FDA Evaluates Alli For Potential Serious Risk Of Kidney Stones

FDA adds kidney stones to the list of potential signals of a serious risk for alli based on AER information gathered between July and October 2011. GSK, which is confident in the safety and efficacy of alli when used correctly, placed the only OTC weight-loss drug on the auction block last April, but needs a buyer.

An FDA investigation into whether adverse event reports of kidney stones by alli userscouldsignal a serious risk might hinder GlaxoSmithKline Consumer Healthcare LP’s ability to divest the OTC weight-loss drug.

GSK “remains fully confident” in the safety and efficacy of alli (orlistat 60 mg) when it is used correctly, a spokeswoman said. The firm placed alli on the auction block last April, but has yet to find a buyer (Also see "GlaxoSmithKline's OTC Garage Sale Includes alli, FiberChoice" - Pink Sheet, 18 Apr, 2011.).

FDA added kidney stones to the list of potential signals of a serious risk for alli based on information gathered in the adverse event reporting system between July and October 2011, according to a quarterly update released Jan. 11.

The agency notes that it is evaluating whether alli’s current labeling, which warns users to consult their doctors before using if they have ever had kidney stones, adequately addresses other kidney-related adverse events.

FDA emphasizes that it has not concluded the drug poses a risk of kidney stones or identified a causal relationship between the drug and kidney stones. The agency says the addition of kidney stones as new safety information for alli does not mean patients should stop taking the medicine, but only that it “has identified a potential safety issue.”

GSK says in a statement that no clinical or preclinical data indicate orlistat has a direct impact on the kidneys, but acknowledges “some individuals may have a pre-existing condition in which they have increased levels of oxalate, one of the most common compounds of kidney stones, and may develop kidney crystals or stones while using alli,” which is why the label advises consumers who have a history of kidney stones to consult a physician before taking the weight-loss aid.

“GSK takes all reports seriously and continuously monitors the safety of orlistat and shares all relevant information with the FDA. The health and safety of the people who use our product is our number one priority,” the firm said.

The spokeswoman called the number of reports “extremely small” in the statistical context of the more than 12 million people worldwide who have used alli since it debuted over-the-counter in the U.S. in 2007.

Alli’s AER History

Alli has popped up on FDA’s adverse event radar screen before.

In June 2009, FDA announced an investigation into whether orlistat – the active ingredient in Roche’sprescription weight-loss drug Xenical (120 mg) in addition to alli – was connected to “rare reports” of hepatitis and liver injury. At the time, GSK argued alli is a “non-systemically” acting medicine with no obvious biological mechanism to explain how liver damage could occur. Nonetheless, the agency announced in May 2010 that it added a warning about rare reports of severe liver injury to the OTC Drug Facts label for alli (Also see "FDA Alerts Public To Ongoing Safety Review Of Orlistat In GSK, Roche Drugs" - Pink Sheet, 31 Aug, 2009.).

In February 2009, FDA noted in a quarterly adverse event reporting system update that it was evaluating whether adverse event reports of rectal bleeding signaled a potential serious risk with orlistat. In the most recent update released Jan. 11, the agency says it “decided that the current labeling for alli is adequate and that no further action is necessary at this time based on available information” related to rectal bleeding (Also see "FDA Evaluating Orlistat For Potential Serious Risks" - Pink Sheet, 9 Feb, 2009.).

However, the agency said it “is continuing to evaluate this issue to determine the need for any further regulatory action.”

The GSK spokeswoman said clinical and preclinical data do not indicate orlistat causes rectal bleeding.

FDA does not mention Xenical in the AER system update. An agency spokeswoman noted, “In general, safety reports may be more informative/detailed with the prescription product.”

Public Citizen Petitions For Ban

Adverse event reports related to liver, pancreas and kidney damage prompted Public Citizen in April 2011 to petition FDA to ban alli and Xenical (Also see "In Brief" - Pink Sheet, 9 May, 2011.). At the time of the petition, Public Citizen said FDA’s MedWatch reports identified 73 cases of kidney stones associated with Xenical and alli, 23 of which required hospitalization. A medical review by the advocacy group turned up at least three cases of acute kidney failure due to the formation of calcium salt crystals following the use of orlistat, the group said.

GSK backed orlistat’s safety in an Oct. 21 letter to FDA, in which the firm argued “repeated analysis of adverse event reports, together with pre-clinical and clinical trial data, do not indicate a causal relationship between orlistat and liver, kidney or pancreatic disorders.” It added its “ongoing safety risk evaluation supports the continuing use of orlistat and an overall positive benefit risk profile” (Also see "In Brief" - Pink Sheet, 31 Oct, 2011.).

An FDA spokeswoman confirmed that the petition still is under review.

Left Behind

Alli’s most recent potential safety issue could mar the weight-loss drug’s image at a time when GSK seeks a buyer for the brand.

GSK decided to divest alli in April after it “recognized that we lack sufficient critical mass in the weight loss category” and “other companies are better placed to maximize the potential alli offers,” the firm’s spokeswoman said. She emphasized GSK remains “proud of the many lives alli has helped change for the better since the launch,” which “remains one of the most successful product launches ever.”

Nonetheless, alli lingers on the sale rack despite quick turnaround of other brands GSK decided to divest at the same time.

Prestige Brands Holdings Inc. recently snapped up 17 OTC brands from GSK, but it did not buy the weight-loss drug, which has seen sales plummet since it switched Rx-to-OTC in the U.S. in 2007 and in Europe in 2009 (Also see "Prestige Acquires 17 Glaxo OTC Brands, Enters Analgesics Market" - Pink Sheet, 2 Jan, 2012.).

Alli sales fell 15% in the third quarter of fiscal 2011, GSK announced last October. While the firm did not attach a dollar figure to the brand’s sales, the decline is consistent with previous reports. Sales for the tablets in supermarkets, drugstores and mass merchandise outlets, excluding Walmart, were down 34.99% to $48.3 million in the 52 weeks ending Dec. 25 compared to the previous year, according to Chicago-based SymphonyIRI. Sales in calendar year 2010 were down 23.15% from 2009, which in turn were down 16.46% from fiscal 2008, according to the market information provider.

The fall contrasts sharply with alli’s strong start. Within its first two weeks on the market, alli sold $150 million, some of which represented stocked inventories (Also see "GSK Touts Alli As Tip Of OTC Strength, Reaffirms Consumer Commitment" - Pink Sheet, 30 Jul, 2007.). But sales began sliding the next year (Also see "Alli Sales Slender On Lower Retailer Demand, Flatten GSK Consumer Sales" - Pink Sheet, 28 Jul, 2008.).