Endo Health Solution

FDA declines approval of testosterone drug for third time.

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In May, the US Food and Drug Administration (FDA) declined, for the third time, approval of Aveed, Endo Pharmaceuticals’ (Malvern, PA, USA) long-acting testosterone undecanoate injection, used for treatment of men with hypogonadism. Testosterone undecanoate is a long-acting depot formulation of testosterone in castor oil and benzyl benzoate. The FDA has concerns about reported side-effects of Aveed, which include anaphylaxis and pulmonary oil microembolism (POME). The FDA’s decision comes after an advisory committee to the FDA met in April to decide whether or not Aveed was a safe testosterone replacement therapy, in view of reports of severe post-injection reactions. The vote was split evenly, with nine members voting for approval and nine voting against.

Symptoms of male hypogonadism can include erectile dysfunction, infertility, a decrease in beard and body hair growth, and a decrease in muscle mass. In the USA, there are several approved testosterone replacement products, including orally administered formulations, patches, gels, oral tablets, and two already approved products for intramuscular injection. Aveed allows for a longer interval between treatments, with injections every 10 weeks compared with every 2—4 weeks for available injectable products.

In response to the most recent new drug application for Aveed, the FDA issued a complete response letter. According to an Endo Pharmaceuticals press release, although the letter did not request that the company do additional clinical studies, it did state that the company would need to submit an updated Risk Evaluation and Mitigation Strategy—a plan to manage known or potential serious risks associated with a drug or biological product. Specifically, the FDA requested that the company include a medication guide, which is a paper handout that comes with many prescription medicines to address issues specific to particular drugs. Such handouts contain FDA-approved information that can help patients avoid serious adverse events. The FDA also asked Endo Pharmaceuticals to produce an Elements to Assure Safe Use plan, which lists required medical interventions or other actions that health-care professionals need to take before prescribing or dispensing a drug to a patient.

“We are encouraged by the feedback received from the FDA in the complete response and appreciate the clarity around the path forward for Aveed”, said Ivan Gergel, executive vice president of research and development and chief scientific officer of Endo Health Solutions (of which Endo Pharmaceuticals is a subsidiary).

Aveed is the same formulation as Nebido (Bayer HealthCare Pharmaceuticals), a testosterone undecanoate approved for use in 94 countries, including those in the European Union. The fact that the same product is deemed safe for people in other countries but not in the USA has caused some physicians to question the FDA’s ruling.

“The side-effects the FDA reported are very uncommon, and this medication is available throughout the world except in the USA”, said Christina Wang, associate director of the University of California, Los Angeles Clinical and Translational Science Institute. “There have been millions of injections.”

Wang said physicians administering the product need to inject it slowly and make sure to not inject it into a vein, so that oil doesn’t escape into the blood. Wang has used this product in small clinical studies in which nurses have injected it under close supervision of doctors and “has never seen a severe allergic reaction”, she said.

John Morley, director of endocrinology and geriatrics at Saint Louis University School of Medicine (MO, USA), also was sceptical of the FDA’s reasons for denying approval for the product. He said many injectable drugs have side-effects. “I’m personally not convinced”, he said. “I follow the literature, and it seems like this product is a reasonable alternative for men who want to use it, as long as all of the side-effects are explained to them.”

The FDA denied the company’s new drug application for Aveed in 2008, citing safety concerns, and asked the company to provide additional information about the incidence of serious post injection POME and allergic reactions. The application was denied again in 2009, on the grounds of safety concerns because the Risk Evaluation and Mitigation Strategy that the company provided didn’t go far enough to ensure that the benefits of Aveed outweighed the risks.

Morley said there might be other underlying issues. The FDA might be reluctant to approve another testosterone product because such products are commonly being misused. People sometimes take the drug for non-medical reasons, such as attempting to increase sex drive and feel more energetic and young.

“The FDA has consistently ruled against many testosterone products”, said Morley. “In the back of the FDA’s mind they think every man is going to be given testosterone”, he said. “But we are talking about this being used in the hands of physicians who understand what they are doing. This is something the average physician could balance and make a reasonable decision about when and how this should be used in a small subset of people who it is appropriate for.”

The company will submit a response to the FDA by the end of the third quarter of this year.

Source: Lancet

 

FDA declines approval of testosterone drug for third time.

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In May, the US Food and Drug Administration (FDA) declined, for the third time, approval of Aveed, Endo Pharmaceuticals’ (Malvern, PA, USA) long-acting testosterone undecanoate injection, used for treatment of men with hypogonadism. Testosterone undecanoate is a long-acting depot formulation of testosterone in castor oil and benzyl benzoate. The FDA has concerns about reported side-effects of Aveed, which include anaphylaxis and pulmonary oil microembolism (POME). The FDA’s decision comes after an advisory committee to the FDA met in April to decide whether or not Aveed was a safe testosterone replacement therapy, in view of reports of severe post-injection reactions. The vote was split evenly, with nine members voting for approval and nine voting against.

