5 July 2018

Now PBS listed: BRIVIACT® (brivaracetam) for the add-on treatment of partial-onset (focal) seizures [1]

Drugs PBS SPONSORED

An antiepileptic add-on treatment that has been shown to be effective without the need to titrate for tolerability, is now available on the Pharmaceutical Benefits Scheme (PBS).2

 BRIVIACT® (brivaracetam) is an add-on therapy for the treatment of partial-onset seizures with or without secondary generalisation in patients from 16 years of age with epilepsy.1 The therapy is available in three formulations – oral tablets, oral solution1 (currently unavailable for supply) or solution for injection by a healthcare professional, when oral administration is temporarily not possible (solution for injection is not PBS reimbursed).3

 The efficacy of BRIVIACT® was established in three fixed-dose, randomised, double-blind, placebo-controlled, multi-centre studies, across 1,558 patients.1,4-6 Despite ongoing treatment with one-to-two concomitant antiepileptic drugs (AEDs), the adjunct use of BRIVIACT® 100 mg/day was associated with a clinically significant 24.4 per cent reduction in 28-day adjusted seizure frequency over placebo (p<0.001).7 Furthermore, over a 12-week period, partial-onset seizures were more than halved from baseline in 39.5 per cent of patients treated with BRIVIACT® 100 mg/day.1

According to Professor Patrick Kwan, Head of Epilepsy at The Royal Melbourne Hospital and Alfred Hospital, Melbourne, as many as 250,000 Australians are currently living with epilepsy and 800,000 will develop epilepsy in their lifetime.8

“People living with epilepsy can face daily challenges due to uncertainty about when they might experience their next seizure. An add-on therapy that can significantly reduce seizure frequency, or even facilitate seizure freedom,4-6 is a welcome addition to the array of available AEDs.

“Not everyone responds in the same way to AEDs or their various interactions with other drugs, so therapies such as brivaracetam, that can be taken together with most other medications, antiepileptic or otherwise,1 have an advantage in implementing personalised seizure management,” said Prof Kwan.

BRIVIACT® displays a high and selective affinity for synaptic vesicle protein 2A (SV2A) in the brain, which is thought to be the primary mechanism for its anticonvulsant effect. However, the precise mechanism of BRIVIACT®’s contribution to anticonvulsant activity is unknown.1,9

BRIVIACT® was found to be effective in patients who had previously failed levetiracetam (another SV2A ligand).4 However, there was no observed benefit when the two AEDs were used concomitantly.1,5,6

Prof Kwan emphasises the need for more effective antiepileptic treatment.4

“Despite the availability of third-generation AEDs with various mechanisms of action, the proportion of people living with epilepsy, particularly focal epilepsy, that remains uncontrolled by AEDs, has not significantly changed since the 1990s.10-12

“Though the precise mechanism of brivaracetam’s anticonvulsant activity is unknown, the SV2A ligand is known to be implicated in effective seizure management.1,9 It is critical to further our understanding of the causes of epilepsy and the anticonvulsant mechanisms in existing AEDs, in order to harness these processes to develop more effective treatments,” Prof Kwan said.

A therapeutic dose of BRIVIACT® 50 mg twice daily (100 mg/day) can be administered from day one without the need for up-titration.1 Across the three pivotal clinical trials, use of BRIVIACT® was generally well tolerated, even at higher doses of 200 mg/day,4 and showed low discontinuation rates due to adverse events.4-6,7

The most commonly reported adverse events (>5%) were somnolence (or drowsiness) (15.2%), dizziness (11.2%), headache (9.6%) and fatigue (8.7%) and were usually mild to moderate in intensity.7 The dose should be monitored in patients with any form of renal impairment and a maximum daily dose of 150 mg is recommended in any form of hepatic impairment.1

According to Graeme Shears, CEO Epilepsy Foundation, less disruptive treatments are crucial to improving patient outcomes.

