FDA Approves Natesto, the First Nasal Gel Testosterone Replacement Therapy

June 25, 2014
Andrew Smith

This marks the first testosterone nasal gel for replacement therapy in adult males approved by the FDA for conditions associated with a deficiency or absence of endogenous testosterone.

Men who dislike any of the traditional options for testosterone replacement — options that range from implants to injections to gels — now have another: a nasal spray.

The US Food and Drug Administration approved Natesto Nasal Gel in May 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).”

Natesto’s maker, Trimel Pharmaceuticals, says the product combines the ease of traditional gels with a much lower risk that women or children will suffer secondary testosterone exposure.

Users squirt the gel up each nostril three times per day. Each squirt delivers 5.5 mg of testosterone, so the six total squirts (three in each nostril) provide users with 33 mg per day.

A 306-subject phase III trial evaluated Natesto over a 90-day period. Of the 78 patients assigned to self-administer the product, 73 were included in the Day-90 statistical evaluation of efficacy. 90% of those patients had testosterone levels within the normal range of 300 to 1050 ng/dL. Another 10% had below-normal testosterone levels, but none had levels that were above normal.

Adverse reactions experienced by more than 3% of the study group included an increase in prostate specific antigen, headache, rhinorrhea, epistaxis, nasal discomfort, nasopharyngitis, bronchitis, upper respiratory tract infection, sinusitis and nasal scab.

Trimel CEO Tom Rossi said the company would work to bring Natesto to market as quickly as possible and argued that the product would soon prove itself the safest and easiest way to take testosterone therapy.

The actual danger of secondary testosterone exposure is unclear, but reports of adverse events have been extremely rare. The FDA said in 2009 — nine years after it approved the first testosterone gel — that it had received only 20 reports of secondary testosterone exposure in all that time.

As for the ease of application, only time will tell how many men prefer sniffing testosterone at three separate times of day to spreading it across themselves once a day.

Some doctors have questioned whether Natesto will work properly for allergy-prone men who sneeze frequently or for sick men with runny noses. Others have questioned whether the novel application method could change the testosterone’s action inside the body.

A study published in 2009 showed that mice that received testosterone through the nose saw testosterone levels in their brains rise twice as high as mice who received the same amount of testosterone through intravenous injection.

Whether humans might experience similar results — and what such results might mean if they did occur in humans — remains unclear.

Natesto is one of at least half a dozen testosterone products to win FDA approval in recent years. Men who were once forced to choose between injections and gels now have the option of body patches, mouth patches, pills and others.

Hypogonadal men are not the only people that Trimel hopes to treat with its testosterone gel.

The company is also testing the product against female orgasmic disorder and made news recently by releasing top-line data from one phase II trial. Women who used the product during that 84-day study reported more orgasms with nasal testosterone than with placebo: 2.3 versus 1.7.