Symptoms of male hypogonadism can include erectile dysfunction, infertility, a decrease in beard and body hair growth, and a decrease in muscle mass. In the USA, there are several approved testosterone replacement products, including orally administered formulations, patches, gels, oral tablets, and two already approved products for intramuscular injection. Aveed allows for a longer interval between treatments, with injections every 10 weeks compared with every 2—4 weeks for available injectable products.

In response to the most recent new drug application for Aveed, the FDA issued a complete response letter. According to an Endo Pharmaceuticals press release, although the letter did not request that the company do additional clinical studies, it did state that the company would need to submit an updated Risk Evaluation and Mitigation Strategy—a plan to manage known or potential serious risks associated with a drug or biological product. Specifically, the FDA requested that the company include a medication guide, which is a paper handout that comes with many prescription medicines to address issues specific to particular drugs. Such handouts contain FDA-approved information that can help patients avoid serious adverse events. The FDA also asked Endo Pharmaceuticals to produce an Elements to Assure Safe Use plan, which lists required medical interventions or other actions that health-care professionals need to take before prescribing or dispensing a drug to a patient.

“We are encouraged by the feedback received from the FDA in the complete response and appreciate the clarity around the path forward for Aveed”, said Ivan Gergel, executive vice president of research and development and chief scientific officer of Endo Health Solutions (of which Endo Pharmaceuticals is a subsidiary).

Aveed is the same formulation as Nebido (Bayer HealthCare Pharmaceuticals), a testosterone undecanoate approved for use in 94 countries, including those in the European Union. The fact that the same product is deemed safe for people in other countries but not in the USA has caused some physicians to question the FDA’s ruling.

“The side-effects the FDA reported are very uncommon, and this medication is available throughout the world except in the USA”, said Christina Wang, associate director of the University of California, Los Angeles Clinical and Translational Science Institute. “There have been millions of injections.”

Wang said physicians administering the product need to inject it slowly and make sure to not inject it into a vein, so that oil doesn’t escape into the blood. Wang has used this product in small clinical studies in which nurses have injected it under close supervision of doctors and “has never seen a severe allergic reaction”, she said.

John Morley, director of endocrinology and geriatrics at Saint Louis University School of Medicine (MO, USA), also was sceptical of the FDA’s reasons for denying approval for the product. He said many injectable drugs have side-effects. “I’m personally not convinced”, he said. “I follow the literature, and it seems like this product is a reasonable alternative for men who want to use it, as long as all of the side-effects are explained to them.”

The FDA denied the company’s new drug application for Aveed in 2008, citing safety concerns, and asked the company to provide additional information about the incidence of serious post injection POME and allergic reactions. The application was denied again in 2009, on the grounds of safety concerns because the Risk Evaluation and Mitigation Strategy that the company provided didn’t go far enough to ensure that the benefits of Aveed outweighed the risks.

Morley said there might be other underlying issues. The FDA might be reluctant to approve another testosterone product because such products are commonly being misused. People sometimes take the drug for non-medical reasons, such as attempting to increase sex drive and feel more energetic and young.

“The FDA has consistently ruled against many testosterone products”, said Morley. “In the back of the FDA’s mind they think every man is going to be given testosterone”, he said. “But we are talking about this being used in the hands of physicians who understand what they are doing. This is something the average physician could balance and make a reasonable decision about when and how this should be used in a small subset of people who it is appropriate for.”

Source: Lancet

 

FDA denies approval to Endo’s testosterone drug again

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The Food and Drug Administration has for the third time refused approval to Endo Health Solutions Inc’s injectable testosterone drug Aveed, pressing for a still better plan to manage the risks associated with the drug.

The denial comes as no surprise after an advisory panel to the FDA overwhelmingly agreed in April that Endo’s proposed plan for managing the risks associated with the drug was insufficient.

Testosterone, a hormone produced in the testicles, is responsible for maintaining muscle bulk, bone growth and sexual function. Lack of testosterone can lead to loss of libido, depression, decreased muscle mass and fatigue.

Aveed is made of testosterone and castor oil and the FDA has previously expressed concern of a risk that the oil could cause blockages in blood vessels in the lungs.

Lack of a suitable strategy to address these issues had led the FDA to refuse Aveed’s marketing application the last two times.

On Thursday, Endo said the agency wants it to include a medication guide and other some additional elements to its risk mitigation strategy to ensure the safe use of the drug and to avoid severe complications related to post-injection reactions, the drugmaker said on Thursday.

It, however, did not ask Endo to perform an additional clinical study.

Endo added that it plans to respond to the FDA by the end of the third quarter of this year.

Endo’s shares closed at $35.94 on Thursday on the Nasdaq and declined only marginally to $35.91 after market close.

 

Source: yahoo news