“Living with epilepsy can significantly impact patients’ lives, if not effectively managed.13,14 The continued development of improved antiepileptic treatments, minimising disruption to patients’ activities of daily living, is welcomed by patients and carers alike,” Graeme said.

About BRIVIACT®

 BRIVIACT® displays a high and selective affinity for SV2A1,8 and does not display activity at high-voltage activated Ca2+ channels or ? -amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors.8 There is no evidence that BRIVIACT® prolongs the QT interval. A statistically significant correlation has been demonstrated between BRIVIACT® plasma concentration and seizure frequency reduction from baseline in adjunctive treatment of partial onset seizures.1,15

BRIVIACT® is rapidly absorbed following oral administration, and the extent of absorption is unchanged by food. Due to its high membrane permeability, BRIVIACT® rapidly penetrates into the brain. BRIVIACT® is eliminated primarily by metabolism and by excretion in the urine.1 The terminal plasma half-life is approximately 9 hours. BRIVIACT® is not expected to cause clinically significant inhibition or induction of the clearance of other drugs metabolised by CYP450 isoforms.1 The pharmacokinetics of BRIVIACT® are not significantly affected by gender or race, and no dose adjustment is required in patients aged over 65. The safety and effectiveness of BRIVIACT® has not been established in neonates or children aged under 16.1

About epilepsy

 Epilepsy is a diverse group of complex brain disorders resulting in recurrent seizures16 and is the world’s most common serious brain disorder.7 Seizures occur when there is sudden, excessive electrical activity in a group of brain cells, and symptoms range from brief attention lapses, muscle jerks and repetitive movements, to severe and prolonged convulsions and loss of consciousness. A person with epilepsy has two or more unprovoked seizures.17 Epilepsy is a neurological disorder, not a mental illness, and while the cause of epilepsy in many people is unknown, more than 70 per cent of people are able to become seizure free with AEDs.10

Partial-onset seizures, also known as focal-onset seizures, affect around 60 per cent of people of with epilepsy.18 Seizures of this kind start in one area of the brain, but can spread to other regions, and are classified by changes in awareness and movement, including muscle jerks, hallucinations and altered emotions, consciousness or sensations.17,18 When awareness is retained, seizures are classified as focal aware seizures. When awareness is altered, seizures are known as focal impaired awareness seizures. Should the seizure activity spread to both hemispheres of the brain, this reflects the change from a focal seizure to a bilateral tonic clonic seizure, characterised by muscles stiffening and jerking.18

About UCB

 UCB aspires to be the patient-centric global biopharmaceutical leader, transforming the lives of people with severe diseases. At UCB, the sense of purpose is to help people suffering from severe central nervous system disorders lead normal, everyday lives. UCB’s ambition is to offer them innovative new medicines and ground-breaking solutions that go beyond the drug. They are committed to enabling cutting-edge scientific research that is driven by patients’ needs.

For more information, visit https://www.ucbaustralia.com.au or call (03) 9828 1800.

PBS Information: Tablets and Oral Solution: Authority Required (STREAMLINED). Refer to PBS schedule for full authority information. Injection: This product is not listed on the PBS.

 Please review Product Information before prescribing.

Product Information can be accessed at

http://www.ucbpharma.com.au/Briviact-oral

http://www.ucbpharma.com.au/Briviact-IV

 MINIMUM PRODUCT INFORMATION.

