https://mb.cision.com/Public/18595/3558558/9674c4639d8d0320_800x800ar.png
** JAMA Neurology Publishes Phase 3 Study Results on the Efficacy and Safet=
y of FINTEPLA^=C2=AE=E2=96=BC(fenfluramine) Oral Solution for the treatment=
of seizures associated with Lennox-Gastaut Syndrome (LGS)
------------------------------------------------------------
=C2=B7 Primary endpoint was met demonstrating that fenfluramine, as adjunct=
ive treatment, is effective in significantly reducing the frequency of drop=
seizures in LGS patients compared to placebo^1
=C2=B7 LGS is a severe childhood-onset developmental and epileptic encephal=
opathy characterized by drug-resistant seizures with high morbidity^2=C2=A0
=C2=B7 Fenfluramine was recently approved by the U.S. Food and Drug Adminis=
tration (FDA), as a treatment option for the treatment of seizures associat=
ed with LGS, a rare and devastating lifelong childhood-onset epilepsy^5
Brussels (Belgium) and Atlanta, GA (USA)., May 2, 2022 =E2=80=93 7:00 PM (C=
EST) =E2=80=93 UCB (Euronext: UCB), a global biopharmaceutical company, tod=
ay announced the publication in JAMA Neurology of its multi-center, double-=
blind, placebo-controlled, parallel-group, randomized Phase 3 trial demonst=
rating that fenfluramine 0.7 mg/kg/day, when added to a patient=E2=80=99s c=
urrent anti-epileptic treatment regimen for seizures associated with LGS, i=
s effective in reducing the frequency of drop seizures.^1 Drop seizures cau=
se a person to suddenly lose muscle tone, become limp, and fall to the grou=
nd, with a high likelihood of injury.^6 Within the study, drop seizures wer=
e further defined as generalized tonic-clonic (GTC), secondary GTC [focal t=
o bilateral tonic clonic], tonic, atonic, or tonic and atonic.^1
LGS is a severe childhood-onset developmental and epileptic encephalopathy =
characterized by drug-resistant seizures with high morbidity^2 as well as s=
erious impairment of neurodevelopmental, cognitive and motor functions.^3 L=
GS has far-reaching effects beyond seizures, including issues with communic=
ation, psychiatric symptoms, sleep, behavioral challenges and mobility.^7=
=C2=A0
The trial met its primary efficacy endpoint. Patients taking fenfluramine 0=
.7 mg/kg/day experienced an estimated mean difference in the reduction of d=
rop seizure frequency by 19.9% from placebo (P=3D.001). The median percent =
reduction in the frequency of drop seizures in the 0.7 mg/kg/day group was =
26.5%, compared with 14.2% in the 0.2mg/kg/day group, and 7.6% in patients =
taking placebo (P=3D.09). In key secondary outcomes, the trial demonstrated=
that a greater proportion of patients taking fenfluramine experienced a 50=
% or greater reduction in drop seizure frequency, compared to patients in t=
he placebo group.^1=C2=A0
=E2=80=9COur trial data and the clinical evidence demonstrate the safety an=
d efficacy of fenfluramine for the treatment of seizures associated with LG=
S and especially for patients where generalized tonic-clonic seizures are t=
he predominant seizure type, where there is a greater risk of mortality,=E2=
=80=9D said Kelly Knupp, M.D., MSCS, FAES, Associate Professor, Children=E2=
=80=99s Hospital Colorado, Principal Investigator of the study. =E2=80=9CLG=
S is a highly treatment-resistant developmental and epileptic encephalopath=
y and we need differentiated treatment options, such as fenfluramine, which=
has a unique mechanism of action different from and complementary to curre=
nt seizure medications.=E2=80=9D
The study also included seizure-type subgroup analyses that demonstrated th=
at fenfluramine 0.7mg/kg/day was highly effective in reducing the frequency=
of GTCs in nearly 50% of patients. During the maintenance and titration pe=
riod, patients experienced a decrease in frequency of 45.7% in the fenflura=
mine 0.7mg/kg/day group, a decrease in frequency of 58.2% in the 0.2 mg/kg/=
day fenfluramine group, compared with an increase in frequency of 3.7% in t=
he placebo group (P=3D.001 and P<.001 respectively). The percentage reducti=
