Once again, the FDA’s actions have left me dumbfounded. It has imposed a potential company- destroying two-year approval delay on Indevus Pharmaceutical's (IDEV) lead product Nebido. Indevus' stock price has plunged 70% to an multi-year low of $1.19/share.
Nebido is a Bayer (BAYRY.PK) originated drug that is a long-acting preparation of testosterone that is used for replacement therapy for men with low levels of testosterone.
Low levels of testosterone increase with age and are a largely underreported and misdiagnosed condition. Low testosterone causes a constellation of symptoms including decreased sex drive or loss of libido, impotence, low muscle mass, increased fat mass, depression, fatigue, and a general decline in the general feel of well being.
In the United States, 38% of men at least 45 years old who visited a primary care doctor were found to have had hypogonadism or low testosterone levels. This represents a significant number of potential individuals who can benefit from hormonal replacement therapy.
Since there are 50 million men in America who are 45 or older, at a 38% prevalence rate of low testosterone, there are up to 17 million patients who could benefit from Nebido. Remarkably, only 1.3 million of those men are being treated.
While many patients rely on daily applications of testosterone cream, or biweekly intramuscular injections of testosterone, they suffer from a sawtooth pattern of testosterone concentrations leading to a fluctuation of symptom relief. Nebido avoids this with 12-weekly injections (once every 12 weeks), after physiological maintenance levels of serum testosterone are attained.
Nebido is the first and only long-acting testosterone preparation available in the U.S.
Why did the FDA significantly protract Nebido’s approval review date? It comes down to a few isolated cases of transient reversible shortness of breath and coughing following an injection.
In the U.S. clinical trials, which included a total of approximately 500 patients, there was a single instance of this phenomenon with the 750 mg (3ml) dosage of Nebido. The patient did not require medical intervention and the event resolved within 10 minutes. In Germany, there were some reports of the same phenomenon with the larger volume (4ml) 1000 mg dosage of Nebido.
Mind you, these were not results from German clinical trials. Instead, they are from post-marketing adverse reports that occurred (rarely) in Germany. The most serious side effects were even rarer: flushing, dizziness and fainting. There were no permanent injuries reported.
Most importantly, these adverse reactions were most likely not due to any pharmaceutical shortcomings inherent in the drug itself. Instead, they appear to be a result of improper injection of the drug itself resulting in venous absorption of the drug.
Once more, why would the FDA impose a two-year delay on a proven pharmaceutical product? Does the FDA know something the European Medicines Agency [EMEA] doesn’t?
Apparently not, since its the EMEA’s own data the FDA is relying on.
After all, Nebido has been in Europe since 2003, when it was originally approved in Finland and later in 2005, it was approved by a European mutual recognition procedure for the rest of Europe.
So, what is the problem? The problem is not with Nebido. The problem is with the FDA itself.
The FDA’s regulatory authority was perceived to be somewhat impotent following the Vioxx disclosures of repeated incidences of ignored signs of cardiovascular side effects. Likewise, the perception of FDA’s integrity was less than magic following the Provenge fiasco, where there were well-substantiated claims of conflicts of interests of FDA panelists involved in the delay of its approval. Assumedly, these shortcomings made the FDA act more aggressively- particularly following the recent humiliating congressional hearings.
But these FDA inadequacies did not give the FDA the right to sodomize Nebido’s chances of approval. Disgusting, isn’t it?