Many fonts have been spilled in recent months about the popularity of orphan drugs for big and small pharma and biotechs. The titles of articles alone are enough to give any pharma executive an anxiety attack if he or she has not already evaluated their orphan drug pipeline (from Make Mine Rare in 2011 to Orphan Drugs: Small is the New Big in 2012 to Orphan Drugs are Hot most recently in 2013, just for example). So no question, orphan drugs and rare diseases were among the hottest topics for pharma in 2012 and going into 2013.
In light of that, last year I wrote about the four things that we, the rare disease community, want from (big) pharma. John LaMattina, former president of Pfizer R&D and now a contributor to Forbes, picked up where I left off and provided his commentary on it in How Committed is Big Pharma to Rare Diseases?
Companies were seriously recognizing the potential for growth, profit, and even some image-changing compassion in rare disease. In fact, I was tracking no less than 7 companies (and countless academics) with treatments for Hunter Syndrome expressly or encompassed in their pipeline. With so many rare diseases without a treatment at all, that is some serious competition for one ultra rare disease!
What I didn’t anticipate, however, were circumstances where a treatment was obvious but big pharma specifically did not want to enter our treatment arena.
I am certainly not a crystal ball, because that is just what we have now.
Janssen Pharmaceuticals, a company of Johnson & Johnson, has a product called Elmiron, also known as pentosan polysulfate sodium or PPS. PPS has been FDA approved since 1996 for the treatment of interstitial cystitis, a painful bladder condition. PPS has also been used to treat osteoarthritis in humans as well as in horses and other animals for quite some time.
At some point, scientists began studying PPS for the use in other forms of human tissue inflammation, specifically for the inflammation that occurs in the Mucopolysaccharidosis (MPS) disorders. Specifically, Dr. Calogera Simonaro and her colleagues at Mount Sinai School of Medicine in New York began research which culminated in the publishing of Pentosan Polysulfate: A Novel Therapy for the Mucopolysaccharidoses in January 2013.The succinct and clear conclusion of the article said it best, “We conclude that PPS could be a simple and effective therapy for MPS that might provide significant clinical benefits alone and in combination with other therapies.” Specifically, the article notes that “elevated levels of several serum inflammatory markers in the MPS VI rats were reduced to near normal levels” and improved mobility, alertness, grooming, and appearance were observed. The list goes on to note improvements in the rats’ trachea, femurs, vertebrae, and dentition. Highly increased motility was hypothesized to be due to a decrease in pain, thus allowing for more movement. And finally, the article goes on to mention the possibility of positive neural effects from the drug by reducing the inflammation in the brain.
Obviously, one would understand that this research, when finally reported at conferences in 2012 and published in 2013, was extremely exciting for MPS families. The images accompanying the article showed such noticeable effects and displayed significant reversal of bone and joint disease.
So most would say, “How exciting, let’s get a clinical trial going!”
But there’s a lot more to it than that.
Some others would say, “Great! It’s already FDA approved and now we have research to support its use in MPS so we’ll just get a doctor to prescribe it for us off label! No problem.”
Not so fast.
Here is why you would want a new clinical trial for a new and wholly unrelated treatment indication as opposed to random, off-label prescriptions.
1. Understanding of efficacy: A clinical trial is the only way to understand true efficacy. Various patients with different starting points, no baseline or follow-on testing, no x-rays, and possible wide variability in dosing will prevent understanding of treatment effect. The MPS community should look no farther than its wide use of the genistein isoflavone to see that broad community off-label use provides no easy answers.
2. Tracking of adverse events: Any ill effect, especially a substantial one, outside of a clinical setting could create cause for alarm. Patients in a clinical setting are more closely monitored and must operate within certain guidelines to minimize this potential. Again, the MPS community should look no farther than the unfortunate death of Spencer Holland, even itself within a clinical trial setting, to understand the repercussions of an incredible loss connected with an experimental drug, whether or not causally connected.
3. Availability: It can be incredibly difficult to get physicians to be the first to prescribe a drug off-label, especially in this case, where it’s wholly-unconnected-off-label. So, getting a physician on-board, and then, covering the cost of a drug. An insurer could easily challenge this use as an experimental one given there is no data for its use in humans to treat MPS. And those are the challenges just in the U.S. It is likely that without a clinical trial, the drug would be wholly unavailable in many countries and/or not provided under governmental health plans.
