FDA OKs Natesto, First-Ever Nasal Testosterone Treatment

Miriam E. Tucker

May 29, 2014

The US Food and Drug Administration (FDA) has approved the first-ever nasal testosterone replacement therapy (Natesto Nasal Gel, Trimel Pharmaceuticals).

The product is approved for adult males with conditions associated with deficiency or absence of endogenous testosterone, including primary hypogonadism (congenital or acquired) or hypogonadotropic hypogonadism (congenital or acquired).

The product is self-administered into the nostrils via a metered-dose pump applicator. One pump actuation delivers 5.5 mg of testosterone, and the recommended dose is 11 mg (2 pump actuations, 1 in each nostril), 3 times daily (total 33 mg/day).

In a company statement, Jeffrey Rosen, MD, a family physician and medical director and founder of Clinical Research of South Florida, Miami, said that for men with symptoms of hypogonadism who seek to restore their testosterone levels, "Natesto will offer an alternative delivery system that is safer and more convenient than the other options currently available on the market."

Bradley D. Anawalt, MD, chief of medicine at the University of Washington Medical Center, Seattle, and chair of the Hormone Health Network for the Endocrine Society, gave the product a mixed review. "Intranasal testosterone gel offers yet another option for testosterone therapy that does not require intramuscular injection," he told Medscape Medical News.

And he noted that the nasal formulation offers a major advantage: "Because this gel is applied to the skin lining the inside of the nostril, there should little chance of transferring testosterone and causing higher-than-normal testosterone concentrations in women or children who come into close physical contact with the patient using the intranasal gel."

However, Dr. Anawalt pointed out that there are few published data on this type of testosterone therapy. Moreover, "For many men, the FDA-approved regimen of 3 times daily application of intranasal testosterone gel will be too Inconvenient."

And he adds, "It is also not clear how well intranasal testosterone gel will be tolerated by men with 'runny' noses due to viral infections or seasonal allergies."

Study Findings

Natesto was evaluated in a multicenter, open-label, phase 3 trial of 306 hypogonadal men at 39 US clinical research sites. The patients had a mean age of 54 years (range, 28 to 80) and were 89% white, 6% African American, and 5% Asian. Of 73 men included in the evaluation of efficacy at 90 days (which represents men started on a thrice-daily dose of the agent, rather than a twice-daily dose), 90% had average serum testosterone concentrations over 24 hours (Cavg) within the normal range (300–1050 ng/dL). The other 10% had Cavg below 300 ng/dL; none had Cavg above 1050 ng/dL.

Adverse reactions occurring in 3% or more of subjects in clinical trials were an increase in prostate-specific antigen, headache, rhinorrhea, epistaxis, nasal discomfort, nasopharyngitis, bronchitis, upper-respiratory-tract infection, sinusitis, and nasal scab.

Dr. Anawalt also pointed to a theoretic concern, that brain testosterone levels will be much higher with intranasal testosterone gel than with other testosterone treatments. A study published in 2009 using mice showed brain levels of testosterone that were about twice as high in mice who received intranasal testosterone gel than in mice receiving intravenous testosterone. "What this finding means and whether it applies to men is unknown," he told Medscape Medical News.

His advice for physicians regarding this product: "Proceed with caution."

Dr. Rosen reports that he is or has been an investigator for Trimel, Lipocine, Merck, Nektar, GlaxoSmithKline, Novartis, Novo Nordisk, Protein Sciences, Vivus, Essai, Pfizer, Boehringer Ingelheim, Isis, Takeda, Sanofi, Sanofi Pasteur, Genkyotec, Lilly, Trans Tech, Alcon, Amylin, Bristol-Myers Squibb, Dey, Febridex, Forest, Intarcia, Kowa, Lithera, GenProbe, Pronova, Roche, US Micron, Shionogi, and Toyoma and is a speaker for Vivus, Merck, and Sanofi Pasteur. Dr. Anawalt has disclosed no relevant financial disclosures with regard to any testosterone product.


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