No parent, sibling, or close relative is prepared for the shock of a child eventually being diagnosed with a rare disease -- a diagnostic odyssey that takes seven years, on average. Families manage as best they can under the most trying conditions. Out of necessity, they quickly become experts in the methods and means to optimally care for, and comfort, their child.
Many rare epilepsies affect only a few hundred or, at most, a few thousand people. Research about these conditions is limited. But resources are available and growing. Among these resources are effective, well led rare disease organizations. Two of our most vital partners are the Dravet Syndrome Foundation (DSF) and Lennox-Gastaut Syndrome (LGS) Foundation.
Guided by Mary Anne Meskis and Dr. Tracy Dixon-Salazar, respectively, these groups help the families of two different rare, difficult to treat epilepsies. The incidence rate for Dravet syndrome is about one per 16,000 births. LGS impacts approximately 2.6 out of every 10,000 United States children with total cases ranging from 39,045 to 47,800 people.1
The frequency of seizures, sometimes several hundred per day, can severely diminish intellectual development during childhood. While it doesn’t work for everyone – and results frequently differ per individual – clinical studies find that FINTEPLA® (fenfluramine) oral solution C-IV, can significantly reduce seizure frequency.
Please see below for Important Safety Information including Boxed Warning and Prescribing Information and Medication Guide for FINTEPLA.
Mary Anne and Tracy – both parents of children affected by one of these disorders – say they found the willingness to listen and tailor the clinical trial procedures to the needs of both patients and caregivers gratifying and encouraging.
“We were pleasantly surprised because you really came in and said to us, 'You're the experts. We want to learn from you so that we can make sure that we're designing the studies to help your kids. We want to know and learn as many ways as possible to engage your community’,” said Mary Anne. “And then [you] did just that. It was very much appreciated early on.”
The rare epilepsy community provided invaluable advice and feedback during the testing of FINTEPLA. During the clinical trials for FINTEPLA, our clinical study used e-diaries to capture seizures experienced by patients. We believed that real-time, digitally reported data by caregivers would be more accurate and precise.
The U.S. Food and Drug Administration (FDA) eventually agreed, clearing the way for e-diaries to be used in other drug trials as well.
Tracy, a neuroscientist whose daughter was diagnosed Lennox-Gastaut Syndrome at two years old, was similarly impressed. She had heard that FINTEPLA was showing promise in the Dravet and was hopeful for similar positive results when drug trials began with LGS patients.
“We were eager for help,” Tracy said. “The [company’s clinical trials] team reached out, wanting to develop their clinical drug trial program around us and our community. It was very exciting, and exactly what the patient family groups want. They really distinguished themselves from some of the other pharmaceutical companies we were beginning to work with.”
Despite challenges and several setbacks validating the pioneering e-diaries reporting process during the complex regulatory approval process, the FDA approved FINTEPLA for the treatment of seizures associated with Dravet syndrome in patients two years of age and older in 2020 and for the treatment of seizures associated with Lennox-Gastaut Syndrome in patients two years of age and older in 2022 through an expedited approval.
“It was really beneficial that we as a community felt we were part of this team — a team working together, looking for better answers to help our children and kids everywhere suffering from Dravet syndrome,” Mary Anne said, reflecting on the FDA approval. “We can feel a little more confident about seizure freedom.”
“It opens up the world and allows the families and affected children to have the types of meaningful childhood experiences most parents take for granted,” Mary Anne continued. “Better seizure control gives families the peace of mind to plan ahead and feel comfortable doing everyday things, such as going on a vacation, without [constantly] worrying about what will happen if they end up in a hospital in a different city where no one knows or understands their loved one's medical needs.”
Tracy said UCB’s teams continue to engage her patient community in a positive way. “I’ve seen them consistently put the patient voice and patient interest first,” she says. “It gives us a feeling we have somebody on the inside who’s advocating for us all the way up the chain of command.”
Brad Chapman, Head of U.S. Epilepsy and Rare Syndromes for UCB, sums up the approach this way: “Partnership and collaboration with the Dravet and LGS Foundations are essential to achieve better outcomes and ensure we are truly listening to and understanding the experiences these families and their loved ones are going through. We know the health care system isn’t built to address the unique needs of rare epilepsy syndromes. To be successful in elevating care we need to partner, listen, and co-create solutions that matter.”
