Reading the April 21 warning letter from the FDA to Novartis is a bit like reading a primer on hownot to promote one's drug on the Internet. Where to begin? Well, Novartis was tagged by the FDA after its DDMAC division reviewed two web sites - gistalliance.com and cmlalliance.com - which were sponsored by the drugmaker, but are now out of commission.
The problem? The web sites don't mention the Gleevec cancer drug by name, but come close enough to ruffle the FDA. In effect, these disease awareness sites came off as so-called product branded sites. And so the agency writes these were "false and misleading because they promote the drug for an unapproved use, fail to disclose the risks associated with the use of Gleevec and make unsubstantiated dosing claims, (which) can put patients at higher risk of experiencing adverse events." Moreover, the materials placed on the site weren't submitted to the FDA at least 30 days prior to dissemination or submitted on the appropriate form as required by law.
Gleevec is approved to treat chronic myeloid leukemia (CML) and gastrointestinal stromal tumors (GIST), and the letter spells out the approved uses and dosaging, along with a host of violations, which the FDA describes as so "serious" that it demands "a comprehensive plan of action to disseminate truthful, nonmisleading, and complete corrective messages about the issues" cited in the warning letter. The FDA also warns Novartis about another site - bloodleveltesting.com. Here are some of the problems:
• The websites discuss the use of tyrosine kinase inhibitors (TKIs) for the first line treatment of GIST and CML, often in conjunction with the Novartis name. Gleevec is the only tyrosine kinase inhibitor (TKI) indicated for first-line treatment of chronic phase CML; the only TKI indicated for first line treatment of GIST; and the only TKI made by Novartis that is indicated for both GIST and CML. These product details are wellknown in the oncology community.
• The websites contain numerous references to the National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology, which recommend the use of Gleevec exclusively for the first-line treatment of CML and GIST.
• The websites are perceptually similar to the Novartis Gleevec product website, incorporating similar color schemes (including a distinct orange), design layouts and other presentation elements.
• The websites are clearly marked with the Novartis Oncology name and logo and/or the Novartis name and logo and discuss sponsorship by Novartis Pharmaceuticals Corporation.
• The healthcare professional-directed “Targeting BCR-ABL” webpage on the CML Alliance website provides a direct link to the Novartis Gleevec product website in reference to first-line therapy for CML, while the consumer-directed version of this page provides a link to the Novartis-sponsored “My CML Circle Program” website, which discusses Gleevec as a treatment for CML.
• The websites are registered to Novartis AG.
• The websites present data from imatinib clinical studies, and provide the corresponding literature references, which include the drug name in the listed publication titles. At least one of the publications4 recounts the pivotal clinical trial submitted to FDA in support of the approval of Gleevec in the treatment of adjuvant GIST.
7 Comments
As Ed notes, there are participants here who know much more about the particulars of the relevant shenanigan's than I do.
But what I find of more general interest is that DDMAC is now tightening the definition of what is a "reminder ad" when the relevant promo can only mean one particular drug (named or not).
If this is the enforded criterion, there are a lot of other busts that should be coming.
This is the first time I post here. This is big news and this is quite interesting how severe the warning letter to Novartis is. I am very interested in the issue the FDA is making about the potential for patients to be subjected to increased serious adverse events. There is not one TKI used to treat CML, or gist for that matter, that doesn't come without side effects that can be quite debilitating for the patient. CML is a deadly serious disease and although many CML patients are very grateful for the lifeline they have been handed with the advent of Gleevec and the support Novartis has given them, these patients are not out of the woods. A survey done by the largest CML patient support group showed that fully 85% of patients report serious side effects while on treatment with these drugs. These side effects prevent patients from interacting with their family, friends and in many cases interfere with their ability to make a living. On the other spectrum, there are some patients who report very little or no side effects, but they are clearly not the majority.
Can you imagine living many years paying for very expensive drugs that limit disease progression, do not cure the disease, but also subject the patient to years of grade 1 & 2 side effects. In some patients these are grade 3 & 4 and in some other patients there are adverse events that are life threatening. For many patients these grade 1 & 2 side effects make drug adherence a problem, then this give the disease a chance to become resistant to drug therapy. These patients then find themselves in a very precarious situation where their disease can progress to the more deadly phase. Thankfully there are second line therapies, but those therapies have side effects as well.
The lesson being learned here is that turning CML or any cancer into a chronic, drug dependent life long disease is a disservice to the very patient population being treated and to humanity in general.
We should be grateful that the FDA recognizes the seriousness of adverse events related to these drug treatments. Perhaps this will help raise awareness that research must continue towards a total drug free cure.
There are some very distinguished researchers out there trying to access funding to find ways to get rid of residual disease and potentially cure these patients. We need to align ourselves with that research. The NIH budget for cancer research is being increased to $1 Billion dollars - yet how many hundred billions do we spend every year on the war on terrorism. 40 - 50% of us will receive a diagnosis of cancer in our lifetime!!!
Where are our priorities? Are we really waging a war against cancer?
Thanks to Dr. Druker and Novartis CML patients are alive, but they are clearly not out of the woods.
Tyrosine Kinase Inhibitors are great drugs that specifically target the cancer cells, but that does not mean that they are not without serious side effects that can also be life threatening. We need to all pay attention to this.
So, the fact that Gleevec is the only approved first-line drug for CML or GIST means that novartis or anyone else for that matter shouldnt put out useful medical and scientific information? Why do we assume it necessarily biased? And as far as "side effects", we are a country of spoiled and ignorant folks, I fear. Of course all drugs have side effects; none are perfect. Thats why trials are done and the percentages and risks of potential side effects are reported in study results. If one doesnt want side effects then simply dont take the drug and continue to suffer the disease. The notion that drugmakers are uniformaly and purposefully "hiding" or "lying" about side effects is ludicrous. We cry when "not enough is done" to help those unfortunate to suffer any disease and when researchers and/or drugmakers respond with a validated teatment, we cry that its not perfect. How unrealistic and spoiled of us. The FDA weighs in late on Vioxx...a well known example of a rare case (i believe) where mistakes in reporting data may have been made, but here, where actual educational and helpful information is being provided, they are quick to act...and not entirely within reason. A lot of people will be deprived of very useful information because of this hasty and not-too-thoroughly-thought-out action. Mp
I agree with the FDA's concern over most of these issues, but 2 of them strike me as excessive:
* Referring to or citing clinical guidelines that support the use of your drug. Hello? If your product is innovative enough to be exclusively recommended by an independent group of medical experts, why should there be a problem? That's rewarding mediocrity and me-too drugs.
* Citing articles that mention your product's name in the title. Oh please. If the reference supports the claim, and the claim is germane and appropriate to an unbranded website, prohibiting the citation stifles education more than marketing.
Compared to the Topamax off-label case, the Vyvanse off-label imagery is pretty subtle and perhaps only people like me (and "Chad") would even think it was more than a coincidence. Images in direct-to-consumer (DTC) ads, however, are carefully chosen by pharma marketers and the FDA does pay close attention to them as part of the overall message.
I don’t work in cancer so maybe I’m way off based. But I wonder which drug the DDMAC pharmacist who wrote this would encourage his/her loved one to get if he/she contracted this disease?
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