- The Elmiron controversy is a key example of why longterm clinical drug testing is so important for the safe use of the drug
Elmiron has recently been the subject of a number of lawsuits brought about over claims that the drug causes vision problems and may lead to blindness. The drug (pentosan polysulfate sodium) is an oral medication prescribed for interstitial cystitis, which is thought to affect over 1 million Americans. Elmiron is produced in the US by Janssen Pharmaceuticals Inc, and those taking action claim that patients and doctors were not adequately informed of its risks. The controversy highlights the importance of clinical trials in the development of new drugs and the transparency of manufacturers when it comes to labeling products with potential risks.
The Elmiron lawsuits
It is not fully understood how Elmiron works, which in itself is perhaps a red flag. It is believed that it lines the mucosal layer of the bladder, preventing irritants reaching the bladder wall from the urine, but this was never confirmed before the drug was distributed. Elmiron was first approved in 1995, and Janssen Pharmaceuticals Inc has benefited from over $150 million in sales a year ever since, as it has become a common treatment for interstitial cystitis. Concern about the treatment is growing, however, with Elmiron lawyers reviewing an increasing number of cases involving severe side effects relating to vision. Patients who have experienced these severe side effects could now be entitled to compensation for Elmiron eye damage.
A common complaint amongst those who have experienced severe side effects has been maculopathy, which is notoriously difficult for patients to recognize. Symptoms include image distortion, difficulty adjusting to darkness, the appearance of a blindspot, and difficulty focusing on objects. The manufacturers did not originally warn of maculopathy as a potential side effect, but with the rising number of lawsuits against the company, Janssen Pharmaceuticals Inc have now changed warning labels to include a risk of ‘retinal pigmentary changes.’
Warnings came too late
For many patients, this change in labeling has come too late. Some doctors may not have prescribed the medication for at-risk patients if the risk had been highlighted sooner. While trials were conducted for Elmiron, it is clear that more could have been done before the medication was distributed. One study, conducted since its release, found indisputable signs of drug toxicity in 22 patients in a sample of 91, and a number of case studies have shown a correlation between Elmiron and maculopathy.
Effective clinical trials should confirm that a drug works well and test for all potential side effects. Until comprehensive trials are undertaken, there is not enough evidence to show that a drug is safe or effective, and this puts patients at risk. Randomized clinical trials (RCTs) are generally regarded to be the best way of comparing treatments, but each step of the trial process is critical in order to ensure that only safe medication is approved. Many of the signs of maculopathy in Elmiron users were not seen until after three years of use, highlighting the need for long-term trials before medication is deemed safe.
Was Elmiron’s testing flawed?
Part of the difficulty in the Elmiron case is that the drug was subject to testing before it was approved by the FDA, and therefore, no rules were broken. Elmiron was tested in 2,627 patients over the course of two trials. By the time of the second trial, however, 52% of the subjects had either dropped out of the test or were no longer eligible. This highlights one flaw in the system: there must be measures in place to adequately test any medication even if the original cohort is no longer available for testing.
In these original trials, it was seen that Elmiron relieved the pain affecting many patients within three months. For others, the pain was not reduced for six months. While pain relief did eventually reach these patients, it could be argued that a medication that takes six months to show effect should undergo further development. This is highlighted by the fact that another study published in the Journal of Urology found that pentosan polysulfate sodium taken orally provided little benefit to most interstitial cystitis patients.
Side effects seen in the original trials
In the original trials, most of the side effects associated with Elmiron were minor. However, out of the 2,627 strong sample, 33 patients did experience serious side effects. Six patients died, but it was concluded that this was caused by other health issues.
The most common side effects were seen in 1-4% of the patients. One of these was alopecia, which began in the first four weeks of using the medication. Approximately 97% of participants lost hair in one place, which usually grew back once the drug was stopped. The other most common side effects were nausea, diarrhea, a rash, headaches, abdominal pain, stomach upset, dizziness and abnormal liver function. Some patients also experienced edema and weight gain. In a Phase 4 trial, 6.3% of patients given a daily dose of 300mg were affected by mild rectal hemorrhage. A further 15% taking a higher dose (900mg) had increased rectal bleeding. No vision problems were found in short-term use.
Adverse effects listed over time
By 2019, 2,460 adverse side effects were listed on the FDA Adverse Event Reporting System (FAERS) for Elmiron. 1,691 of these voluntary reports were serious, and 23 deaths were listed. However, while this does seem alarming, the FDA can’t confirm that these effects were related to the use of Elmiron, as this is not evidence from clinical testing; it is simply voluntary data. Nonetheless, this data is significant.
The clinical trials for Elmiron found side effects in patients over the course of the first year of drug use. However, for the majority of patients who have developed maculopathy, side effects were not seen until after at least three years of use. Clinical testing that does not study long-term side effects is arguably inefficient, and whether a drug should be approved so quickly after short-term trials is questionable.
It is clear that Elmiron has some benefits for interstitial cystitis patients. However, the study of potential side effects is as important as the study of a medication’s effectiveness, and the Elmiron controversy highlights the need for trials to take place over a number of years in order to identify all potential risks. Clinical trials are vital in the development of any new treatment, but it’s important that they are comprehensive enough to mitigate the risk to patients after long-term use.