on in tonic or atonic seizure frequency was 46.7% in the fenfluramine 0.7mg=
/kg/day group, compared with 6.8% in the placebo group (P=3D.046).^1
The reason these data are compelling is because GTCs are commonly observed =
in patients with LGS.^9 Moreover, GTCs may result in bodily injury.^10,11 S=
udden unexpected death in epilepsy (SUDEP) is a major concern for people li=
ving with LGS and patients with a history of GTCs have an estimated 10-fold=
greater risk of SUDEP.^4
Fenfluramine was generally well-tolerated in this study. The most common tr=
eatment-emergent adverse events included decreased appetite (22%), somnolen=
ce (13%), and fatigue (13%).^1 The fenfluramine safety database includes lo=
ng-term cardiovascular safety data for patients treated for up to three yea=
rs in DS and LGS.^5
=E2=80=9CThis study further validates the importance of fenfluramine as a n=
ew treatment option for seizures associated with LGS, including generalized=
tonic-clonic seizures,=E2=80=9D said Mike Davis, Global Head of Epilepsy, =
UCB. =E2=80=9CThrough our close connection with the LGS community, we know =
the challenges they face go beyond treatment resistant seizures to include =
difficulty with behavior and cognition, and we hope that fenfluramine can p=
rovide relief for people living with LGS.=E2=80=9D=C2=A0
Site investigators and caregivers also rated patients as significantly much=
or very much improved on the Clinical Global Impression of Improvement (CG=
I-I) scale (investigators 26% vs. 20% vs. 6% and caregivers 34% vs. 27% vs.=
5% for 0.7 mg/kg vs. 0.2 mg/kg vs. placebo, respectively).^1=C2=A0
Fenfluramine was approved by the U.S. Food and Drug Administration (FDA) fo=
r the treatment of LGS in patients aged 2 and older in March 2022.^5 Fenflu=
ramine was also approved for the treatment of Dravet Syndrome in patients a=
ged 2 and older in June 2020^5 and by the EU Commission in December 2020 as=
an add-on treatment for seizures associated with Dravet syndrome in patien=
ts aged 2 and older.^12 UCB acquired Zogenix, Inc. and FINTEPLA^=C2=AE on M=
arch 7, 2022. The acquisition is consistent with UCB=E2=80=99s sustainable =
patient value strategy and continued commitment to providing world-leading =
patient value to all people living with epilepsy, with an increasing focus =
on creating value and new solutions that address the unmet needs of people =
with certain specialized or rare types of epilepsy, where few or no options=
exist.
Study Design
The multi-center, double-blind, placebo-controlled, parallel-group, randomi=
zed Phase 3 clinical trial was conducted from 27 November 2017 to 25 Octobe=
r 2019, and had a 20-week trial duration. Patients were enrolled at 65 stud=
y sites in North America, Europe, and Australia.
A total of 263 patients were randomly assigned to receive either fenflurami=
ne 0.7mg/kg/day (n=3D87) or fenfluramine 0.2mg/kg/day (n=3D89) or placebo (=
n=3D87). After titration (2-week period), patients were maintained on their=
randomized dose for 12 additional weeks. The median age was 13 years.
Children and adults, aged 2 to 35 years, with a confirmed LGS diagnosis who=
were using stable anti-seizure medication (ASM) regimens (=E2=89=A51 and =
=E2=89=A44 concomitant ASMs) were eligible for enrollment if these criteria=
were met: onset of seizures at age 11 years or younger; multiple seizure t=
ypes, including tonic and tonic or atonic seizures; stable 4-week seizure b=
aseline with 2 or more drop seizures per week of GTC, or secondary GTC (i.e=
., focal to bilateral tonic-clonic seizures), tonic, atonic, or tonic or at=
onic seizure; abnormal cognitive development; and medical history showing e=
lectroencephalogram evidence of abnormal background activity with slow spik=
e-and-wave pattern (<2.5Hz). Key exclusion criteria were degenerative neuro=
logical disease, history of hemiclonic seizures in the first year of life, =
only drop seizure clusters, previous or current exclusionary cardiovascular=
or cardiopulmonary abnormality or concomitant cannabidiol use (not FDA app=
roved at time of study).
