Lambert-Eaton Myasthenic Syndrome (LEMS) is a rare problem that affects your nerves and muscles. With LEMS, your immune system mistakenly attacks the place where your nerves and muscles connect. This damages nerve endings, reduces the amount of acetylcholine (a chemical that helps nerves and muscles communicate), and keeps your muscles from working properly. It can cause severe muscle weakness and tiredness that is progressive (gets worse over time). Firdapse (amifampridine) is an FDA-approved treatment for LEMS.
What Tools Were Used in the Studies for Lambert-Eaton Myasthenic Syndrome (LEMS)?
Before describing how Firdapse was studied, it is important to understand the tools that were used in the studies. There were three main tools used in the studies that looked at how well Firdapse works for people with LEMS. Each tool is briefly described below:
Quantitative Myasthenia Gravis (QMG) score. Health care providers examine the 13 QMG items and assign each item a score using a 4-point scale, ranging from 0 (no weakness) to 3 (severe weakness). These numbers are added up to get the QMG score. Lower QMG scores indicate less muscle weakness, while higher scores signal more weakness.
Subject Global Impression (SGI) score. People who were enrolled in the studies used a 7-point scale to rate how the study medicine affected their overall physical well-being. Lower scores correlate with people in the study perceiving less benefit from the study medicine, while higher scores indicate more perceived benefit from the study medicine.
Clinical Global Impression Improvement (CGI-I) score. Health care providers use a 7-point scale to rate the change in a study participant’s symptoms. Lower scores indicate that symptoms improved with the medicine, while higher scores indicate that symptoms worsened.
How Was Firdapse Studied for Lambert-Eaton Myasthenic Syndrome (LEMS)?
Most studies that assess how well a medicine works for a specific condition look at how symptoms or disease markers change with the medicine. The studies that looked at using Firdapse for LEMS did things a bit differently. These studies checked if symptoms got worse when Firdapse was stopped. Two main studies looked at Firdapse for LEMS.
Study 1 started with 38 people with LEMS (84% had autoimmune LEMS, and 16% had paraneoplastic LEMS). The people in this study ranged in age from 21 to 88 years. About 61% of the people in study 1 were women, and most people were White (90%). Race information for the other people in the study was not provided. There was an open-label run-in phase where everyone in the study took Firdapse, and everyone knew they were taking Firdapse. At the end of the open-label run-in phase, QMG, SGI, and CGI-I scores were measured for everyone in the study. Then the 38 people were divided into two groups. During this part of the study, neither the people in the study nor the study investigators knew who was taking Firdapse and who was taking a placebo (no medicine in it). Sixteen of the 38 people continued to take Firdapse. Twenty-two of the people slowly switched from Firdapse to a placebo over seven days. For the next seven days, people in the study continued taking Firdapse or a placebo. Then QMG, SGI, and CGI-I measurements were repeated.
Study 2 started with 26 people who were taking a stable dose of Firdapse. People who had recently taken certain medicines, including azathioprine, cyclosporin, immunoglobulin G, mycophenolate, or rituximab, or those who had recently received plasmapheresis, were not eligible to be in the study. The people ranged in age from 31 to 75 years with an average age of 54 years. About 62% of the people were women, and most people were White (88%). One person was African American, and the race of two people was not provided. People in the study were allowed to keep taking stable doses of certain medicines, such as cholinesterase inhibitors or corticosteroids. Baseline QMG and SGI scores were measured. Then, half of the people in the study (13 people) continued taking Firdapse. The other half (13 people) changed from Firdapse to a placebo (no medicine) for four days. Neither the people in the study nor the study investigators knew who was taking Firdapse and who was taking a placebo. After four days, QMG and SGI measurements were repeated.
What Benefits Were Seen?
The results of study 1 and study 2 are presented in the tables below.
| Study 1 | Firdapse | Placebo |
| QMG Scores | ||
| Baseline | 6.4 | 5.6 |
| Change* | 0.4 | 2.2 |
| Difference* | -1.7 | |
| SGI Scores | ||
| Baseline | 5.6 | 5.9 |
| Change* | -0.8 | -2.6 |
| Difference* | 1.8 | |
*These data are based on calculations that adjust for differences between groups, known as least squares (LS) means. It is another way to compare results and may give a more accurate comparison than raw data.
| Study 2 | Firdapse | Placebo |
| QMG Scores | ||
| Baseline | 7.8 | 8.5 |
| Change* | 0 | 6.54 |
| Difference* | -6.54 | |
| SGI Scores | ||
| Baseline | 6.1 | 5.8 |
| Change* | -0.64 | -3.59 |
| Difference* | 2.95 | |
*These data are based on calculations that adjust for differences between groups, known as least squares (LS) means. It is another way to compare results and may give a more accurate comparison than raw data.
Studies 1 and 2 also looked at CGI-1 scores. CGI-I scores were higher in people who took a placebo. This means that health care providers saw a greater worsening of symptoms in people who took a placebo instead of Firdapse than in people who continued taking Firdapse.
Overall, in two studies, both people and health care providers noted that LEMS symptoms seemed to get worse, and people’s overall sense of physical well-being seemed to decline when Firdapse was stopped, compared with continued Firdapse use. It is important to note that your results may differ from what was seen in clinical studies.
How Do I Take Firdapse?
Firdapse is a tablet that you swallow. It can be taken with or without food. If you have trouble swallowing tablets, need to use a feeding tube, or take a dose of Firdapse that is lower than 5 mg, you can use the tablets to make a liquid that can be given through a feeding tube or by mouth using an oral syringe. There are detailed directions about how to make the suspension in the “Instructions for Use” section of the product information. If you make a liquid out of Firdapse tablets, you will need to make it every day and store it in the refrigerator. Throw away any liquid that is not used within 24 hours of making it.
Firdapse is taken several times a day, usually about three to five times a day. When you first start taking it, you will start on a low dose. Your health care provider will give you instructions on how often to increase the dose (usually every three or four days) and by how much (usually between 2.5 and 5 mg). Do not change your dose on your own, and follow the dosing instructions from your health care provider.
Adults should not take more than 20 mg at a time, and children weighing less than 45 kg (99 pounds) should not take more than 10 mg at a time.
How Can I Prevent and Manage Side Effects?
Seizures are one of the possible rare but serious side effects of Firdapse. If you have ever had a seizure before, you should not take Firdapse. Tell your health care provider about your full medical history and any medicines that you take.
Your risk for seizures may be higher if you have certain medical conditions or take certain medicines. Your risk may also be higher if you take a higher dose of Firdapse. Do not increase your dose without your health care provider telling you to do so.
If you have a seizure while taking Firdapse, tell your health care provider right away. Your health care provider may stop the medicine entirely or lower your dose.
What Kinds of Drug Interactions May Happen?
Drug interactions can be complicated. Sometimes, one medicine can affect the level of another medicine in your blood. Higher medicine levels can increase side effects, while lower medicine levels can lessen its ability to work.
Other times, medicines can affect your body in a way that can make a side effect of another medicine more likely. Some medicines can lower your body’s seizure threshold, which means they make your brain a little more likely to have a seizure than it normally would. Seizures are a rare, but possible side effect from Firdapse, so it is important for your health care provider to know about all of your medicines before and while taking Firdapse.
Is There Any Cost Assistance Available for Firdapse?
A cost assistance program is available through the company that makes Firdapse. It may reduce the amount you pay. Whether you qualify to enroll may depend on what type of insurance you have or if you are uninsured.
Visit this website from the drugmaker for more information about Firdapse costs and copay savings. You can also call 833-4-CATALYST (833-422-8259) to contact a representative for financial support information and other resources.
