GSK and XenoPort receive FDA approval for Horizant® for postherpetic neuralgia

GlaxoSmithKline plc (GSK) and XenoPort, Inc. (Nasdaq: XNPT) announced today that the United States (US) Food and Drug Administration (FDA) has approved Horizant® (gabapentin enacarbil) Extended-Release Tablets for the management of postherpetic neuralgia (PHN) in adults.

The efficacy and safety of Horizant for the management of PHN was evaluated in a single 12-week principal efficacy trial, plus two supportive studies that all met their respective primary endpoints. The three clinical studies involved 574 adult patients from the US, Canada and Germany.

The recommended dosage for the management of PHN in adults is 600 mg twice daily. Treatment should be initiated at a dose of 600 mg in the morning for three days followed by 600 mg twice daily (1,200 mg/day) beginning on day four. Doses must be adjusted in patients with impaired renal function. In the 12-week, controlled study in patients with PHN, somnolence and dizziness were the most frequently reported side effects. Somnolence was reported in 10% of patients treated with 1,200 mg of Horizant per day compared with 8% of patients receiving placebo. Dizziness was reported in 17% of patients receiving 1,200 mg of Horizant per day compared with 15% of patients receiving placebo.

In association with GSK’s first commercial sale of the product after approval for PHN, XenoPort is entitled to a milestone payment of $10 million from GSK.

About Horizant

Horizant is not approved or licensed outside the US for PHN. It was approved for the treatment of moderate-to-severe primary Restless Legs Syndrome (RLS) in adults in the US on 6th April 2011. It is not recommended for RLS patients who need to sleep during the day and remain awake at night. Please see Important Safety Information below and the complete prescribing information available at www.gsk.com.

Discovered and developed by XenoPort, gabapentin enacarbil utilises the body’s nutrient transport mechanisms that are believed to facilitate its absorption into the body. Once absorbed, it is converted into gabapentin, which binds to a specific type of calcium channel but does not exhibit affinity for other common receptors. The exact mechanism of action of the compound in treating RLS or managing the symptoms of PHN is unknown.

Horizant is not interchangeable with other gabapentin products because of differing pharmacokinetic profiles. The same dose of Horizant results in different plasma concentrations of gabapentin relative to the same dose of other gabapentin products.

Important Safety Information for Horizant (gabapentin enacarbil):

Effects on Driving

• Horizant causes significant driving impairment. Patients on Horizant should not drive until they have sufficient experience to know whether their ability to drive is impaired. The patients’ ability to assess their driving competence and their ability to assess the degree of somnolence caused by Horizant can be imperfect.

Somnolence/Sedation and Dizziness

• Horizant causes somnolence/sedation and dizziness. Patients should not drive or operate other complex machinery until they have sufficient experience on Horizant to know whether their ability to perform these tasks is impaired.

Lack of Interchangeability With Gabapentin

• Horizant is not interchangeable with other gabapentin products due to differing pharmacokinetic profiles. The same dose of Horizant results in different plasma concentrations of gabapentin relative to other gabapentin products. The safety and effectiveness of Horizant in patients with epilepsy have not been studied.

Suicidal Behaviour and Ideation

• Horizant is a prodrug of gabapentin, an antiepileptic drug (AED). AEDs increase the risk of suicidal thoughts or behaviour in patients taking these drugs for any indication. As a prodrug of gabapentin, Horizant also increases this risk. Patients treated with any AED for any indication should be monitored for new or worsening depression, suicidal thoughts or behaviour, and/or any unusual changes in mood or behaviour. Anyone considering prescribing Horizant must balance the risk of suicidal thoughts or behaviour with the risk of untreated illness.

  Patients, caregivers, and families should be informed that Horizant increases the risk of suicidal thoughts and behaviour and should be advised of the need to be alert for new or worsening signs and symptoms of depression, any unusual changes in mood or behaviour, or the emergence of suicidal thoughts, behaviour, or thoughts of self-harm. Behaviours of concern should be reported immediately to healthcare providers.

Drug Reaction With Eosinophilia and Systemic Symptoms (DRESS)/Multiorgan Hypersensitivity

• Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), also known as multiorgan hypersensitivity, has been reported in patients taking antiepileptic drugs, including gabapentin. Horizant is a prodrug of gabapentin. Some of these events have been fatal or life-threatening. DRESS typically, although not exclusively, presents with fever, rash, and/or lymphadenopathy, in association with other organ system involvement, such as hepatitis, nephritis, hematological abnormalities, myocarditis, or myositis sometimes resembling an acute viral infection. Eosinophilia is often present. Because this disorder is variable in its expression, other organ systems not noted here may be involved.

Discontinuation of Horizant

• In patients with PHN receiving Horizant twice daily, reduce the dose to once daily for one week prior to discontinuation to minimise potential for withdrawal seizure.

Adverse Reactions

• The most common adverse reactions for Horizant 1200 mg/day and placebo, respectively, in the PHN principal efficacy study were dizziness (17% and 15%), somnolence (10% and 8%), headache (10% and 9%), nausea (8% and 5%), and fatigue/asthenia (6% and 1%).

About Postherpetic Neuralgia

Postherpetic neuralgia is a neuropathic (nerve) pain syndrome that may result in disability in some people. PHN follows the healing of an outbreak of herpes zoster, commonly known as shingles. Approximately one million people in the US develop shingles each year. Of these, approximately ten percent develop PHN.