This study was funded by Zogenix, Inc., now part of UCB. =C2=A0
About FINTEPLA^=C2=AE (fenfluramine) C-IV
FINTEPLA^=C2=AE (fenfluramine) oral solution is a prescription medication a=
pproved by the FDA and authorized by the EU Commission, and under regulator=
y review with the PMDA (Japan), for the treatment of seizures associated wi=
th Dravet syndrome in patients two years of age and older.^12,13 FINTEPLA i=
s also approved in the U.S. for the treatment of seizures associated with L=
ennox-Gastaut syndrome.^5 Application has also been submitted and is curren=
tly under assessment by the European Medicines Agency (EMA) for the treatme=
nt of seizures associated with LGS.^14
In the United States, FINTEPLA is available only through a restricted distr=
ibution program called the FINTEPLA REMS program. FINTEPLA is available in =
Europe under a controlled access program requested by the EMA to prevent of=
f-label use for weight management and to confirm that prescribing physician=
s have been informed of the need for periodic cardiac monitoring in patient=
s taking FINTEPLA. Further information is available at www.FinteplaREMS.com=
(http://www.FinteplaREMS.com) or by telephone at +1 877 964 3649.
Please see full Prescribing Information (https://www.zogenix.com/pi/Fintepl=
a-prescribing-information.pdf) , including Boxed Warning, for additional im=
portant information on FINTEPLA.
INDICATIONS AND USAGE
FINTEPLA is indicated for the treatment of seizures associated with Dravet =
syndrome (DS) and Lennox-Gastaut syndrome (LGS) in patients 2 years of age =
and older.
IMPORTANT SAFETY INFORMATION
BOXED WARNING: VALVULAR HEART DISEASE and PULMONARY ARTERIAL HYPERTENSION
=C2=B7 There is an association between serotonergic drugs with 5-HT2B recep=
tor agonist activity, including fenfluramine (the active ingredient in FINT=
EPLA), and valvular heart disease and pulmonary arterial hypertension.
=C2=B7 Echocardiogram assessments are required before, during, and after tr=
eatment with FINTEPLA.
=C2=B7 FINTEPLA is available only through a restricted program called the F=
INTEPLA REMS.
CONTRAINDICATIONS
FINTEPLA is contraindicated in patients with hypersensitivity to fenflurami=
ne or any of the excipients in FINTEPLA and with concomitant use, or within=
14 days of the administration of monoamine oxidase inhibitors because of a=
n increased risk of serotonin syndrome.
WARNINGS AND PRECAUTIONS
Valvular Heart Disease and Pulmonary Arterial Hypertension (see Boxed Warni=
ng): Because of the association between serotonergic drugs with 5=E2=80=93H=
T2B receptor agonist activity, including fenfluramine (the active ingredien=
t in FINTEPLA), and valvular heart disease (VHD) and pulmonary arterial hyp=
ertension (PAH), cardiac monitoring via echocardiogram is required prior to=
starting treatment, during treatment, and after treatment with FINTEPLA co=
ncludes. Cardiac monitoring via echocardiogram can aid in early detection o=
f these conditions. In clinical trials for DS and LGS of up to 3 years in d=
uration, no patient receiving FINTEPLA developed VHD or PAH.
Monitoring: Prior to starting treatment, patients must undergo an echocardi=
ogram to evaluate for VHD and PAH. Echocardiograms should be repeated every=
6 months, and once at 3-6 months post treatment with FINTEPLA.
The prescriber must consider the benefits versus the risks of initiating or=
continuing treatment with FINTEPLA if any of the following signs are obser=
ved via echocardiogram: valvular abnormality or new abnormality; VHD indica=
ted by mild or greater aortic regurgitation or moderate or greater mitral r=
egurgitation, with additional characteristics of VHD (eg, valve thickening =
or restrictive valve motion); PAH indicated by elevated right heart/pulmona=
ry artery pressure (PASP >35mmHg).
FINTEPLA REMS Program (see Boxed Warning): FINTEPLA is available only throu=
gh a restricted distribution program called the FINTEPLA Risk Evaluation an=
d Mitigation Strategy (REMS) Program. Prescribers must be certified by enro=
lling in the FINTEPLA REMS. Prescribers must counsel patients receiving FIN=
TEPLA about the risk of valvular heart disease and pulmonary arterial hyper=
tension, how to recognize signs and symptoms of valvular heart disease and =
pulmonary arterial hypertension, the need for baseline (pretreatment) and p=
eriodic cardiac monitoring via echocardiogram during FINTEPLA treatment, an=
d cardiac monitoring after FINTEPLA treatment. Patients must enroll in the =
FINTEPLA REMS and comply with ongoing monitoring requirements. The pharmacy=
must be certified by enrolling in the FINTEPLA REMS and must only dispense=
to patients who are authorized to receive FINTEPLA. Wholesalers and distri=
butors must only distribute to certified pharmacies. Further information is=
available at www.FinteplaREMS.com or by telephone at 1-877-964-3649.
