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Roche/GSK Boniva Launch Plan Includes Reminders For Once-Monthly Dose

Executive Summary

Roche and GlaxoSmithKline will support the launch of the osteoporosis therapy Boniva (ibandronate) with a program intended to help patients comply with the once-monthly oral dosing regimen

Roche and GlaxoSmithKline will support the launch of the osteoporosis therapy Boniva (ibandronate) with a program intended to help patients comply with the once-monthly oral dosing regimen.

The "MyBONIVA" patient support program will allow patients to sign up for reminders (by email, phone or regular mail) when it is time to take the medication. The support program will encourage patients to select one day a month as "Boniva Day" to help comply with the therapy.

Patients can access the program through a toll-free number (1-800-4BONIVA) or through a website, The support program is not yet live on the site.

FDA cleared the once-monthly dosage form of Boniva March 25. The product will be launched in April.

The support program is one unusual element of the marketing plan for the first once-monthly single tablet treatment ever approved by FDA.

Once-daily Boniva was approved in May 2003 for the treatment and prevention of osteoporosis in postmenopausal women. However, Roche and GSK decided to postpone launch until approval of a less frequent dosing regimen (1 (Also see "Roche/GSK Boniva Launch Will Await Less Frequent Dose Approval" - Pink Sheet, 26 May, 2003.), p. 20).

Boniva will compete with Merck's Fosamax and P&G/Sanofi-Aventis' Actonel in the bisphosphonate osteoporosis category.

Both Fosamax and Actonel are marketed in once-weekly dosage forms, which have all but replaced the once-daily treatments.

The once-monthly dosing schedule offers an obvious convenience advantage over the other brands, but brings with it some unusual challenges.

The instructions for patients get to the heart of a compliance challenge. "Choose one date of the month (your Boniva day) that you will remember and that best fits your schedule to take your Boniva 150-mg tablet," labeling says.

In the event that a dose is missed, "if your next scheduled 'Boniva day' is more than seven days away, take one Boniva 150-mg tablet in the morning following the day that you remember," the instructions for patients read.

"Do not take two 150 mg tablets within the same week," the instructions continue. "If your next scheduled Boniva day is only 1 to 7 days away, wait until your next scheduled Boniva day to take your tablet."

Boniva is also likely to be one of the most expensive medicines ever marketed on a per tablet basis. Roche and GSK have not announced a price, but say it will be "comparable" to other therapies.

Both Fosamax and Actonel sell for approximately $75 per month AWP in the once-weekly dosage forms.

At that price, Boniva would cost about three times as much per tablet as Novartis' oral chemotherapy agent Gleevec , and it would approach the price of Genentech's Tarceva on a per unit basis.

Roche and GSK plan to distribute Boniva in pharmacy shelf packs of three individually blister packaged doses. The packaging is intended to make it simple to dispense one-month or three-month supplies.

The high cost per tablet may also make sampling an unusual challenge for Boniva, since it may not be cost effective to fill a physician's cabinets with the product in the conventional fashion used for daily products.

The once-monthly formulation of Boniva is a 150 mg tablet, compared to a 2.5 mg tablet for the once-daily form. Labeling notes that ibandronate does not appear to be metabolized in the body; it binds to bone and is excreted in the urine.

Roche and GSK describe the film-coated tablet as "small" and "easy to swallow." However, like other bisphosphonates, it can cause esophageal irritation, and so labeling directs patients to take the tablet first thing in the morning (at least 60 minutes before eating) with a full glass of water. Patients are instructed not to lie down for at least one hour after taking the medicine.

The companies will launch Boniva in April with a sales force composed of reps from both companies. Detailing efforts will focus on primary care physicians, rheumatologists, endocrinologists and obstetrician/gynecologists.

Roche said the companies are planning a "substantial" direct-to-consumer advertising campaign for Boniva beginning later in the year.

The broadcast and print campaign will target postmenopausal females, encouraging them to talk to their doctors about new treatment options for osteoporosis, Roche said.

