Primary and secondary endpoints
Patients taking FINTEPLA 0.7 mg/kg/day1
FINTEPLA 0.7 mg/kg/day (n=83) reduced monthly seizures resulting in drops or falls* by 23.7% from baseline over 14 weeks1
Compared with an 8.7% reduction for patients receiving placebo (n=85; P=0.0037)
*Seizures resulting in drops or falls included generalized tonic-clonic, tonic, atonic, and tonic-atonic seizures.
The total number of patients on whom this efficacy analysis was based is less than the total number randomized in the double-blind, placebo-controlled study because patients with missing data were excluded from the efficacy analysis.1
A 0.2 mg/kg/day dose of FINTEPLA did not reach statistical significance compared with placebo.1
Study design:
- • FINTEPLA was evaluated for use in LGS in a Phase 3, multicenter, randomized, double-blind, parallel-group,
placebo-controlled trial (N=263) in patients aged 2 to 35 years over 14 weeks1,2 - • Patients at baseline had previously tried up to 4 ASMs and had at least 8 drop/fall seizures per month, a median of 10-18
GTC seizures per month, and a mean of 194 seizures per month; ~40% of patients had interventional procedures1-3
Aaron, a patient taking FINTEPLA
“I didn’t expect FINTEPLA to be the silver bullet for Aaron.
I just wanted to see if it would reduce his seizures. And it did.”
― Jennifer, mother of Aaron
Jennifer was compensated for her testimonial.
Broad-spectrum efficacy, including reductions
in life-threatening seizures2
Patients receiving FINTEPLA 0.7 mg/kg/day experienced
the following median percentage SEIZURE REDUCTIONS2
LIFE-THREATENING Seizures with serious risk of resulting in a drop or fall
Offer seizure reduction to your patients experiencing a range of life-threatening seizures.1,4
Discover more about FINTEPLA for your patients with LGS
Open-label extension
Consistent safety and efficacy observed over
15 months in the open-label extension (OLE)5
The results of this open-label, uncontrolled study are exploratory; therefore, no conclusions of efficacy should be made
Frequency of seizures resulting in a drop or fall over time5
MEDIAN CHANGE IN DROP SEIZURE FREQUENCY OF 50.5% AT MONTH 15
94% of patients who completed Study 3 opted to participate in the long-term, flexible-dose, OLE study.5
- • FINTEPLA reduced the frequency of seizures resulting in a drop or fall in patients who weighed ≥37.5 kg and had their dose capped at 26 mg, which resulted in a weight-based dose below 0.7 mg/kg/day6
- • The treatment-emergent adverse event (TEAE) profile in the OLE study was comparable to the 14-week clinical trial. No unexpected or new TEAEs emerged5
- • All patients in the OLE study started at a dose of 0.2 mg/kg/day and subsequently titrated up to their maintenance dose5
- • The discontinuation rate due to TEAEs in the OLE was 4.9% (n=12)5
- •The results of this open-label, uncontrolled study are exploratory; therefore, no conclusions of efficacy should be made
Choose FINTEPLA for reductions that can continue in the long term5
Over the entire OLE, patients continuing with FINTEPLA experienced
the following median percentage seizure reductions5†
†From Month 2 to end of study (entire OLE duration). Median percentage change from pre-randomization baseline.
Seizure-free days
Give your patients a chance at consecutive seizure-free days2
Longest interval between seizures resulting in a drop or fall in the OLE2
50% of patients experienced
≥7
consecutive
seizure-free days
25% of patients experienced
≥17
consecutive
seizure-free days
At baseline, patients were experiencing a median of 75 drop seizures per 28 days.5
Study design
Studied in patients with refractory and
difficult-to-treat seizures1
Study design:
- • FINTEPLA was evaluated for use in LGS in a Phase 3, multicenter, randomized, double-blind, parallel-group, placebo-controlled trial (N=263) in patients aged 2 to 35 years over 14 weeks1,2
AT BASELINE
Treatment history1,2
Up to 4 ASMs
(baseline treatment)
~40% of patients had interventional procedures
including vagal nerve stimulation (VNS) and corpus callosotomy
SEIZURE frequency (per month)1-3
At least
8
drop/fall
seizures
Median of
10-18
GTC
seizures
Mean of
194
seizures
Patients also had an average of 7 prior ASMs at trial initiation, including levetiracetam, clobazam, topiramate, valproate, rufinamide, and cannabidiol.2
Discover behavior, emotion, and cognition results for patients treated with FINTEPLA2,7
Learn about how FINTEPLA profoundly (≥75%) reduced seizures for patients with Dravet syndrome1,2,8
Connect with a FINTEPLA representative
ASM, antiseizure medication; GTC, generalized tonic-clonic.
Important Safety Information
BOXED WARNING: VALVULAR HEART DISEASE and PULMONARY ARTERIAL HYPERTENSION
- FINTEPLA can cause valvular heart disease and pulmonary arterial hypertension.
- Echocardiogram assessments are required before, during, and after treatment with FINTEPLA.
- FINTEPLA is available only through a restricted program called the FINTEPLA REMS.
CONTRAINDICATIONS
FINTEPLA is contraindicated in patients with hypersensitivity to fenfluramine or any of the excipients in FINTEPLA and with concomitant use, or within 14 days of the administration, of monoamine oxidase inhibitors because of an increased risk of serotonin syndrome.