Decreased Appetite and Decreased Weight: FINTEPLA can cause decreases in ap=
petite and weight. Decreases in weight appear to be dose related. Approxima=
tely half of the patients with LGS and most patients with DS resumed the ex=
pected measured increases in weight during the open-label extension studies=
. Weight should be monitored regularly during treatment with FINTEPLA, and =
dose modifications should be considered if a decrease in weight is observed=
.
Somnolence, Sedation, and Lethargy: FINTEPLA can cause somnolence, sedation=
, and lethargy. Other central nervous system (CNS) depressants, including a=
lcohol, could potentiate these effects of FINTEPLA. Prescribers should moni=
tor patients for somnolence and sedation and should advise patients not to =
drive or operate machinery until they have gained sufficient experience on =
FINTEPLA to gauge whether it adversely affects their ability to drive or op=
erate machinery.
Suicidal Behavior and Ideation: Antiepileptic drugs (AEDs), including FINTE=
PLA, increase the risk of suicidal thoughts or behaviors in patients taking=
these drugs for any indication. Patients treated with an AED for any indic=
ation should be monitored for the emergence or worsening of depression, sui=
cidal thoughts or behaviors, or any unusual changes in mood or behavior.
Anyone considering prescribing FINTEPLA or any other AED must balance the r=
isk of suicidal thoughts or behaviors with the risks of untreated illness. =
Epilepsy and many other illnesses for which AEDs are prescribed are themsel=
ves associated with morbidity and mortality and an increased risk of suicid=
al thoughts and behaviors. Should suicidal thoughts and behaviors emerge du=
ring treatment, consider whether the emergence of these symptoms in any giv=
en patient may be related to the illness being treated.
Withdrawal of Antiepileptic Drugs: As with most AEDs, FINTEPLA should gener=
ally be withdrawn gradually because of the risk of increased seizure freque=
ncy and status epilepticus. If withdrawal is needed because of a serious ad=
verse reaction, rapid discontinuation can be considered.
Serotonin Syndrome: Serotonin syndrome, a potentially life-threatening cond=
ition, may occur with FINTEPLA, particularly during concomitant administrat=
ion of FINTEPLA with other serotonergic drugs, including, but not limited t=
o, selective serotonin-norepinephrine reuptake inhibitors (SNRIs), selectiv=
e serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants (TCAs), =
bupropion, triptans, dietary supplements (eg, St. John's Wort, tryptophan),=
drugs that impair metabolism of serotonin (including monoamine oxidase inh=
ibitors [MAOIs], which are contraindicated with FINTEPLA), dextromethorphan=
, lithium, tramadol, and antipsychotics with serotonergic agonist activity.=
Patients should be monitored for the emergence of signs and symptoms of se=
rotonin syndrome, which include mental status changes (eg, agitation, hallu=
cinations, coma), autonomic instability (eg, tachycardia, labile blood pres=
sure, hyperthermia), neuromuscular signs (eg, hyperreflexia, incoordination=
), and/or gastrointestinal symptoms (eg, nausea, vomiting, diarrhea). If se=
rotonin syndrome is suspected, treatment with FINTEPLA should be stopped im=
mediately and symptomatic treatment should be started.
Increase in Blood Pressure: FINTEPLA can cause an increase in blood pressur=
e. Rare cases of significant elevation in blood pressure, including hyperte=
nsive crisis, has been reported in adult patients treated with fenfluramine=
, including patients without a history of hypertension. In clinical trials =
for DS and LGS of up to 3 years in duration, no pediatric or adult patient =
receiving FINTEPLA developed hypertensive crisis. Monitor blood pressure in=
patients treated with FINTEPLA.
Glaucoma: Fenfluramine can cause mydriasis and can precipitate angle closur=
e glaucoma. Consider discontinuing treatment with FINTEPLA in patients with=
acute decreases in visual acuity or ocular pain.
