
2026
RUCONEST is designated as an orphan drug by the FDA for the
treatment of acute attacks of angioedema caused by hereditary or
acquired C1 esterase inhibitor deficiency.
About HAE
Hereditary Angioedema (HAE) is a rare genetic disorder. It is
characterised by spontaneous and recurrent episodes of swelling
(edema attacks) of the skin in different parts of the body, as well
as in the airways and internal organs. Edema of the skin usually
affects the extremities, the face, and the genitals. Patients
suffering from this kind of edema often withdraw from their social
lives because of the disfiguration, discomfort and pain these
symptoms may cause. Almost all HAE patients suffer from bouts of
severe abdominal pain, nausea, vomiting and diarrhea caused by
swelling of the intestinal wall.
Edema of the throat, nose or tongue is particularly dangerous
and potentially life-threatening and can lead to obstruction of the
airway passages. Although there is currently no known cure for HAE,
it is possible to treat the symptoms associated with edema attacks.
HAE affects about 1 in 10,000 to 1 in 50,000 people worldwide.
Experts believe that a lot of patients are still seeking the right
diagnosis: although HAE is (in principle) easy to diagnose, it is
frequently identified very late or not discovered at all. The
reason HAE is often misdiagnosed is because the symptoms are
similar to those of many other common conditions such as allergies
or appendicitis. By the time it is diagnosed correctly, the patient
has often been through a long-lasting ordeal.
About Pharming Group NV
Pharming is a specialty pharmaceutical company developing
innovative products for the safe, effective treatment of rare
diseases and unmet medical needs. Pharming's lead product,
RUCONEST® (conestat alfa) is a recombinant human C1 esterase
inhibitor approved for the treatment of acute Hereditary Angioedema
("HAE") attacks in patients in Europe, the US and rest of the world. The
product is available on a named-patient basis in other territories
where it has not yet obtained marketing authorization.
RUCONEST® is commercialized by Pharming in Austria, Germany and The
Netherlands.
RUCONEST® is distributed by Swedish Orphan Biovitrum AB (publ)
(SS: SOBI) in the other EU countries, and in Azerbaijan, Belarus, Georgia, Iceland, Kazakhstan, Liechtenstein, Norway, Russia, Serbia, and Ukraine.
RUCONEST® is distributed in North
America, Canada and
Mexico by Valeant Pharmaceuticals
International, Inc. (NYSE: VRX/TSX: VRX), following Valeant's
acquisition of Salix Pharmaceuticals, Ltd.
RUCONEST® is distributed in Argentina, Colombia, Costa
Rica, the Dominican
Republic, Panama and
Venezuela, by Cytobioteck.
RUCONEST® is distributed in South
Korea by HyupJin Corporation and in Israel by Megapharm.
RUCONEST® is being investigated in a Phase II randomized, double
blind placebo-controlled clinical trial for prophylactic treatment
of HAE and is being evaluated for other indications as well.
RUCONEST® is also being investigated in a Phase II clinical
trial for the treatment of HAE in young children (2-13 years of
age) and evaluated for various additional follow-on
indications.
Pharming's technology platform includes a unique, GMP-compliant,
validated process for the production of pure recombinant human
proteins that has proven capable of producing industrial quantities
of high quality recombinant human proteins in a more economical and
less immunogenetic way compared with current cell-line based
methods. Leads for enzyme replacement therapy ("ERT") for Pompe and
Fabry's diseases are being optimized at present, with additional
programs not involving ERT also at an early stage of
development.
Pharming has a long term partnership with the Shanghai Institute
of Pharmaceutical Industry ("SIPI"), a Sinopharm company, for joint
global development of new products, starting with recombinant human
Factor VIII for the treatment of Haemophilia A. Pre-clinical
development and manufacturing will take place to global standards
at SIPI and are funded by SIPI. Clinical development will be shared
between the partners with each partner taking the costs for their
territories under the partnership.
Pharming has declared that the
Netherlands is its "Home Member State" pursuant to the
amended article 5:25a paragraph 2 of the Dutch Financial
Supervision Act.
Additional information is available on the Pharming website:
http://www.pharming.com
Forward-looking statements
This press release of Pharming Group N.V. and its subsidiaries
("Pharming", the "Company" or the "Group") may contain
forward-looking statements including without limitation those
regarding Pharming's financial projections, market expectations,
developments, partnerships, plans, strategies and capital
expenditures.
The Company cautions that such forward-looking statements may
involve certain risks and uncertainties, and actual results may
differ. Risks and uncertainties include without limitation the
effect of competitive, political and economic factors, legal
claims, the Company's ability to protect intellectual property,
fluctuations in exchange and interest rates, changes in taxation
laws or rates, changes in legislation or accountancy practices and
the Company's ability to identify, develop and successfully
commercialise new products, markets or technologies.
As a result, the Company's actual performance, position and
financial results and statements may differ materially from the
plans, goals and expectations set forth in such forward-looking
statements. The Company assumes no obligation to update any
forward-looking statements or information, which should be taken as
of their respective dates of issue, unless required by laws or
regulations.
Contacts:
Sijmen de Vries, CEO: T: +31-71-524-7400
FTI Consulting: Julia
Phillips/ Victoria Foster
Mitchell, T: +44-203-727-1136
PRN NLD