Xenical Diabetes sNDA Withdrawn; FDA, Roche Disagree On Wording

Roche is contemplating how to pursue a type 2 diabetes indication for Xenical after withdrawing a supplemental NDA for the claim.

The company submitted an sNDA for Xenical (orlistat) on March 19, 2001, seeking a claim for use as an adjunct to other anti-diabetic therapies for the treatment of type 2 diabetes in overweight or obese patients. Roche hoped for an FDA approval by the end of 2001.

Roche withdrew the sNDA earlier this year when it became clear that it could not come to an agreement with FDA over the wording of the claim, the company said.

Roche expected that labeling negotiations could be difficult. At the time of the submission, the company noted that there would be discussion about whether the data support a formal indication or simply a reference to diabetic endpoints studied in conjunction with weight loss (¹ (Also see "Roche Agenda For 2001 Includes Kytril NDA For Post-Op Use, Pegasys Launch" - Pink Sheet, 19 Mar, 2001.), p. 18).

By last summer, Roche appeared confident that the claim would clear FDA before the end of the year. The company said it expected approval for use by obese diabetics to promote weight loss and help better control glucose levels ( ² (Also see "Roche Sees Pegasys Approval Delay Until 2002, But With Broader Indication" - Pink Sheet, 20 Aug, 2001.), p. 22).

The supplemental NDA included data showing that Xenical can lead to a three- to four-fold greater weight loss in diabetics compared to diet alone, Roche said. Orlistat was also associated with improved blood sugar and lipid levels, as well as a reduced need for anti-diabetic medicines.

Roche is still pursuing a diabetes indication. "As we move forward this year, we will be getting the characterization of Xenical and its role in patients with type 2 diabetes onto the label," CEO Franz Humer maintained during a Feb. 27 media briefing in Basel, Switzerland.

Roche believes a diabetes claim would encourage physicians to reconsider obesity as a medical condition, and help secure reimbursement for Xenical.

Reimbursement issues and physicians' "reluctance" to treat obese patients continue to hold back the brand, North America CEO George Abercrombie acknowledged during a press briefing in New York City Feb. 28.

In 2001, Xenical's U.S. sales declined 3% to $157 mil. (CHF 267 mil.), while worldwide sales were up 4% to $567 mil. (CHF 963 mil.). After a strong showing immediately after launch in 1999, Roche budgeted for Xenical to grow to $750 mil. in U.S. sales in 2000.

Roche now has much lower expectations. Humer characterized the 4% global growth rate as "quite a strong performance," noting that "we've driven that business with 30% less marketing investment." Over the next few years, Roche expects "steady, probably single-digit growth," he said.

Roche backed away from large-scale consumer advertising for Xenical and is focusing instead on patient retention. The company created a call center staffed by healthcare professionals and nutritionists to support the product ( ³ (Also see "Roche Xenical Patient Retention Program Is Key To Sales Growth" - Pink Sheet, 5 Mar, 2001.), p. 13).

With the program, Roche is "focusing more on people more likely to come into the patient pool, and, indeed, doctors that are more likely to participate with the patient," Humer said. As a result, 87.2% of patients remain on therapy after 12 weeks.

In explaining Xenical's slower-than-anticipated growth patterns, Humer said the drug cannot be seen as a "typical pharmaceutical," because "the patient has to have an active participation. You can't just take the tablets and ignore it. You have to actively participate in diet and exercise."

Roche is also in discussions with FDA over approval of the hepatitis C drug Pegasys (pegylated interferon alfa-2a). Roche received a "complete response" letter in April 2001, and later received another request for data on production scale-up.

The "requested data has been generated and will be submitted to FDA in the coming weeks," Roche said. The company expects approval in the fourth quarter for both monotherapy and ribavirin combination therapy.

With Schering's PEG-Intron brand currently in tight supply, Roche may have a window of opportunity to more easily establish Pegasys in the market ( ⁴ (Also see "Schering PEG-Intron/Rebetol Wait List Patients To Receive Drug By April" - Pink Sheet, 28 Jan, 2002.), p. 32).