Trimel in pre-NDA meeting with FDA next month

By Len Zehr

Fresh from reporting positive Phase 3 results for its CompleoTRT intranasal gel for “Low T”, Trimel Pharmaceutics (TSX:TRL) plans to meet with the FDA in February to discuss its plans for filing a new drug application at the end of March.

“The pivotal results corroborated what we had anticipated in our statistical modeling and hit the FDA endpoints, so our product should be approvable,” Bruce Brydon, chairman, says in an interview with “We’ve seen our physician and patient market research provide excellent feedback as to the potential of the product, so overall, we’re thrilled,” he adds.

[Earlier this month, Mr. Brydon transitioned from chairman and CEO of Trimel, to the post of chairman. He was replaced as CEO by Trimel’s former president and COO, Tom Rossi, who continues as president and CEO.]

In mid-December, Trimel reported that after 90 days of product dosing, average serum testosterone levels for 306 patients involved in the study were within FDA efficacy guidance for a testosterone replacement therapy. Safety data were consistent with other testosterone therapies, and no drug-related serious adverse events were observed.

According to IMS Health, nearly 5.8 million testosterone prescriptions were written in the first ten months of 2012, reflecting growth of 34% over the same period in 2011. Mr. Brydon says the upswing in prescription growth rates reflects increased awareness of this medical condition by physicians and patients.

Sales in 2011 of marketed treatments for Low T were about $1.6-billion and have been projected to reach $5-billion by 2017, according to an independent research study. “I don’t see why we can’t get a significant share of that $5-billion market with the right partner,” Mr. Brydon figures.

He notes that Trimel has been speaking with potential marketing partners for a year or more. “Now with what we consider to be an approvable Phase 3 product, the partnering talks are heating up significantly,” he says, adding that the company expects to reach a deal during the FDA’s review of the NDA. He suggests the review process will likely take approximately 12 months, based on the last cycle of Low T products to reach the market.

“We have been working with a very large contract manufacturing organization in Germany, who would provide initial supplies of CompleoTRT to the marketplace. We also have been manufacturing clinical batches at a Mississauga [Ontario] site for well over a year, and it would be a secondary manufacturing facility going forward.”

Mr. Brydon explains that CompleoTRT is fully differentiated from potential competitors, noting that:

CompleoTRT’s significantly lower drug load achieves restoration of testosterone levels to the normal range employing much lower doses, both drug load and dose volume;
CompleoTRT’s nasal delivery system and proprietary formulation provide an uptake profile which closely mimics that of the secretion of endogenous testosterone in normal healthy males, thus helping avoid certain untoward effects associated with other marketed brands by eliminating the abnormal profile of constantly elevated circulating exogenous testosterone levels;
CompleoTRT’s circadian-like peak-and-trough profile indicates that it clears rapidly without significant drug build-up in the event a patient would require withdrawal of therapy, compared with wash out periods with competitors’ products that can take up to two weeks;
Application/dosing time for CompleoTRT takes a few seconds, compared with the 15-minute or longer application/dosing time of other products;
CompleoTRT’s multi-dose dispenser fits into a shirt pocket and travels easily for men on the go, compared with the bulky hand lotion-sized packaging of most competitors;
There is no messy complicated and time-consuming cleanup of the location where a patient applies his dose of testosterone.

“Most importantly, we do not expect the FDA to impose a black box warning on CompleoTRT,” Mr. Brydon says, pointing out that all other marketed brands carry a black box warning of testosterone transference to family members.

This form of transference, either primary or secondary, has resulted in serious consequences for children inadvertently exposed to testosterone, including the abnormal early onset of puberty in children of both sexes even at ages less than six years.

“Even if someone other than a patient were exposed to CompleoTRT, there isn’t any risk of unwanted absorption of the product, since our formulation does not include dermal penetration-enhancing chemicals,” he adds.

In October, Trimel reported results of an independent market research study of physicians. It found that physicians with previous experience with CompleoTRT would prescribe it to 36% of all of their Low T patients and 45% of their newly diagnosed Low T patients. Moreover, 77% of physicians responded that patients would not have an issue using an intranasal product. The benefits of CompleoTRT most often mentioned were safety, little or no risk of transference, ease of use and convenience.