ADVERSE REACTIONS
The most common adverse reactions observed in DS studies (incidence at leas=
t 10% and greater than placebo) were decreased appetite; somnolence, sedati=
on, lethargy; diarrhea; constipation; abnormal echocardiogram; fatigue, mal=
aise, asthenia; ataxia, balance disorder, gait disturbance; blood pressure =
increased; drooling, salivary hypersecretion; pyrexia; upper respiratory tr=
act infection; vomiting; decreased weight; fall; status epilepticus.
The most common adverse reactions observed in the LGS study (incidence at l=
east 10% and greater than placebo) were diarrhea; decreased appetite; fatig=
ue; somnolence; vomiting.
DRUG INTERACTIONS
Strong CYP1A2, CYP2B6, or CYP3A Inducers: Coadministration with strong CYP1=
A2, CYP2B6, or CYP3A inducers will decrease fenfluramine plasma concentrati=
ons. If coadministration of a strong CYP1A2, CYP2B6, or CYP3A inducer with =
FINTEPLA is necessary, monitor the patient for reduced efficacy and conside=
r increasing the dosage of FINTEPLA as needed. If a strong CYP1A2, CYP2B6, =
or CYP3A inducer is discontinued during maintenance treatment with FINTEPLA=
, consider gradual reduction in the FINTEPLA dosage to the dose administere=
d prior to initiating the inducer.
Strong CYP1A2 or CYP2D6 Inhibitors: Coadministration with strong CYP1A2 or =
CYP2D6 inhibitors will increase fenfluramine plasma concentrations. If FINT=
EPLA is coadministered with strong CYP1A2 or CYP2D6 inhibitors, the maximum=
daily dosage of FINTEPLA is 20 mg. If a strong CYP1A2 or CYP2D6 inhibitor =
is discontinued during maintenance treatment with FINTEPLA, consider gradua=
l increase in the FINTEPLA dosage to the dose recommended without CYP1A2 or=
CYP2D6 inhibitors. If FINTEPLA is coadministered with stiripentol and a st=
rong CYP1A2 or CYP2D6 inhibitor, the maximum daily dosage of FINTEPLA is 17=
mg.
USE IN SPECIFIC POPULATIONS
Administration to patients with hepatic impairment is not recommended.
To report SUSPECTED ADVERSE REACTIONS, contact Zogenix Inc. at 1-866-964-36=
49 (1-866-Zogenix) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch (http:/=
/www.fda.gov/medwatch) .
Please see full Prescribing Information (https://www.zogenix.com/pi/Fintepl=
a-prescribing-information.pdf) , including Boxed Warning, for additional im=
portant information on FINTEPLA.
Important Safety Information about FINTEPLA^=C2=AE=E2=96=BC=C2=A0in the EU =
and EEA^12 =C2=A0
Contraindications
Hypersensitivity to the active substance or any of the excipients of Fintep=
la^=C2=AE. Aortic or mitral valvular heart disease. Pulmonary arterial hype=
rtension. Within 14 days of the administration of monoamine oxidase inhibit=
ors due to an increased risk of serotonin syndrome
Summary of the safety profile=C2=A0
The most commonly reported adverse reactions are decreased appetite (44.2%)=
, diarrhoea (30.8%), pyrexia (25.6%), fatigue (25.6%), upper respiratory tr=
act infection (20.5%), lethargy (17.5%), somnolence (15.4%), and bronchitis=
(11.6%)
Special warnings and precautions for use
Aortic or mitral valvular heart disease and pulmonary arterial hypertension
Because of reported cases of valvular heart disease that may have been caus=
ed by fenfluramine at higher doses used to treat adult obesity, cardiac mon=
itoring must be performed using echocardiography. In the controlled clinica=
l studies of fenfluramine for the treatment of Dravet syndrome, no valvular=
heart disease was observed.
Prior to starting treatment, patients must undergo an echocardiogram to est=
ablish a baseline prior to initiating treatment and exclude any pre-existin=
g valvular heart disease or pulmonary hypertension.
Echocardiogram monitoring should be conducted every 6 months for the first =
2 years and annually thereafter. If an echocardiogram indicates pathologica=
l valvular changes, a follow-up echocardiogram should be considered at an e=
arlier timeframe to evaluate whether the abnormality is persistent. If path=
ological abnormalities on the echocardiogram are observed, it is recommende=
d to evaluate the benefit versus risk of continuing fenfluramine treatment =
with the prescriber, caregiver, and cardiologist.