4. Long-term and child safety data: Given that its original indication (interstitial cystitis), patient population (greater than 16 years), and treatment course (generally not long-term) are not similar to an MPS population of mostly children for long-term use, there is no human data that is relatively comparable. There is some long-term data, but it is in otherwise healthy adults. It is not difficult to see why a physician might have significant qualms being responsible for prescribing Elmiron to, say, a five-year old MPS VI patient.
5. Competitive position: Now that the possibility of a relatively inexpensive treatment exists, one shouldn’t be surprised that other parties are considering reformulating PPS into a more mainstream “orphan drug” in order to take advantage of the benefits of the Orphan Drug Act and the high pricing of rare disease drugs. Several of the article authors have, in fact, filed a patent for the use of PPS in MPS disorders. Although the patent for Elmiron ran out in 2010, Janssen has been building a virtual wall against generics by filing a Citizen Petition challenging the FDA to require bioequivalence studies of any potential generics, and the FDA has now issued such draft guidance.
Given those points, it’s not difficult to see why all parties would want a clinical trial. The MPS families sure do. In fact, Dr. Simonaro’s research was funded in part by the MPS Society and The Isaac Foundation, founded by Andrew and Ellen McFadyen, parents to Isaac, a lovely 9-year old boy suffering from MPS VI or Maroteaux-Lamy Syndrome.
However, we have learned from Mr. McFadyen that, despite those circumstances, Johnson & Johnson has consistently refused to perform a clinical trial to evaluate the use of Elmiron to treat the MPS conditions. However, if someone independently paid for and performed a trial, they would surely be in supportive of that.
Well sure, if someone else has already funded the basic research, then funds the trial, we think it would be more than dandy to cash in at that point….
And let me postulate why.
For all the good feelings associated with treating and curing kids and other laughing and smiling faces of rare and terrible diseases, in the end, it comes down to money.
Despite the fact that the R&D costs from Elmiron have long been recouped, pharma companies have become used to the receipt of high market prices for orphan drugs. As I wrote in Why I Fear the Bubble, part 1: The High Price of #RareDisease Drugs, it has become the practice for pharma companies to price orphan drugs at a high price for many legitimate reasons such as recoupment of R&D and a reasonable profit since they are only selling to a very small population.
However, in this circumstance, the R&D costs from Elmiron have long been recouped and the drug has already been priced so there is little incentive for Johnson & Johnson to perform a clinical trial other than a likely meager profit based on an already priced, relatively inexpensive drug (as far as orphan treatments go), and the compassion with which they tout their image.
One might offer a position for Janssen and Johnson & Johnson that maybe they’re not responsible for funding a trial for every rare disease that needs treatment? No, they’re not.
But when you have a drug that has clear research behind it as being able to treat a rare disease and yet, the company refuses to begin a clinical trial with no other apparent rationale than a profit motive, yes, Houston, we have a problem.
Of course companies need to make a profit, but drugs have been re-priced for rare diseases, and given that the only costs are going forward ones, J&J should be able to budget the outlay and price the market. A company truly dedicated to caring, compassion, and families, would see this data and meet these families and not only be willing to perform a clinical trial, but be excited about the possibilities of what this research can do.
Families affected by the decision of Johnson & Johnson not to fund a trial have taken to social media to show their displeasure and corral their support. The not-so-subtle ShameonJNJ.com tells the story of many children whose families are interested in such a clinical trial and allows others to add their stories. Families are also tweeting to @JNJNews, @JNJCares, and @JNJParents and also with the hashtag #shameonjnj.
This is an issue to watch.
Updated on 3/2/2013 to reflect a change in Johnson & Johnson’s Twitter handles from @JNJComm to the ones noted above. The changes appeared to have occurred on March 1, 2013 after a social media blitz orchestrated by The Isaac Foundation, other MPS families, and their supporters surrounding Rare Disease Day, February 28. The author has no way of knowing whether the blitz was the impetus for the changes or whether they occurred by coincidence.
Copyright © 2013, Melissa Hogan. All rights reserved.