Earlier this month, the company released positive results from a recently completed market research study that surveyed patients who participated in the CompleoTRT Phase 3 efficacy study. For those patients who had previous experience with other testosterone replacement therapies, 42% indicated that they felt better on CompleoTRT, compared with their previous experience, while 34% felt the same.

When asked if they would use CompleoTRT if it were approved and available by prescription, 70% of those who were previously treated with a testosterone replacement therapy said they would adopt CompleoTRT rather than return to their previous therapy. In addition, 84% of the patients participating in the survey were confident in applying CompleoTRT intranasally within two days of initiating therapy during the trial.

Mr. Brydon says Trimel expects to complete collecting additional nasal safety data in the current quarter on patients who will have been administered CompleoTRT for up to 360 days as part of the NDA submission. “This is local nasal tolerability safety data dealing with the root of administration and has nothing to do with testosterone,” he adds. “To date, we have seen nothing untoward and expect the final data to be extremely clean.”

Roth Capital Markets analyst Scott Henry initiated coverage of Trimel in October, with a “buy” rating and $3 price target, calling the company the “next big testosterone play.” The stock closed at $1.65 on Friday.

“In our opinion, selection of the correct marketing partner is a key variable to the success of CompleoTRT,” he said. “With a high level of promotional spending, we believe that patients will gravitate to a product that doesn’t have the risk of delivering unwanted testosterone to unsuspecting individuals. This marketing team could have the further advantage of marketing against [competitors’] black box label.”

Trimel’s next revenue driver is expected to be Tefina, an intranasal low-dose gel formulation of testosterone being developed to offer women experiencing Female Orgasmic Disorder (FOD), or anorgasmia, a ‘‘use as required’’ treatment option.

FOD is a persistent or recurrent delay in, or absence of, orgasm, following normal sexual excitement that causes marked personal distress or interpersonal difficulties. FOD affects one in five women worldwide. Currently, there are no approved treatments for FOD, which represents a significant unmet need for these women.

The company expects to finish, in the second half of 2013, a Phase 2 ambulatory study with Tefina, which is being conducted in the U.S., Canada and Australia with about 240 pre-menopausal women experiencing FOD. “There’s nothing we’ve seen that causes us to be other than bullish about the ability of the product to be safe and treat women effectively,” Mr. Brydon says.

As part of the study, patients will receive Tefina or placebo at home instead of in a hospital setting. The primary efficacy endpoint will be the increase in the occurrence of orgasm over the treatment period, compared against baseline levels.

If successful, Trimel may have to conduct two Phase 3 clinical trials, running concurrently, with as many as 700 patients and would likely take on a partner to conduct the pivotal trials.

When asked about the market potential of Tefina, Mr. Brydon says that the only model the company has seen that works is the Viagra model for erectile dysfunction in men, which resembles what he calls a “hockey stick” growth chart to reflect uptake and adoption by physicians and patients. He figures the market has the potential to generate $5-billion-a-year or more in revenue around maturity.

Another focus for Trimel in 2013 is advancing formulation work of its dry powder inhalation system in preparation for a Phase 2 asthma study with its TriVair bronchodilator in the second half of the year.

The company believes its technology platform will be the only available bronchodilator available in a dry powder inhaler format in the U.S. The unit-dose, dry power compound and inhaler has the potential to offer equal efficacy to currently marketed asthma medications, with reduced drug load, which should result in improved safety.

Mr. Brydon disclosed that Trimel also wants to expand its presence in public markets and is looking at a U.S. listing in 2013. “As a small organization, we have to weigh the extra costs and filing requirements associated with a U.S. listing.”

He says the company expects to start looking for other technology opportunities in the second half of this year. “For us, the indication is not relevant since we’re not a marketing company. It would be a question of the viability of the technology to produce an approvable drug and satisfy our criteria of financial requirements and market penetration. The excitement is reflected in the financial opportunity, which is different from other healthcare companies.”