If treatment is stopped because of aortic or mitral valvular heart disease,=
appropriate monitoring and follow-up should be provided in accordance with=
local guidelines for the treatment of aortic or mitral valvular heart dise=
ase.
With past use in higher doses to treat adult obesity, fenfluramine was repo=
rted to be associated with pulmonary arterial hypertension. Pulmonary arter=
ial hypertension was not observed in the clinical programme, but because of=
the low incidence of this disease, the clinical trial experience with fenf=
luramine is inadequate to determine if fenfluramine increases the risk for =
pulmonary arterial hypertension in patients with Dravet syndrome. If echoca=
rdiogram findings are suggestive of pulmonary arterial hypertension, a repe=
at echocardiogram should be performed as soon as possible and within 3 mont=
hs to confirm these findings. If the echocardiogram finding is confirmed su=
ggestive of an increased probability of pulmonary arterial hypertension def=
ined as =E2=80=9Cintermediate probability=E2=80=9D by the 2015 European Soc=
iety of Cardiology (ESC) and the European Respiratory Society (ERS) Guideli=
nes, it should lead to a benefit-risk evaluation of continuation of Fintepl=
a by the prescriber, carer, and cardiologist. If the echocardiogram finding=
, after confirmation, suggests of a high probability of pulmonary arterial =
hypertension, as defined by the 2015 ESC and ERS Guidelines, it is recommen=
ded fenfluramine treatment should be stopped.
Decreased appetite and weight loss
Fenfluramine can cause decreased appetite and weight loss (see section 4.8)=
. An additive effect on decreased appetite can occur when fenfluramine is c=
ombined with other anti-epileptic medicines, for example stiripentol. The d=
ecrease in weight appears to be dose related. Most subjects resumed weight =
gain over time while continuing treatment. The patient's weight should be m=
onitored. A benefit risk evaluation should be undertaken prior to commencin=
g treatment with fenfluramine in patients with a history of anorexia nervos=
a or bulimia nervosa.
Fintepla controlled access programme
A controlled access programme has been created to 1) prevent off-label use =
in weight management in obese patients and 2) confirm that prescribing phys=
icians have been informed of the need for periodic cardiac monitoring in pa=
tients taking Fintepla.
Somnolence
Fenfluramine can cause somnolence.
Other central nervous system depressants, including alcohol, could potentia=
te the somnolence effect of fenfluramine .
Suicidal behaviour and ideation
Suicidal behaviour and ideation have been reported in patients treated with=
anti-epileptic medicines in several indications. A meta-analysis of random=
ised placebo-controlled trials with anti-epileptic medicines that did not i=
nclude fenfluramine has shown a small increased risk of suicidal behaviour =
and ideation. The mechanism of this risk is not known, and the available da=
ta do not exclude the possibility of an increased risk for fenfluramine. Pa=
tients and caregivers of patients should be advised to seek medical advice =
should any signs of suicidal behaviour and ideation emerge.
Serotonin syndrome
As with other serotonergic agents, serotonin syndrome, a potentially life-t=
hreatening condition, may occur with fenfluramine treatment, particularly w=
ith concomitant use of other serotonergic agents (including SSRIs, SNRIs, t=
ricyclic antidepressants, or triptans); with agents that impair metabolism =
of serotonin such as MAOIs; or with antipsychotics that may affect the sero=
tonergic neurotransmitter systems.
Serotonin syndrome symptoms may include mental status changes (eg, agitatio=
n, hallucinations, coma), autonomic instability (eg, tachycardia, labile bl=
ood pressure, hyperthermia), neuromuscular aberrations (eg, hyperreflexia, =
incoordination), and/or gastrointestinal symptoms (eg, nausea, vomiting, di=
arrhoea).
If concomitant treatment with fenfluramine and other serotonergic agents th=
at may affect the serotonergic systems is clinically warranted, careful obs=
ervation of the patient is advised, particularly during treatment initiatio=
n and dose increases.
Increased seizure frequency
As with other anti-epileptic medicines, a clinically relevant increase in s=
eizure frequency may occur during treatment with fenfluramine, which may re=
quire adjustment in the dose of fenfluramine and/or concomitant anti-epilep=
tic medicines, or discontinuation of fenfluramine, should the benefit-risk =
be negative.
