Methods of treating lennox-gastaut syndrome using fenfluramine

Abstract

A method of treating and / or preventing symptoms of Lennox-Gastaut Syndrome (LGS) also known as Lennox Syndrome in a patient such as a patient previously diagnosed with Lennox Syndrome, by administering an effective dose of fenfluramine or its pharmaceutically acceptable salt to that patient. Lennox Syndrome patients are treated at a preferred dose of less than about 2.0 to about 0.01 mg / kg / day.

Description

FIELD OF THE INVENTION[0001]This invention relates generally to the field of methods of treatment and in particular, methods of treating human patients, and more particularly towards treating human patients diagnosed with Lennox-Gastaut Syndrome.BACKGROUND OF THE INVENTION[0002]This invention relates to the treatment of symptoms of Lennox-Gastaut Syndrome (“LGS,” sometimes referred to as “Lennox Syndrome”) using an amphetamine derivative, specifically fenfluramine.[0003]Fenfluramine, i.e. 3-trifluoromethyl-N-ethylamphetamine is an amphetamine derivative having the structure:[0004]Fenfluramine was first marketed in the US in 1973 and had been administered in combination with phentermine to prevent and treat obesity. However, in 1997, it was withdrawn from the US and global market as its use was associated with the onset of cardiac valve fibrosis and pulmonary hypertension. Subsequently, the drug was withdrawn from sale globally and is no longer indicated for use in any therapeutic ar...

AI Technical Summary

Benefits of technology

[0099]FIG. 1 is a table summarizing the procedures followed during each of the patient visits which are conducted over the course of the clinical trial described in Example 1.

[0100]FIG. 2 is a flow chart illustrating the manner in which fenfluramine dosages are increased for non-responding patients over the course of the clinical trial.

Problems solved by technology

However, in 1997, it was withdrawn from the US and global market as its use was associated with the onset of cardiac valve fibrosis and pulmonary hypertension.

One disorder for which new treatment options are sorely needed is epilepsy, and in particular, epilepsy syndromes which are refractory to known treatments.

Prior to the inventor's work, investigation of fenfluramine's efficacy in epilepsy patients, while showing some initial promise, was far from definitive, and shared a common paradigm, i.e., that fenfluramine's primary effects were on behaviors that caused or induced seizures, not treating or preventing the seizure itself.

However, the authors did not attribute fenfluramine's efficacy to generalized anti-seizure activity.

That is, while a particular drug may be effective against one form of epilepsy, it may be wholly ineffective against others, or even contra-indicated due to exacerbation of symptoms, such as worsening the frequency and severity of the seizures.

As a result, efficacy of a particular drug with respect to a particular type of epilepsy is wholly unpredictable, and the discovery that a particular drug is effective in treating in treating a type of epilepsy for which that drug was not previously known to be effective is nearly always surprising, even in cases where the drug is known to be effective against another epilepsy type.

LGS is characterized by frequent seizures and different seizure types; it is typically accompanied by developmental delay and psychological and behavioral problems.

Further, most patients have atonic seizures, also called drop seizures, which cause their muscles to go limp and result in the patient suddenly and unexpectedly to fall to the ground, often causing significant injury, which is why patients often wear a helmet to prevent head injury.

Diagnosis may be difficult at the onset of the initial symptom(s) because the triad of features associated with LGS, such as tonic seizures, may not be fully established, and EEG during sleep is required to confirm the condition.

Many different treatments are currently used in the treatment of this disorder and many more have been tried in the past, most often with little success.

A variety of therapeutic approaches are currently used in LGS, including conventional antiepileptic medications, diet and surgery, however the evidence supporting these therapies is not robust and treatment remains most often ineffective.

Despite the severity of LGS's symptoms and the frequency with which it occurs (it accounts for up to 10% of all childhood epilepsies), there is currently no standard evidence-based treatment for the disease.

The authors concluded that there is a paucity of research and “ .

The authors further concluded that “[t]he optimum treatment for LGS remains uncertain and no study to date has shown any one drug to be highly efficacious”.

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