An active ingredient in Frontline is going off patent next year, leaving Merial's reign as producer of America's top-selling flea and tick control product vulnerable to copycat parasiticides and generics — competition that's already underway in European markets and Canada.

What does that mean for U.S. veterinarians and pet owners? It's likely that they soon will have access to new and possibly cheaper flea and tick control drugs that contain fipronil, including a new line of spray and spot-on pet parasiticides by Virbac called Effipro, slated to debut in America in 2011.

Fipronil is a broad spectrum insecticide that's one of Frontline's active ingredients. After Frontline is applied to the skin, fipronil is stored in the oil glands alongside hair follicles under the animal's skin and distributed continuously to the skin and hair as oils from the glands are released to coat the hair and skin through the hair follicles. In Frontline Plus, the slower acting and longer lasting agent, fipronil, is combined with (S)-methoprene (a growth regulator) to kill adult fleas within 12 hours of application, breaking the flea life cycle to prevent egg laying and further infestations.

Considering Frontline's popularity among pet owners, practitioners like Dr. Deborah Becker, a Veterinary Information Network (VIN) member who owns a clinic in suburban Philadelphia, are concerned that fipronil's move off patent will send consumers searching for a generic version of the drug. That's troublesome, Becker says, because she sells a significant amount of Frontline to her clients.

"I don't know exactly what Frontline sales represent to my bottom line, but it's sizable," she says. "Frontline is already sold online, where sometimes it's even cheaper than I can buy it. Now if there's a generic out there that's even more inexpensive, owners are going to get it. That's a concern since we are going to lose that business. These products help support the rest of the practice."  

By contrast, VIN member Dr. Carl Darby isn't moved by the news. The practitioner in Seneca Falls, N.Y., rarely sells Frontline, partly due to a trust issue he has with Merial. Like many of his colleagues, he believes that Merial officials look the other way as Frontline is distributed to Target, Costco and other retailers while, at the same time, the company promises to only sell the parasiticide through licensed veterinarians.

It's an accusation that Merial officials repeatedly deny, although the company does not sit alone in the hot seat. A veterinary-only sales policy has been adopted by other major pharmaceutical companies that sell pet parasiticides, even though such medications do not require a prescription. Like Frontline, Bayer's Advantage and K-9 Advantix, Pfizer's Revolution, and Novartis' Capstar flea treatments are still diverted to mass retailers despite promises to veterinarians to only sell through DVMs.

The fact that Frontline, like many of its competitors, can be found on store shelves breeds mistrust, Darby contends. "I'd have more respect for Merial if they just came out and admitted that they were selling it outside of veterinary practices," he says.

"I do feel like we don't always get told the truth by these companies," Becker adds.

One company poised to challenge Frontline's market share is Virbac, readying to soon launch its Effipro line of flea and tick control products to the U.S. market. Virbac Chairman and CEO Eric Marée has stated publicly that an "ambitious development program" has long been underway in anticipation of getting the green light to incorporate fipronil in flea and tick control medications.

Effipro products hit European markets last May. In a news interview, Marée says, "We expect to introduce the range (of Effipro products) on the American market where we already have a strong presence."

U.S. prices for Virbac's product have not been made public, but reports from pet owners overseas suggest that it is cheaper than Frontline, with some online pharmacies selling four tubes of Effipro for the same price as three tubes of Frontline.

Darby is less than excited about that. "There are 9 million different flea products on the market. Everyone is trying to get a piece of that pie," he says.

Pet owners already can buy generic fipronil for dogs and cats, both in spray and liquid forms, with Canadian online pharmacies selling products marketed as "generic Frontline," though the name-brand product is not licensed for use in the country. There are even Web sites where consumers can purchase just the active ingredient.

Dr. Joe Waldman, a VIN member who practices in Calgary, part of the Alberta province, says whether or not veterinarians and owners have access to fipronil matters little in areas of the country that are nearly devoid of fleas.
 
"We might see one or two dogs a year with fleas, and we keep a little Advantage (manufactured by Bayer) on hand to treat those cases," he says. "For those people who sell flea products, it's really a decent source of revenue. But very few people here keep their dogs and cats on flea and tick preventatives."

The opposite rings true in the United States, where it's estimated that Americans spend $1 billion a year to control their pets' fleas and ticks. Merial spokeswoman Natasha Jones says officials will not publicly talk about plans to maintain Frontline's dominance within America's pet-owning population. The company estimates that more than 1.5 billion doses of Frontline have been sold worldwide since its 1996 introduction. It's available in more than 150 countries.

"We've always had competitors," she says. "Certainly with fipronil going generic, this is a new wave that we've been preparing for, but we don't discuss our commercial strategy."

Fipronil was developed in the mid-1980s by scientists with Rhône-Poulenc S.A., which founded Merial in 1997 in a joint deal with Merck & Co. (See related chart, below).
 
Earlier this year, Sanofi-Aventis became the sole owner of Merial, in a deal that cost $4 billion. (Aventis was formed in 1999 when Rhône-Poulenc S.A. merged with Hoechst Marion Roussel.)

Sanofi-Aventis' latest performance report for 2009, filed on Oct. 30, reveals that Merial's third-quarter sales were flat at $636 million. For the first nine months of 2009, net sales of Frontline products were down 1.9 percent at $834 million.

During the same nine-month period, net sales of Merial's vaccines grew by 4.5 percent to $552 million. The growth, company officials say, was driven by companion-animal vaccines, with sales climbing by 9.1 percent.

Whether or not Merial will rely on vaccines to take the sting out of losing market share on its Frontline products remains to be seen. The company, a major producer of vaccines, has announced plans to open a reported $70-million production facility in China to create avian vaccines.

The Birth of Merial How one of America's biggest drug companies in animal health was created

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