Cyproheptadine
Cyproheptadine is a potent serotonin receptor antagonist and may therefore =
decrease the efficacy of fenfluramine. If cyproheptadine is added to treatm=
ent with fenfluramine, patients should be monitored for worsening of seizur=
es. If fenfluramine treatment is initiated in a patient taking cyproheptadi=
ne, fenfluramine's efficacy may be reduced.
Glaucoma
Fenfluramine can cause mydriasis and can precipitate angle closure glaucoma=
. Discontinue therapy in patients with acute decreases in visual acuity. Co=
nsider discontinuation if there is ocular pain and another cause cannot be =
determined.
Strong CYP1A2 or CYP2B6 inducers
Co-administration with strong CYP1A2 inducers or CYP2B6 inducers may decrea=
se fenfluramine plasma concentrations.
An increase in fenfluramine dosage should be considered when co-administere=
d with a strong CYP1A2 or CYP2B6 inducer; the maximum daily dose should not=
be exceeded.
Excipients
This medicinal product contains sodium ethyl para-hydroxybenzoate (E 215) a=
nd sodium methyl para-hydroxybenzoate (E 219) which may cause allergic reac=
tions (possibly delayed).
It also contains sulfur dioxide (E 220) which may rarely cause severe hyper=
sensitivity reactions and bronchospasm.
Patients with rare glucose-galactose malabsorption should not take this med=
icinal product.
This medicinal product contains less than 1 mmol sodium (23 mg) per the max=
imum daily dose of 12 mL, that is to say essentially 'sodium-free'.
This medicinal product contains glucose which may be harmful to the teeth.
Refer to the European Summary of Product Characteristics for other adverse =
reactions and full prescribing information. Date of revision: 04 Nov 2021.=
=C2=A0
https://www.ema.europa.eu/en/documents/product-information/fintepla-epar-pr=
oduct-information_en.pdf=C2=A0
=E2=96=BC=C2=A0This medicinal product is subject to additional monitoring. =
This will allow quick identification of new safety information. Healthcare =
professionals are asked to report any suspected adverse reactions.=C2=A0
For further information, contact UCB:=C2=A0
Investor Relations
Antje Witte
T +32.2.559.9414
antje.witte@ucb.com
Corporate Communications
Nick Francis
T +44 7769 307745
Nick.francis@ucb.com
Laurent Schots, Media Relations
T+32.2.559.9264
Laurent.schots@ucb.com
Erica Puntel, U.S. Media Relations
T +404 938 5359
Erica.puntel@ucb.com
=C2=A0=C2=A0 =C2=A0
About UCB
UCB, Brussels, Belgium (www.ucb.com) is a global biopharmaceutical company =
focused on the discovery and development of innovative medicines and soluti=
ons to transform the lives of people living with severe diseases of the imm=
une system or of the central nervous system. With approximately 8,600 peopl=
e in approximately 40 countries, the company generated revenue of =E2=82=AC=
5.8 billion in 2021. UCB is listed on Euronext Brussels (symbol: UCB). Foll=
ow us on Twitter: @UCB_news.
Forward looking statements=C2=A0
This press release contains forward-looking statements including, without l=
imitation, statements containing the words =E2=80=9Cbelieves=E2=80=9D, =E2=
=80=9Canticipates=E2=80=9D, =E2=80=9Cexpects=E2=80=9D, =E2=80=9Cintends=E2=
=80=9D, =E2=80=9Cplans=E2=80=9D, =E2=80=9Cseeks=E2=80=9D, =E2=80=9Cestimate=
s=E2=80=9D, =E2=80=9Cmay=E2=80=9D, =E2=80=9Cwill=E2=80=9D, =E2=80=9Ccontinu=
e=E2=80=9D and similar expressions. These forward-looking statements are ba=
sed on current plans, estimates and beliefs of management. All statements, =
other than statements of historical facts, are statements that could be dee=
med forward-looking statements, including but not limited to, the ability o=
f UCB to successfully integrate the operations of Zogenix as planned or at =
all, estimates of revenues, operating margins, capital expenditures, cash, =
other financial information, expected legal, arbitration, political, regula=
tory or clinical results or practices and other such estimates and results.=
By their nature, such forward-looking statements are not guarantees of fut=
ure performance and are subject to known and unknown risks, uncertainties a=
nd assumptions which might cause the actual results, financial condition, p=
erformance or achievements of UCB, or industry results, to differ materiall=
y from those that may be expressed or implied by such forward-looking state=
ments contained in this press release. Important factors that could result =
in such differences include: the global spread and impact of COVID-19, chan=
ges in general economic, business and competitive conditions, the inability=
to obtain necessary regulatory approvals or to obtain them on acceptable t=
erms or within expected timing, costs associated with research and developm=
ent, changes in the prospects for products in the pipeline or under develop=
ment by UCB, effects of future judicial decisions or governmental investiga=