WARNINGS AND PRECAUTIONS
Valvular Heart Disease and Pulmonary Arterial Hypertension (see Boxed Warning): FINTEPLA can cause valvular heart disease (VHD) and pulmonary arterial hypertension (PAH). Although no patients receiving FINTEPLA developed VHD or PAH in clinical trials for DS and LGS of up to 3 years in duration, cases of VHD and PAH have been reported during use of FINTEPLA in the postmarketing setting. Because of this risk, cardiac monitoring is required prior to starting treatment, during treatment, and after treatment with FINTEPLA concludes. Cardiac monitoring via echocardiogram can identify evidence of VHD and PAH prior to a patient becoming symptomatic, aiding in early detection of these conditions.
Monitoring: Prior to starting treatment, patients must undergo an echocardiogram to evaluate for VHD and PAH. Echocardiograms should be repeated every 6 months, and once 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 observed via echocardiogram: valvular abnormality or new abnormality; VHD indicated by mild or greater aortic regurgitation or moderate or greater mitral regurgitation, with additional characteristics of VHD (e.g., valve thickening or restrictive valve motion); PAH indicated by elevated right heart/pulmonary artery pressure (PASP >35 mm Hg).
FINTEPLA REMS (see Boxed Warning): FINTEPLA is available only through a restricted distribution program called the FINTEPLA Risk Evaluation and Mitigation Strategy (REMS). Prescribers must be certified by enrolling in the FINTEPLA REMS. Prescribers must counsel patients receiving FINTEPLA about the risk of VHD and PAH, how to recognize signs and symptoms of VHD and PAH, the need for baseline (pretreatment) and periodic cardiac monitoring via echocardiogram during FINTEPLA treatment, and cardiac monitoring after FINTEPLA treatment.
Decreased Appetite and Decreased Weight: FINTEPLA can cause decreases in appetite and weight. Decreases in weight appear to be dose related. 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 depressants, including alcohol, could potentiate these effects of FINTEPLA. Prescribers should monitor 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 operate machinery.
Suicidal Behavior and Ideation: Antiepileptic drugs (AEDs), including FINTEPLA, increase the risk of suicidal thoughts or behaviors in patients taking these drugs for any indication. Patients treated with an AED for any indication should be monitored for the emergence or worsening of depression, suicidal thoughts or behaviors, or any unusual changes in mood or behavior.
Withdrawal of Antiepileptic Drugs: As with most AEDs, FINTEPLA should generally be withdrawn gradually because of the risk of increased seizure frequency and status epilepticus. If withdrawal is needed because of a serious adverse reaction, rapid discontinuation can be considered.
Serotonin Syndrome: Serotonin syndrome, a potentially life-threatening condition, may occur with FINTEPLA, particularly during concomitant administration of FINTEPLA with other serotonergic drugs, including, but not limited to, selective serotonin-norepinephrine reuptake inhibitors (SNRIs), selective serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants (TCAs), bupropion, triptans, dietary supplements (e.g., St. John’s Wort, tryptophan), drugs that impair metabolism of serotonin (including monoamine oxidase inhibitors [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 serotonin syndrome, which include mental status changes, autonomic instability, neuromuscular signs, and/or gastrointestinal symptoms. If serotonin syndrome is suspected, treatment with FINTEPLA should be stopped immediately and symptomatic treatment should be started.
Increase in Blood Pressure: FINTEPLA can cause an increase in blood pressure. Rare cases of significant elevation in blood pressure, including hypertensive crisis, have 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 closure 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 least 10% and greater than placebo) were decreased appetite; somnolence, sedation, lethargy; diarrhea; constipation; abnormal echocardiogram; fatigue, malaise, asthenia; ataxia, balance disorder, gait disturbance; blood pressure increased; drooling, salivary hypersecretion; pyrexia; upper respiratory tract infection; vomiting; decreased weight; fall; status epilepticus.
The most common adverse reactions observed in the LGS study (incidence at least 10% and greater than placebo) were diarrhea; decreased appetite; fatigue; somnolence; vomiting.
To report SUSPECTED ADVERSE REACTIONS, contact UCB, Inc. at 1-844-599-2273 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
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.
Please see full Prescribing Information, including Boxed Warning, for additional Important Safety Information.
References
1. FINTEPLA (fenfluramine) oral solution: U.S. prescribing information. Smyrna, GA: UCB, Inc. 2. Data on file. UCB, Inc. 3. Knupp KG, Scheffer IE, Ceulemans B, et al. Efficacy and safety of fenfluramine for the treatment of seizures associated with Lennox-Gastaut syndrome: a randomized clinical trial. JAMA Neurol. 2022;79(6):554-564. 4. Chin RFM, Pickrell WO, Guelfucci F, Martin M, Holland R. Prevalence, healthcare resource utilization and mortality of Lennox-Gastaut syndrome: retrospective linkage cohort study. Seizure. 2021;91:159-166. 5. Knupp KG, Scheffer IE, Ceulemans B, et al. Fenfluramine provides clinically meaningful reduction in frequency of drop seizures in patients with Lennox-Gastaut syndrome: interim analysis of an open-label extension study. Epilepsia. 2023;64(1):139-151. 6. Knupp KG, Scheffer IE, Ceulemans B, et al. Impact of fenfluramine in patients with Lennox-Gastaut syndrome: subgroup analysis of dose-capping on drop seizure frequency reduction in the open-label extension data. Presented at: American Epilepsy Society 76th Annual Meeting; December 2-6, 2022; Nashville, TN. 7. Lagae L, Sullivan J, Knupp K, et al. Fenfluramine hydrochloride for the treatment of seizures in Dravet syndrome: a randomised, double-blind, placebo-controlled trial. Lancet. 2019;394(10216):2243-2254. 8. Bishop KI, Isquith PK, Gioia GA, et al. Improved everyday executive functioning following profound reduction in seizure frequency with fenfluramine: analysis from a phase 3 long-term extension study in children/young adults with Dravet syndrome. Epilepsy Behav. 2021;121(Pt A):108024.