 Briviact® (brivaracetam) 10 mg, 25 mg, 50 mg, 75 mg, 100 mg tablets, 10 mg/mL oral solution, 50 mg/5 mL IV solution. Minimum Product Information. Indications: Briviact tablets and oral solution are indicated as add-on therapy in the treatment of partial-onset seizures with or without secondary generalisation in patients from 16 years of age with epilepsy. Brivaracetam solution for injection is an alternative for patients when oral administration is temporarily not feasible. Contraindications: Hypersensitivity to the active substance or to any of the excipients. Precautions: Do not withdraw abruptly. Pregnancy. Children. Elderly. Hepatic Impairment. Driving or operating machinery. AEDs, including brivaracetam, increase the risk of suicidal thoughts or behaviour. Patients treated with any AED for any indication should be monitored for the emergence or worsening of depression, suicidal thoughts or behaviour, and/or any unusual changes in mood or behaviour. Interactions: Rifampicin, carbamazepine, phenobarbital and phenytoin decrease brivaracetam plasma concentrations. Adverse effects: Vertigo, nausea, vomiting, constipation, fatigue, irritability, upper respiratory tract infection, influenza, somnolence, dizziness, insomnia, anxiety, depression, cough. Others see PI. Dosage and method of use: Initial dose titration to an effective dose is not required for tolerability. Daily dose is administered in two equally divided doses, once in the morning and once in the evening. The recommended starting dose as per clinical trials is 100 mg/day but may be initiated at a dose of 50 mg per day. Based on individual patient response, the dose may be adjusted between 50 mg/day and 200 mg/day in steps of 50 mg per day every 2 weeks. Date first included on ARTG: 4th August 2016. Date of most recent amendment: 25th May 2017.

Briviact® is a registered trademark of UCB Biopharma SPRL.

Prof Kwan has served on advisory boards and been involved in clinical trials sponsored by UCB. In relation to this UCB media announcement, no compensation was provided to Prof Kwan or Graeme Shears, and their opinions expressed are their own.

References

 BRIVIACT® (2017) Australian Prescribing Information BRIVIACT® (brivaracetam) – Tablets and oral solution. Available at: http://www.ucbpharma.com.au/Briviact-oral.

  1. Australian Government. The Pharmaceutical Benefits Scheme. Department of Health. Available at: http://www.pbs.gov.au/pbs/search?term=brivaracetam&analyse=false&search-type=medicines.
  2. BRIVIACT® (2017) Australian Prescribing Information BRIVIACT® (brivaracetam) – Solution for injection. Available at: http://www.ucbpharma.com.au/Briviact-IV.
  3. Klein P, Schiemann J, Sperling MR, Whitesides J, Liang W, Stalvey T, Brandt C, & Kwan P. (2015) A randomized, double-blind, placebo-controlled, multicenter, parallel-group study to evaluate the efficacy and safety of adjunctive brivaracetam in adult patients with uncontrolled partial-onset seizures. Epilepsia. 56(12):1890–1898.
  4. Ryvlin P, Werhahn KJ, Blaszczyk B, Johnson ME, & Lu S. (2014) Adjunctive brivaracetam in adults with uncontrolled focal epilepsy: Results from a double-blind, randomized, placebo-controlled trial. Epilepsia. 55(1):47–56.
  5. Biton V, Berkovic SF, Abou-Khalil B, Sperling MR, Johnson ME, & Lu S. (2014) Brivaracetam as adjunctive treatment for uncontrolled partial epilepsy in adults: A phase III randomized, double-blind, placebo-controlled trial. Epilepsia. 55(1):57–66.
  6. Ben-Menachem E, Mameniškien? R, Quarato P, Klein P, Gamage J, Schiemann, J Johnson M, Whitesides J, McDonough B, Eckhardt K (2016) Efficacy and safety of brivaracetam for partial-onset seizures in 3 pooled clinical studies. Neurology, 873:314-323.
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  8. Klitgaard H, Matagne A, Nicolas J,  Gillard M,  Lamberty Y,  De Ryck M,  Kaminski R, Leclercq K,  Niespodziany I,  Wolff C,  Wood M,  Hannestad J,  Kervyn S, & Kenda B. (2016) Brivaracetam: Rationale for discovery and preclinical profile of a selective SV2A ligand for epilepsy treatment. Epilepsia, 57:538-548.
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  16. World Health Organization (WHO) (2012) Epilepsy Fact sheet no. 999. Available at http://www.who.int/mediacentre/factsheets/fs999/en/index.html. Last accessed 14 May 2018.
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