About FINTEPLA® (fenfluramine) C-IV
FINTEPLA® (fenfluramine) oral solution is a prescription medication approved by the FDA and authorized by the EU Commission, and under regulatory review with the PMDA (Japan), for the treatment of seizures associated with Dravet syndrome in patients two years of age and older.3,4 FINTEPLA is also approved in the U.S. for the treatment of seizures associated with Lennox-Gastaut syndrome.2 Application has also been submitted and is currently under assessment by the European Medicines Agency (EMA) for the treatment of seizures associated with LGS.5
In the United States, FINTEPLA is available only through a restricted distribution program called the FINTEPLA REMS program. FINTEPLA is available in Europe under a controlled access program requested by the EMA to prevent off-label use for weight management and to confirm that prescribing physicians have been informed of the need for periodic cardiac monitoring in patients taking FINTEPLA. Further information is available at www.FinteplaREMS.com or by telephone at +1 877 964 3649.
Please see full Prescribing Information, including Boxed Warning, for additional important 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
- There is an association between serotonergic drugs with 5-HT2B receptor agonist activity, including fenfluramine (the active ingredient in FINTEPLA), and 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.
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):
Because of the association between serotonergic drugs with 5 HT2B receptor agonist activity, including fenfluramine (the active ingredient in FINTEPLA), and valvular heart disease (VHD) and pulmonary arterial hypertension (PAH), cardiac monitoring via echocardiogram is required prior to starting treatment, during treatment, and after treatment with FINTEPLA concludes. Cardiac monitoring via echocardiogram can aid in early detection of these conditions. In clinical trials for DS and LGS of up to 3 years in duration, no patient receiving FINTEPLA developed VHD or PAH.
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 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 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 (eg, valve thickening or restrictive valve motion); PAH indicated by elevated right heart/pulmonary artery pressure (PASP >35mmHg).
FINTEPLA REMS Program (see Boxed Warning): FINTEPLA is available only through a restricted distribution program called the FINTEPLA Risk Evaluation and Mitigation Strategy (REMS) Program. Prescribers must be certified by enrolling in the FINTEPLA REMS. Prescribers must counsel patients receiving FINTEPLA about the risk of valvular heart disease and pulmonary arterial hypertension, how to recognize signs and symptoms of valvular heart disease and pulmonary arterial hypertension, the need for baseline (pretreatment) and periodic cardiac monitoring via echocardiogram during FINTEPLA treatment, and 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 distributors 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 appetite and weight. Decreases in weight appear to be dose related. Approximately half of the patients with LGS and most patients with DS resumed the expected 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 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.
Anyone considering prescribing FINTEPLA or any other AED must balance the risk of suicidal thoughts or behaviors with the risks of untreated illness. Epilepsy and many other illnesses for which AEDs are prescribed are themselves associated with morbidity and mortality and an increased risk of suicidal thoughts and behaviors. Should suicidal thoughts and behaviors emerge during treatment, consider whether the emergence of these symptoms in any given patient may be related to the illness being treated.
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 (eg, 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 (eg, agitation, hallucinations, coma), autonomic instability (eg, tachycardia, labile blood pressure, hyperthermia), neuromuscular signs (eg, hyperreflexia, incoordination), and/or gastrointestinal symptoms (eg, nausea, vomiting, diarrhea). 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, 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 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.
DRUG INTERACTIONS Strong CYP1A2, CYP2B6, or CYP3A Inducers: Coadministration with strong CYP1A2, CYP2B6, or CYP3A inducers will decrease fenfluramine plasma concentrations. If coadministration of a strong CYP1A2, CYP2B6, or CYP3A inducer with FINTEPLA is necessary, monitor the patient for reduced efficacy and consider 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 administered prior to initiating the inducer.
Strong CYP1A2 or CYP2D6 Inhibitors: Coadministration with strong CYP1A2 or CYP2D6 inhibitors will increase fenfluramine plasma concentrations. If FINTEPLA 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 gradual increase in the FINTEPLA dosage to the dose recommended without CYP1A2 or CYP2D6 inhibitors. If FINTEPLA is coadministered with stiripentol and a strong 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 1-866-964-3649 (1-866-Zogenix) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
Please see full Prescribing Information, including Boxed Warning, for additional important information on FINTEPLA.
- How Many People Have LGS? -LGS Foundation
- FINTEPLA® (fenfluramine) oral solution CIV. U.S. Prescribing Information. March 2022.
- FINTEPLA Summary of Product Characteristics. January 2022.
- Zogenix Press Release. Zogenix Submits New Drug Application for FINTEPLA® (Fenfluramine) in Japan for the Treatment of Epileptic Seizures.
- Zogenix Press Release. Zogenix Submits Type II Variation Application to the European Medicines Agency (EMA) to Expand the Use of FINTEPLA® (fenfluramine) for the Treatment of Seizures Associated with Lennox-Gastaut Syndrome. 20 December 2021.
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