For Roche, the launch may be the first step in rebuilding a primary care sales presence. Roche's U.S. sales force is currently focused on specialty markets, and the co-promotion agreement with GSK for Boniva means the company can defer any decisions about investing in rebuilding a primary care infrastructure.

Roche may end up being one of the first companies that will attempt to tackle the primary care market without using a conventional pharma sales force. However, the company is not expecting new products for the general market until the end of the decade (2 (Also see "Roche Vision Of Rx Future Includes IT And China, But Not Large Sales Force" - Pink Sheet, 31 Jan, 2005.), p. 10).

For GSK, Boniva is a timely addition to the company's product line. An FDA seizure action over good manufacturing practices issues likely means the end of GSK's Paxil franchise - and could mean delays in some potentially important line extensions pending at FDA (3 (Also see "GSK Cidra Manufacturing FDA-483 Reports Cite Ariflo, 12 Other Products" - Pink Sheet, 21 Mar, 2005.), p. 17).

The once-monthly Boniva dosing regimen may not be the final step in formulation work in the bisphosphonate category. Roche is pursuing a once-quarterly infusion form of ibandronate; an NDA is pending with a user fee deadline in October.

Novartis expects to file an NDA for a once-yearly I.V. formulation of zoledronic acid for treatment of osteoporosis in 2007. The company will market zoledronic acid for osteoporosis under the trade name Aclasta (4 'The Pink Sheet' Jan. 24, 2005, In Brief).

Merck says it will focus on differentiating Fosamax based on efficacy, rather than dosing regimen.

The company recently released data from a 12-month head-to-head trial with Actonel, which found a statistically significant greater increase in bone mineral density in Fosamax patients (5 (Also see "Merck Fosamax Study Shows Benefit Vs. Actonel; Aventis/P&G Fault Endpoint" - Pink Sheet, 4 Oct, 2004.), p. 32).

Merck is waiting to conclude a second similarly designed study before submitting the data to FDA.

The approval of I.V. formulations would affect reimbursement: infused osteoporosis agents would be covered by the Medicare Part B program, while the oral therapies are not currently covered by Medicare, but will be paid for under Part D starting in 2006.

Approval for Boniva once-monthly was based on the Monthly Oral Ibandronate in Ladies (MOBILE) non-inferiority trial, which compared the monthly formulation to daily Boniva. The one-year trial included 1,602 postmenopausal women.

The study found once-monthly Boniva to be associated with a 4.85% mean increase from baseline in lumbar spine bone mineral density compared to a 3.86% increase for the daily formulation.

The 0.99% mean difference between the once-monthly and daily groups was statistically significant, labeling says.

"The 150 mg once-monthly group also had a consistently higher BMD increases at the other skeletal sites compared to the 2.5 mg daily group," labeling notes.

The most common adverse events with once-monthly Boniva observed in MOBILE were abdominal pain, hypertension, dyspepsia and arthralgia. Abdominal pain was more common in once-monthly Boniva patients when compared to daily patients (7.8% vs. 5.3%), while hypertension (6.3% vs. 7.3%) was less prevalent in once-monthly patients.

In conjunction with the new dosing regimen, Roche and GSK added a new bisphosphonate class warning on osteonecrosis and musculoskeletal pain (see 6 (Also see "Boniva Labeling Reflects Class Osteonecrosis, Musculoskeletal Pain Risk" - Pink Sheet, 4 Apr, 2005.)).

For prevention of postmenopausal osteoporosis, labeling includes data from a study of the daily formulation and notes that the once-monthly formulation is still being studied for prevention.

"The safety and efficacy of once monthly Boniva 150 mg in postmenopausal women without osteoporosis are currently being studied, but data are not yet available," labeling says. GSK said that it plans to initiate a definitive trial of osteoporosis prevention this summer.

Roche submitted the once-monthly Boniva NDA (21-455/S-001) March 25, 2004.

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