Editorial Note: This post follows on from one of the most compelling RxISK stories ever – Abilify, Tourette Syndrome and Me, posted last week. It comes in two parts. The first by last week’s author and the second by the series editor, Johanna Ryan.
In our efforts to get our story told, raise awareness about the dangers of antipsychotics, and fight for better treatments for Tourette’s Syndrome and its associated conditions, it was important to get our voice heard at the FDA. When we first discovered that a clinical trial called the Archer Study was seeking FDA approval of Abilify for the treatment of Tourette Syndrome, we were horrified and realized that we had to do something to stop it! This was the very drug that disabled me and made us realize just how awful the treatments for TS are!
This study was particularly unsettling because it was sponsored by the manufacturer itself (Otsuka Pharmaceuticals). It was a shameful hot mess because it appeared that Otsuka wasn’t familiar enough with their own product, let alone Tourette’s, to even recognize that there were serious problems. As we would tell the FDA, when comparing how TS was categorized in the study vs. Abilify’s Prescribers Guide, it was unclear if Otsuka could even decide if they thought tics were a neurological or a mental illness.
We spent a year of our lives gathering information and writing a letter to the FDA in an effort to stop their approval of Abilify for the treatment of Tourette Syndrome. We were asking the FDA to investigate the Archer Study for possible negligence and lack of informed consent of their research subjects. We were also requesting that the FDA determine that TS, OCD and ADHD are contraindications for this drug. When completed, our FDA letter was 16 pages long and it would have been even longer had we not compromised to leave items out. Especially because of my condition caused by Abilify, it became quite overwhelming for us to write this letter. There were so many negative things to write about because it is so complex with all its detrimental effects. We were really hoping the sheer content of our letter would make a statement to the FDA on just how wrong this drug is in treating TS.
We sent our letter to the Director of the Center for Drug Evaluation and Research (CDER) and a copy to the Director of ODE I. The FDA’s website is not user friendly and so locating the correct departments was a job in itself. After not hearing back from anyone at the FDA, we decided to call the ODE I office. After weeks of leaving voice messages, the secretary from ODE I finally returned our call. If not for the consideration of the ODE I office, who forwarded our letter to the Division of Drug Information, we probably would have never received any communication from them at all! It was approximately another month later when we received a response from the Division of Drug Information.
In the response that we received from the FDA, one of their only suggestions to help us was to file a report with MedWatch about our experience with Abilify. It was interesting to us because we had already filed a report with MedWatch months before we had received their letter. Almost a year later, we’re still waiting for someone to contact us concerning our report. It is also important to note when we reached out to other organizations, they too, put so much weight on us contacting MedWatch. This was even more discouraging to us since our experience with MedWatch made us feel as if this is simply a place to get your “medication story” lost in a sea of reports.
At first, we felt that our letter was well-received by the FDA because they told us that our letter was “well-written and informative,” and that they would be taking our information into account during the approval process of Abilify for TS. But they went on to say that “information about a drug or drug indication that is under FDA review and not yet approved is subject to strict confidentiality laws.”
We responded to the FDA and included even more information about why we feel Abilify is a poor choice for treating TS. Due to the confidentiality laws, it made any further communication with them impossible. Our concern is that these laws seem to be in favor of the pharmaceutical companies and not the health and welfare of patients. The current process does not seem to allow for government transparency and why a drug is or is not approved remains much of a secretive process to the public.
In our continued efforts to move our mission forward, we have also reached out to the CDC, NAMI, Tourette Syndrome Association (TSA), Yale Child Study Center (a TSA Center of Excellence), Harvard University/Massachusetts General Hospital, the First Lady and various other organizations. In the last year and a half, even with our multiple attempts to connect, many did not respond. When they did, they were confident that the FDA would be the organization to properly address our concerns. We have since realized that working with the FDA is ineffective, so we have changed our direction to focus more on educating patients and the medical community.
Otsuka filed to have Abilify approved as a treatment for children with Tourette’s in 2014, almost 12 years after its 2002 debut for schizophrenia and bipolar disorder. The FDA approved it in December 2014. Then something really bizarre took place: FDA decided the drug deserved approval for adults with Tourette’s as well – and Otsuka was outraged! It’s not often you hear of a drug company objecting to being offered a bigger market. What on earth was going on?
