Ruzurgi (amifampridine, also called 3,4-diaminopyridine or 3,4-DAP) is the first treatment approved by the U.S. Food and Drug Administration (FDA) to treat Lambert-Eaton myasthenic syndrome (LEMS) in patients from ages 6 to 16.

Ruzurgi was developed by Jacobus Pharmaceuticals and is now licensed by Catalyst Pharmaceuticals, which also has licensing rights for the development and commercialization of Firdapse, an approved formulation of amifampridine to treat patients 17 and older.

The two medications contain slightly different formulations of amifampridine. Firdapse contains amifampridine phosphate, which is more stable than the formulation in Ruzurgi.

What is LEMS?

LEMS is a rare autoimmune disease in which the immune system generates autoantibodies against a protein called voltage-gated calcium channel (VGCC) in the nerve cell endings.

Normally, when the brain sends a nerve signal to muscles, the signal is sent as a depolarization of the nerve cells: ions flood in and out of the nerve cell, changing the ratio of charged particles in the cell, and thus, its electrical charge.

When this depolarization reaches the neuromuscular junction or the point where the nerve cell and muscles meet, this electrical signal is converted into a chemical signal; when the charge reaches the VGCC, the channel opens, allowing calcium to enter the nerve cell and cause the release of acetylcholine (a neurotransmitter or cell signaling molecule) into the neuromuscular junction.

Acetylcholine binds to its receptors on the other side of the junction, initiating a cascade of events that makes the muscles move. After the nerve signal has been sent, voltage-gated potassium channels on the nerve cell open and “reset” the nerve, which closes the VGCC, stopping the flow of calcium into the nerve cell and preparing it for the next signal from the brain.

In LEMS, nerve cells have many fewer VGCC molecules as a result of the attack by the immune system, meaning that little acetylcholine is released in response to nerve signals. Without sufficient stimulation from the nerve cells, muscles weaken over time.

How does Ruzurgi work?

Ruzurgi contains a small molecule (amifampridine) that binds to the voltage-gated potassium channels. By blocking these channels, Ruzurgi prevents the nerve cell from resetting after a nerve signal has been sent, and gives the nerve cell more time for the small number of VGCCs that remain to stay open. Even with fewer channels, the increase in calcium transported can increase the amount of acetylcholine that’s released from the nerve cell endings, and thereby increase muscle strength.

Ruzurgi in clinical trials

The decision to approve Ruzurgi for children with LEMS was based on clinical data collected from adult patients, combined with simulations to find the best dose for children. The data were collected from a Phase 2 clinical trial (NCT01511978) called DAPPER. The trial included 32 adult LEMS patients who had been taking Ruzurgi for at least three months as part of an FDA-approved compassionate use program. Patients were randomly assigned to either continue treatment with Ruzurgi at a dose of 30 to 100 mg daily (divided into three doses) or to a placebo.

The results of the trial were evaluated using the triple timed-up-and-go (3TUG) test, which measures the time it takes a patient to rise from a chair, walk a short distance, and return to the chair three times without pause. The results showed that patients who remained on Ruzurgi were able to perform the tasks in less time than those who were taking the placebo.

Additional information

Ruzurgi may cause serious side effects, including seizures and allergic reactions. The most common side effects are stomach pain, indigestion, dizziness, and nausea.

 

Last updated: Oct. 30, 2019

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Lambert-Eaton News is strictly a news and information website about the disease. It does not provide medical advice, diagnosis, or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.

Emily holds a Ph.D. in Biochemistry from the University of Iowa and is currently a postdoctoral scholar at the University of Wisconsin-Madison. She graduated with a Masters in Chemistry from the Georgia Institute of Technology and holds a Bachelors in Biology and Chemistry from the University of Central Arkansas. Emily is passionate about science communication, and, in her free time, writes and illustrates children’s stories.
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Özge has a MSc. in Molecular Genetics from the University of Leicester and a PhD in Developmental Biology from Queen Mary University of London. She worked as a Post-doctoral Research Associate at the University of Leicester for six years in the field of Behavioural Neurology before moving into science communication. She worked as the Research Communication Officer at a London based charity for almost two years.
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Emily holds a Ph.D. in Biochemistry from the University of Iowa and is currently a postdoctoral scholar at the University of Wisconsin-Madison. She graduated with a Masters in Chemistry from the Georgia Institute of Technology and holds a Bachelors in Biology and Chemistry from the University of Central Arkansas. Emily is passionate about science communication, and, in her free time, writes and illustrates children’s stories.
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