Roche/GSK Boniva Launch Will Await Less Frequent Dose Approval

Roche and GlaxoSmithKline will hold off launching the osteoporosis agent Boniva (ibandronate) until approval of a less frequent dosing regimen.

A once-daily 2.5 mg tablet was approved by FDA May 16 "for the treatment and prevention of osteoporosis in postmenopausal women," labeling states.

However, "there are no immediate plans to launch the daily formulation in the U.S.," Roche said. "Instead, we will focus on clinical trials of investigational regimens for less frequent dosing."

"Our submission will be supplemented at the earliest possible opportunity, following the completion of ongoing Phase III clinical trials."

The decision to hold off launching Boniva reflects the availability of two once-weekly oral agents in the same category, Merck's Fosamax (alendronate) and Procter & Gamble/Aventis' Actonel (risedronate). Both companies have been successful in converting patients to the once-a-week regimens.

Roche is not disclosing the "less frequent" dosing schedules it is exploring. The company initially pursued a once-every-three-month I.V. infusion for ibandronate, which might have been a particularly attractive formulation for the Medicare market.

However, that development program was dropped in 2000 when a Phase III study failed to demonstrate efficacy of Boniva as an infusion every three months (¹ (Also see "Roche Likes Its Critical Mass But Could Amass More; $2 Bil. R&D Will Do" - Pink Sheet, 10 Apr, 2000.), p. 16). Roche and GSK entered into the licensing agreement for ibandronate in 2001.

Boniva labeling indicates another subtle dosing disadvantage for the drug that could potentially be addressed through further studies. As with Fosamax and Actonel, Boniva is supposed to be taken first thing in the morning before breakfast to minimize a food effect. Patients are directed to remain standing or sitting upright to reduce the risk of upper GI events.

However, Boniva labeling directs patients to wait at least 60 minutes before eating, while Fosamax and Actonel labeling recommends only 30 minutes.

GSK has a history of delaying launches to optimize the product profile, particularly for in-licensed drugs.

For example, the company held off launching Coreg (carvedilol) after it was approved for hypertension until it had approval for use in congestive heart failure. The product was developed by Boehringer Mannheim, which Roche acquired in 1997. Roche transferred exclusive U.S. rights to the drug to GSK in 2000 (² (Also see "Roche Kytril Acquisition From SmithKline Strengthens Hospital Focus In U.S." - Pink Sheet, 4 Sep, 2000.), p. 15).

GSK delayed the launch of Bayer's cholesterol agent Baycol (cerivastatin) while the companies pursued approval of a higher dose. The approach helped the product gain momentum commercially, but the drug was ultimately withdrawn after adverse reaction reports (³ (Also see "Baycol Withdrawal Gives Boost To Pravachol; Will Crestor NDA Be Affected?" - Pink Sheet, 13 Aug, 2001.), p. 4).

In deciding to delay the launch of Boniva, Roche and GSK have apparently concluded that the dosing disadvantages versus Fosamax and Actonel outweigh the interest in the bisphosphonate category as an alternative to estrogen replacement therapy for osteoporosis. The outcome of the Women's Health Initiative trial of Wyeth's Prempro has led to stronger recommendations to avoid long-term use of hormone therapies.

In addition to the dosing studies, Roche is continuing to develop Boniva for metastatic bone disease in breast cancer, Roche said. Phase III trials are ongoing; some data will be presented at the American Society of Clinical Oncology meeting in late May.

The Boniva NDA (21-455), received by FDA July 16, 2002, was originally submitted under the name "Bonviva." The name was modified and the change accepted by FDA during the review process, Roche said.

The drug was approved based on studies that demonstrated reductions of the incidence of new vertebral and non-vertebral fractures and improvement in bone mineral density in women with post-menopausal osteoporosis. Boniva was also shown to prevent bone loss in postmenopausal women without osteoporosis.

Ibandronate is the seventh new molecular entity approved by FDA this year, but only the second given a standard non-priority review.