The answer, as explained by Ed Silverman in the Wall Street Journal and in other legal and financial blogs, was breathtaking in its cynicism. Otsuka’s move had nothing to do with the welfare of children – and didn’t even have much to do with the money to be made selling Abilify to people with Tourette’s! They were playing a highly technical game with U.S. patent law in which Tourette’s sufferers young or old were no more than pawns. The game focused on two well-meaning laws intended to give drug companies incentives to do the right thing: the Orphan Drug law, and pediatric exclusivity.
The 1985 Orphan Drug law aimed to encourage companies to develop drugs for rare diseases. Such drugs could be lifesavers for a few thousand people, but the market might be too small to be profitable. Classification as an “orphan drug” results in seven extra years of patent protection. “Pediatric exclusivity” was added to US drug law due to concerns that many drugs tested on adults were being used on children without any research into the special precautions or lower doses that children might need. A drug tested and approved for children can get three extra years of patent protection, at least for pediatric use. In some cases – and this made Otsuka’s ears perk up – the three-year extension can apply to any use of the drug, if FDA feels that putting a generic version on the market without those special instructions for pediatric use might endanger children.
So Otsuka attempted a double-whammy. It applied for orphan-drug status for Abilify as a treatment for “Tourette’s in children.” If they’d applied for Tourette’s in adults too, they could have kept generic rivals out of the Tourette’s market for seven years. Otsuka, however, then sued to block ANY generic competition for seven years, arguing that putting generic copies on the market without that patented labeling would endanger adults with Tourette’s as well as children! Its lead attorney was Ralph Tyler of Venable LLP, former lead counsel for the FDA.
At stake was the huge overall market for Abilify, which brought in $6.5 billion in the U.S. in 2013. The patent was set to expire in April 2015. Otsuka has pushed the U.S. price of Abilify to close to $1,000 a month, and the cost of this one drug has become particularly painful for state and federal programs that insure most people with severe mental illness. Otsuka had known for years that doctors were using Abilify off-label to treat Tourette’s, but had held off on seeking FDA approval. Their eleventh-hour “Tourette’s maneuver” was aimed at locking up the entire market until late 2021.
On April 28, they got their (disappointing) answer. The FDA agreed to approve Abilify only for pediatric Tourette’s. In the name of children’s safety, it granted a seven-year exclusive patent on Tourette’s in general. However, it argued there was no need to keep generic versions of Abilify off the market for other uses, as long as the makers were not allowed to label or market them for Tourette’s. Consumers on both public and private insurance will get a huge break. Hopefully we’ll all get a break from Otsuka’s aggressive marketing of Abilify, allowing us to think logically about who really needs to take it and for how long. Otsuka will have to look elsewhere to plug a huge hole in its sales.
Otsuka is not the first company to manipulate the Orphan Drug law to make megabucks. My favorite example is the Lidocaine Patch, until recently available only from Endo Pharma for $800 – $1100 per month. It was approved in 1999 as an orphan drug for post-herpetic neuralgia (“shingles”), a nerve infection that causes painful itching and burning. It was obvious this patch could be useful to lots of people with pain from injuries involving a “pinched nerve” or similar condition. By wisely refraining from seeking that approval, Endo forced people with extremely common disorders to pay through the nose for its “orphan drug.” All this from a simple reformulation of a very old medicine!
Lidocaine has been around for over fifty years – I can remember parents spraying “Solarcaine” on sunburned children in the sixties. For people with back pain, it’s clear the Patch works better and lasts longer than the lidocaine creams they could buy at the drugstore, and may help them limit their use of more harmful narcotics. It’s not clear why so many should pay more for their Patches than for their monthly rent or groceries.
Lots of other drug companies have made a killing with similar maneuvers. Approval for pediatric use produces a three-year patent extension, even for a drug like Celebrex which few children actually use. Just testing a drug on children yields a six-month extension, even if the company never files for pediatric use. Eli Lilly played that game with its antidepressant Cymbalta, despite knowing the drug was unlikely to test well in children. Lilly enjoyed the extra six months of patent protection; we don’t know how the children in the clinical trial felt.
Otsuka is extorting more than money, however. It’s pretty hard to hurt yourself with lidocaine. But the overuse and over-promotion of Abilify has already been ruinous for thousands of patients. It may be particularly risky for people with Tourette’s, although it apparently works for some. Ironically, allowing sky-high prices for Abilify in the U.S. may have helped it become far more dominant here than in the U.K. or Europe. The financial incentives to promote the drug were so huge that patients and doctors alike were bombarded with propaganda about its virtues. People like the author of this and the previous post have become pawns in this game to an even greater degree than the rest of us.
The final part of the series looks at Abilify Maintena.