Organon Contraceptive Maneuverings: NuvaRing, Implanon To Drive Growth

Organon expects a pre-approval inspection for the implantable contraceptive Implanon during the first half of 2003.

The company is projecting a 2004 launch for the product, Organon International President Hans Vemer told an analysts conference in London Nov. 6. The implant delivers etonogestrel for up to three years.

Organon had hoped to launch Implanon in the U.S. this year. However, "we had a hiccup in the production, going from the final Phase III into the production phase," Vemer said. "That has been resolved."

The first implantable contraceptive approved in the U.S., Wyeth's Norplant , is no longer available. The company cited production difficulties when it discontinued Norplant in July; the product has also been the subject of product liability litigation (¹ (Also see "Wyeth Discontinues Norplant: Contraception Removals Reimbursed To Dec. 31" - Pink Sheet, 29 Jul, 2002.), p. 36).

Organon says that Implanon is very popular with users in overseas markets. Implanon is "doing very well in the countries where we have introduced it, really in all layers of society, from government-funded family planning programs to high-level women in executive boardrooms," Vemer declared. Implanon is available in Europe, Latin America, Australia and New Zealand.

Vemer suggested that the delay in the launch of Implanon was "a little bit of a blessing in disguise," because it allowed the company to concentrate on the launch of the vaginal contraceptive NuvaRing (etonogestrel/ethinyl estradiol).

NuvaRing was approved by FDA in October 2001, but was not launched until July while Organon built up supplies and conducted a 15,000 patient test-marketing program (² (Also see "Organon NuvaRing Pre-Launch Distribution Program Will Enroll 30,000 Women" - Pink Sheet, 8 Oct, 2001.), p. 34).

According to Organon, the "Premier Program" found that 96% of NuvaRing users were satisfied with the product, and 78% are "extremely likely" to continue using it.

"That, by the way, confirms what I already know from the early clinical trials" of NuvaRing, Vemer said. NuvaRing is "the only product that even three years after the women ended the trial, they are still calling the company" to ask if it is available.

"The secret of NuvaRing is, you get women using it and then they will continue," Vemer said.

Organon began a direct-to-consumer print ad campaign in September. The company plans 87 insertions in 18 women's magazines through August. Organon has also set up a website (³ http://www.nuvaring.com/) which allow consumers to print coupons to receive the first month of therapy free of charge.

Organon has another innovative contraceptive product in late development. A "male pill" is in Phase II; the company announced Nov. 21 that it will work with Schering AG on the project. Any commercial launch is still at least five years away, Organon said.

Vemer did not discuss the product at length, saying only that "we continue to explore even more possibilities of maybe male hormone contraception."

Organon is counting on NuvaRing and Implanon to help the company essentially double the size of its contraceptive product line in the U.S. Organon's goal is for its contraceptive franchise to reach 1 bil. Euros in the U.S. by 2006.

The contraceptive line will be critical to Organon if it needs to bridge a gap in its product line between the potential onset of generic competition for the antidepressant Remeron (mirtazapine) and the pending antidepressant gepirone.

Several generic versions of Remeron are tentatively approved at FDA. Organon is in litigation seeking to block generic approvals based on a patent covering mirtazapine in combination with selective serotonin reuptake inhibitors (⁴ (Also see "USP Monograph Changes Could Be Strategy To Impede Generic Entry" - Pink Sheet, 25 Mar, 2002.), p. 5).

"I'm afraid I have no guidance as far as timing or the outcome" of the lawsuits, Vemer said.

Organon hopes to hold onto a portion of the mirtazapine franchise by switching patients to a quick-dissolving formulation (Remeron SolTabs). However, Vemer acknowledged that only about 35% of the market has switched to the newer formulation.

"That is good news and bad news," Vemer said. "Of course, we wanted more conversion. That is the bad news. The good news is that Remeron solid tablets are more expensive so we make more money on that."

Vemer maintained that Organon has had more success switching patients in the long-term care market, where about 65% of patients are on the newer formulation.

Organon could also benefit from a dispute between Mylan and Teva over which company is entitled to 180-day generic exclusivity for the product.

FDA awarded Teva the exclusivity for an ANDA filed shortly before Mylan's; Mylan, however, petitioned the agency in May to reconsider, claiming that Teva's ANDA was incomplete when it was filed because it referenced a non-existent drug master file. Both manufacturers have tentatively approved ANDAs.

The launch of generic versions of Remeron will have a significant impact on Organon's performance in the U.S. The product represents about 18% of Organon's overall revenues, and the company admits it will be difficult to grow sales and operating earnings in 2003 if generics are approved.

Organon had hoped to launch the antidepressant gepirone ahead of Remeron generics; however, the company received a "not approvable" letter from FDA in April.

The company is running additional studies of the drug, which it expects to complete during the third quarter of 2003. Organon believes FDA will take six months to review the new data, with a projected launch in 2004.

Organon will definitely not receive approval for its preferred trade name for the drug ( Ariza ). FDA rejected the name, and the company is applying for Variza as an alternative, Vemer said.

Organon is also facing a delay in entering the hormone replacement therapy market in the U.S. The company is developing a low dose formulation of its international estrogen therapy Livial (tibolone) for the U.S. under the trade name Xyvion . The company filed an NDA in 2000, but the product is back in Phase III.

Organon is now focusing on Xyvion for osteoporosis, with the goal of getting "an approval in the U.S. with better labeling than the products that are out there now," Vemer said.

The Women's Health Initiative study, which raised new questions about the safety of long-term HRT, has added another complication to the development of Xyvion, Vemer acknowledged.

It is not yet clear what FDA will require for approval of Xyvion in light of the WHI findings, Vemer noted, but the company's best guess is that FDA will "want to make absolutely sure that the product is safe as regards breast cancer...and they will probably ask for cardiovascular outcome data."

Organon is already evaluating both those issues in the ongoing trials, Vemer said. "If FDA does not change tremendously the requirements then we still think we can launch" in the 2004-05 timeframe, Vemer added.

The delays in the launches of gepirone and Xyvion have prompted Organon to cut back its primary care sales force in the U.S.

The company had built up to about 1,200 total sales personnel in the U.S. heading into 2002, but it has eliminated 180 of those positions. The cuts were "specifically in territories that are not so profitable in the U.S. where we couldn't make an inroad right now," Vemer said.

As part of the restructuring, Organon combined its primary care sales force with its women's health sales force, since "in the U.S., an OB/Gyn...is a primary care physician for women." The combined force numbers approximately 650 reps. Organon has also carved out a hospital sales force from within that group.

Organon is seeking in-licensing opportunities to help boost its primary care sales presence. "To be really effective, we need...more representatives in primary care," Vemer acknowledged, "and to be really efficient...we need and they need more products per representative."

"If there are spin-offs from other companies that they either cannot promote or for some reason or another are not interested in anymore, we'd like to look at those and would probably go for some of those." Vemer noted that the company's interest in in-licensing will increase if Remeron generics enter the market before gepirone is approved by FDA.

Another difficulty for Organon in the U.S. has been the slower-than-expected launch of the low molecular weight heparin Arixtra (fondaparinux), sold through a joint venture with Sanofi-Synthelabo. Organon has lodged a complaint with the Federal Trade Commission about what it believes to be anti-competitive contracting by Aventis in that market (⁵ , p. 13).