tions, safety, quality, data integrity or manufacturing issues; potential o=
r actual data security and data privacy breaches, or disruptions of our inf=
ormation technology systems, product liability claims, challenges to patent=
protection for products or product candidates, competition from other prod=
ucts including biosimilars, changes in laws or regulations, exchange rate f=
luctuations, changes or uncertainties in tax laws or the administration of =
such laws, and hiring and retention of its employees. There is no guarantee=
that new product candidates will be discovered or identified in the pipeli=
ne, or that new indications for existing products will be developed and app=
roved. Movement from concept to commercial product is uncertain; preclinica=
l results do not guarantee safety and efficacy of product candidates in hum=
ans. So far, the complexity of the human body cannot be reproduced in compu=
ter models, cell culture systems or animal models. The length of the timing=
to complete clinical trials and to get regulatory approval for product mar=
keting has varied in the past and UCB expects similar unpredictability goin=
g forward. Products or potential products which are the subject of partners=
hips, joint ventures or licensing collaborations may be subject to disputes=
between the partners or may prove to be not as safe, effective or commerci=
ally successful as UCB may have believed at the start of such partnership. =
UCB=E2=80=99 efforts to acquire other products or companies and to integrat=
e the operations of such acquired companies may not be as successful as UCB=
may have believed at the moment of acquisition. Also, UCB or others could =
discover safety, side effects or manufacturing problems with its products a=
nd/or devices after they are marketed. The discovery of significant problem=
s with a product similar to one of UCB=E2=80=99s products that implicate an=
entire class of products may have a material adverse effect on sales of th=
e entire class of affected products. Moreover, sales may be impacted by int=
ernational and domestic trends toward managed care and health care cost con=
tainment, including pricing pressure, political and public scrutiny, custom=
er and prescriber patterns or practices, and the reimbursement policies imp=
osed by third-party payers as well as legislation affecting biopharmaceutic=
al pricing and reimbursement activities and outcomes. Finally, a breakdown,=
cyberattack or information security breach could compromise the confidenti=
ality, integrity and availability of UCB=E2=80=99s data and systems.
Given these uncertainties, you should not place undue reliance on any of su=
ch forward-looking statements. There can be no guarantee that the investiga=
tional or approved products described in this press release will be submitt=
ed or approved for sale or for any additional indications or labelling in a=
ny market, or at any particular time, nor can there be any guarantee that s=
uch products will be or will continue to be commercially successful in the =
future.
UCB is providing this information, including forward-looking statements, on=
ly as of the date of this press release and expressly disclaims any duty to=
update any information contained in this press release, either to confirm =
the actual results or to report or reflect any change in its forward-lookin=
g statements with regard thereto or any change in events, conditions or cir=
cumstances on which any such statement is based, unless such statement is r=
equired pursuant to applicable laws and regulations.
Additionally, information contained in this document shall not constitute a=
n offer to sell or the solicitation of an offer to buy any securities, nor =
shall there be any offer, solicitation or sale of securities in any jurisdi=
ction in which such offer, solicitation or sale would be unlawful prior to =
the registration or qualification under the securities laws of such jurisdi=
ction.
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mation. March 2022. Available at : https://zogenix.com/pi/Fintepla-prescrib=
ing-information.pdf. Last accessed: April 2022=C2=A0
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pediatrics. 2017;48(3):143-151.
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1.pdf. Accessed April 2022.
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A^=C2=AE (Fenfluramine) in Japan for the Treatment of Epileptic Seizures As=
sociated with Dravet Syndrome. 21 December 2021. Available at: https://www.=
globenewswire.com/news-release/2021/12/21/2356048/0/en/Zogenix-Submits-New-=
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GenericFile
220429 JAMA Neurology FINTEPLA LGS press release ENG (https://mb.cision.com=
/Public/18595/3558558/a88674e492a09b22.pdf)
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