What do you do after you lose interest in horses and your hockey team no longer wins? You try your luck in the biopharmaceutical business.
Eugene Melnyk the founder of Biovail is back again with a new company, Trimel Pharmaceuticals, stocked with Biovail alumni. He has also returned to a business strategy that was very successful at Biovail; take approved molecules and make them better using drug delivery technologies. This time though he has moved from oral sustained release products to intranasal and inhaled products. It’s the intranasal products that are most interesting.
Since leaving Biovail Melnyk has had his share of excitement, most of it unrelated to his Ottawa Senators NHL hockey team and horse farm in Florida. Earlier this year the Ontario Securities Commission banned him from senior roles at public companies in Canada for five years and penalized him CDN $565,000. He also settled with the US SEC paying a civil penalty of US $150,000 US on top addition to an earlier $1 million fine. These settlements were related to charges over financial figures in a 2003 press release, related in part to the infamous accident involving a shipment of Wellbutrin XL.
About those intranasal products. Trimel’s lead products are two hormone formulations of testosterone, an approved and well-accepted treatment for male hormone deficiency. What is most interesting is the delivery approach and the indications.
The lead Trimel product is Compleo, a Phase III stage intranasal gel formulation of testosterone targeted to androgen deficiency in men. This seems a tough market to crack. Although testosterone replacement treatment in the US is an attractive market with sales of more than $1 billion, it is very competitive. There are at least seven branded products already approved, with more in the development pipeline. These branded formulations of testosterone include gels, implants, metered solutions, transdermal patches and buccal tablets. And there are also the less commonly prescribed injectable formulations.
Trimel’s hook is that their product reduced interpatient transference of testosterone, an issue associated with the use of the gel formulations. This feature seems an unlikely benefit. Drug transference is a well-recognized problem that is easily managed with only a little bit of attention to personal hygiene. And Acrux’s marketed testosterone product Axiron addresses this issue head-on. Axiron’s delivery device, similar to a spray deodorant, limits hand contact, and the product is dosed underarm to prevent casual contact with others. The implants, patches and buccal formulations are even less likely to give rise to transference of drug.
Much more interesting is Trimel’s TBS-2, a lower dose intranasal gel formulation of testosterone targeted to the treatment of female anorgasmia. If Viagra popularized the expression erectile dysfunction, and the acronym ED, TSB-2 hopes to do the same for anorgasmia. In a recent press release Trimel defined anorgasmia as “a women’s inability to achieve or persistent difficulty in achieving orgasm even in conjunction with adequate sexual stimulation”. While anorgasmia applies to men and women, TBS-2 is targeted to the treatment of women.
Trimel is proposing to treat female anorgasmia by the intranasal administration of a low dose bioadhesive testosterone gel 30 minutes prior to physical stimulation. Trimel’s recently disclosed Phase II Vibro-Tactile Stimulation (VTS) clinical study “measured the effect of TBS-2 on the occurrence of orgasm, time to orgasm, the quality of orgasm, and placebo response rates for the anorgasmic patient population in order to assist in determining statistical power required in the AMB clinical study”. Apparently the results were sufficiently positive to permit an early termination of the study. The study presumably involves what its name suggests. Anorgasmic women were dosed with TSB-2 intranasally, provided a vibrator and asked to rate the outcome. This is a protocol not unlike those probably used to study ED drugs, although in the case of the latter there were harder endpoints.
TSB-2 represents one of the most ‘out-there’ therapeutic approaches I’ve seen. The suggestion that a small amount of testosterone, about one milligram, applied intranasally thirty minutes prior to sexual activity will enhance sexual satisfaction is incredible. It’s almost as though TSB-2 was acting as a pheromone. While androstadienone, a component of male sweat, has demonstrated some pheromone-like sexual activity, no pheromone has been shown to provide sexual attraction in a peer reviewed trial.
Anorgasmia is a complex condition with a very significant psychosocial component. Trimel says the US FDA recognizes anorgasmia as a medical indication. That’s a good start, but the hurdles to approval seem to be high given the likelihood of a high placebo response rate.
A September 26, 2011 article in Canadian Business suggests TSB-2 could be the female Viagra. It’s a little bit different of course. Viagra helps a man get into the game, while TSB-2 promises to help a woman win the game. I guess if it works, and is approved, TSB-2 can be a commercial success. An estimated 20% of women worldwide suffer from some degree of anorgasmia.
In terms of competition, BioSanté is in Phase III trials with their topically administered testosterone formulation, LibiGel. M et P Pharma AG has intranasal testosterone products that seem to be the licensed to Trimel, although this apparently has not yet been disclosed. Acrux’s Luramist, a spray formulation of testosterone, is in later stage development for female sexual dysfunction (FSD). Three other testosterone products for FSD from ProStrakan, Novavax and Proctor & Gamble, have been later stage clinical development failures.
In addition, Trimel has a nasal formulation of dopamine in preclinical development for Parkinson’s Disease and several inhalation products in earlier stage development, all of which seem to be branded generics. While Biovail was very successful with branded generics we’ll need to see if the market has the same appetite for this type of product. Risks are reduced, but so are the rewards.
Hockey, horses and hormones. Eugene Melnyk has to be hoping he has better luck with hormones than hockey and horses. Nowadays his Ottawa Senators can’t even beat the Toronto Maple Leafs. (Correction 2011-11-12, the Ottawa Senators came from behind to beat the Maple Leafs today.)