Ruzurgi (amifampridine) for the treatment of LEMS

Ruzurgi (amifampridine) is a potassium channel blocker indicated for the treatment of Lambert-Eaton myasthenic syndrome (LEMS) in paediatric patients. Image courtesy of DFliyerz.

LEMS is an autoimmune disease that destroys the neuromuscular junctions of the body. Image courtesy of Doctor Jana.

Ruzurgi is available as 10mg white-to off-white tablets for oral administration. Image courtesy of Zacharmstrong.

Ruzurgi (amifampridine) is approved for the treatment of Lambert-Eaton myasthenic syndrome (LEMS) in paediatric patients.

The drug was initially developed as a phosphate salt of amifampridine by Assistance Publique Hôpitaux de Paris. It was later developed and commercialised by various companies, including BioMarin Pharmaceutical, Catalyst Pharmaceuticals and Jacobus Pharmaceutical.

Jacobus submitted a new drug application (NDA) for amifampridine to the US Food and Drug Administration (FDA) in June 2018 and received a priority review designation. The FDA approved the drug in May 2019. The FDA also granted orphan drug and fast track designations.

Ruzurgi contains 3,4-diaminopyridine phosphate (DAPP) as an active compound, which is a white, soluble crystalline powder. The drug is available as an oval, functionally scored, white to off-white tablet in 10mg strength.

Jacobus is responsible for the manufacturing and commercialisation of the drug for the treatment of LEMS in patients aged from six to 17 years.

Catalyst Pharmaceutical markets a similar drug in the US, which BioMarin Pharmaceutical markets in Europe under the brand name Firdapse^® for the treatment of LEMS in adult patients aged 18 years or more.

LEMS causes and symptoms

LEMS is a rare autoimmune disease that attacks the neuromuscular junctions of the body. It destroys the nerve cells’ ability to send signals to the muscle cells. LEMS is named after two neurologists Edward Lambert and Lee Eaton, who described the disease.

LEMS is a small molecule potassium channel blocker that hinders the calcium channels on nerve endings that are responsible for releasing acetylcholine, a chemical messenger that generates muscle contraction. Reduced levels of acetylcholine cause improper muscle contraction, weakening the muscles.

Patients suffering from cancers are susceptible to the condition, which can affect individuals of any age. Three in every one million people worldwide are affected.

Some common symptoms associated with the disease are weakness in the legs, hip, upper arms, eye muscles and shoulders, as well as difficulty walking, talking.

Clinical trials on Ruzurgi

The FDA’s approval of the drug was based on the positive results of a Phase II, randomised, double-blind, placebo-controlled, withdrawal study named DAPPER. The study enrolled 32 adult patients who were already receiving Ruzurgi for three months prior to being enrolled in the clinical study.

Patients continuing with Ruzurgi were compared with those that switched to placebo on beginning the trial. The primary endpoint of the study was the degree of change in the Triple Timed Up and Go test (3TUG) after the withdrawal of the drug.

3TUG is the amount of time taken by patients to rise from a chair, walk for 3m and return to the chair three times consecutively. Higher scores suggest greater deterioration.

Patients administered with Ruzurgi did not witness more than 30% deterioration in the final round of the 3TUG test, while 72% of patients randomised to placebo experienced more than 30% deterioration in the final 3TUG test.

The most common adverse events reported during the clinical trial were burning or prickling sensations, abdominal pain, dyspepsia, dizziness and nausea.