viernes, 15 de abril de 2016

Eisai epilepsy data presented at the American Academy of Neurology (AAN) annual meeting‏

 Data show that seizure control improves regardless of age, sex and ethnicity in drug-resistant patients with primary generalised tonic-clonic (PGTC) seizures treated with once-daily adjunctive Fycompa®(perampanel) at doses up to 8mg per day.]  These data are one of a number of perampanel and Inovelon® (rufinamide) abstracts presented this week at the American Academy of Neurology (AAN) Annual Meeting Vancouver, Canada.

The results show that a change in seizure frequency from baseline is greater with perampanel than with placebo across all groups and similar for placebo between age, sex, and ethnicity. Data are obtained from a double-blind, placebo-controlled Phase III study in 162 patients with idiopathic generalised epilepsy (IGE) (81 each on either perampanel or placebo) who have confirmed PGTC seizures.

“These data confirm that adjunctive perampanel provides effective management of seizures in all groups of IGE patients studied with primary generalised tonic-clonic seizures,” comments Bernhard Steinhoff, Medical Director and Executive Chief Physician, Kork Epilepsy Centre, Germany.

Post-hoc analysis of this Phase III study of adjunctive perampanel for primary tonic-clonic seizures across age, sex and ethnicity shows similar median percent change from baseline in primary generalised tonic-clonic seizure frequency for age (age <18y nbsp="" span="">-88.0%; age ≥18−<65y nbsp="" span="">-74.4%), sex (males, -53.3%; females, -83.0%) and ethnic groups (White, -65.5%; Asian/Pacific, -79.1%).  The 50% responder rate is also similar across age (age <18y 53.8="" age="" span="">-<65y 54.3="" 58.8="" 66.2="" 68.2="" 71.7="" acific="" and="" asian="" ethnic="" females="" groups="" hite="" males="" sex="" span="">

Perampanel has shown efficacy in, and is indicated for the adjunctive treatment of partial-onset seizures with or without secondarily generalised seizures in adult and adolescent patients from 12 years of age with epilepsy; and for the adjunctive treatment of primary generalised tonic-clonic seizures in adult and adolescent patients from 12 years of age with idiopathic generalised epilepsy. 

Data presented from this Phase III study in PGTC seizures explores the relationship between perampanel exposure, primary generalised tonic-clonic seizure outcomes, and treatment-emergent adverse events (TEAEs) in patients with uncontrolled primary generalised      tonic-clonic seizures. Response rate increases, and responder probability is predicted to increase with increased perampanel exposure.  Concomitant use of enzyme-inducing anti-epileptic drugs (EIAED) reduces perampanel exposure, and perampanel exposure is higher in patients with hostility/aggression-related TEAEs than in those without, although the concentrations overlap substantially.3

Abstract P2.045 17 April 08:30-17:30 PDT French J et al
Data from an external review was used for the first time to ensure the appropriate classification of trial participants4 withprimary generalised tonic-clonic seizures in the Phase III perampanel PGTC trial. An independent group review eliminated almost a third (29.9%) of patients, initially considered eligible, from inclusion in perampanel’s pivotal study 332.  Without this review the interpretability of results may otherwise be compromised.4  

With the advent of newer medications for primary generalised tonic-clonic seizures the standard of care (SOC) has changed over time while trial designs remain similar over time, according to a systematic literature review of published data during 1989-2014 of different anti-epileptic drug (AED) trials versus placebo for adjunctive treatment of primary generalised tonic-clonic seizures. The latest trial, the perampanel Phase III study 3325 includes a standard of care that is weighted to the most recently approved drugs for primary generalised tonic-clonic seizures such as topiramate, lamotrigine, levetiracetam, and valproate.  

In patients with partial seizures, results of an extension study shows that treatment with perampanel for three or four years significantly improves seizure control, and is well tolerated as an adjunctive treatment At three years’ exposure to perampanel, median seizure reduction is 61.98% and at four years’ exposure is 70.63%.  The largest median percent decrease during the last year of treatment occurs in patients with secondarily generalised seizures at baseline – at three years, seizure reduction is 87.96% and at four years is 100%.

“We are proud to share these data on the use of perampanel to manage partial-onset seizures and primary generalised tonic-clonic seizures, both seizure types with life-limiting outcomes where treatment with perampanel can make a real difference, Eisai is committed to the exploration of effective treatments for people affected by epilepsy,” comments Neil West, Vice President, Global Neurology Business Unit, Eisai EMEA.

A sub-group analysis of another Phase III trial shows that rufinamide demonstrates favourable efficacy as adjunctive treatment for adults with Lennox-Gastaut syndrome (LGS), a severe and rare form of childhood-onset epilepsy, which affects nearly 208,000 people in Europe Median change from baseline in seizure frequency was -31.5% for rufinamide (n=21) versus +22.1% for placebo (n=21), this represents a statistically significant difference in favour of rufinamide (p=0.008).

Further data reported at AAN 20169 in 138 people with LGS aged 4-37, shows no evidence of tolerance to rufinamide during short-term and long-term treatment.    Larger median decreases in both total and tonic-atonic seizure frequency for rufinamide versus placebo are evident as early as two weeks and over the course of treatment for rufinamide (total: -20.6%−-43.1%; tonic-atonic: -22.8%−-50.3%) than for placebo (total: 1.3%−-1.5%; tonic-atonic: -1.3%−1.0%), which suggests a fast onset of action and lack of short-term tolerance to rufinamide.

Rufinamide efficacy continues up to three years.  Over the course of open-label treatment from 3-36 months, progressive median decreases in seizure frequency for total seizures are -31.6% to -79.3% and for tonic-atonic seizures are -41.9% to-76.1%.9

Rufinamide is currently indicated for adjunctive treatment of seizures associated with Lennox-Gastaut Syndrome in children four years and older. Effective Lennox-Gastaut Syndrome management and compliance to treatment is of key importance to patients, as the condition is characterised by a high number of seizures - up to 70 seizures a day.  The condition often persists into adulthood and most people with this condition will have developmental delay, mental retardation, and moderate to severe learning disabilities, in addition to physiological and behavioural problems.

The development of perampanel and rufinamide demonstrates Eisai’s commitment to the therapeutic area of epilepsy and further exemplifies the company’s contribution to addressing the diversified needs of and increasing the benefits provided to patients and their families as shown by its human health care mission.