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GlaxoSmithKline’s Avandia (rosiglitazone) appears likely to get stricter labeling, per the recommendation of an FDA advisory panel, doctors said, adding that they are not necessarily signaling plans to immediately switch patients to newer classes of diabetes drugs.
That includes two products to recently come on the market, Amylin Pharmaceuticals’ Byetta (exanatide) and Merck’s Januvia (sitagliptin), chiefly because the medical community has yet to have a complete grasp on such newer agents, several physicians told this news service. Those drugs and others like them that remain in development hold promise, they said, but none has stood the test of time.
Dr Clifford Rosen of St Joseph Hospital in Maine, who chaired the FDA meeting, said in an interview that “sometimes the older drugs work just as well” at lowering diabetics’ blood sugar levels, which is why Avandia and other diabetes drugs are used in the first place. Older products include metformin and sulfonylureas, and while they also have side effects, he said physicians generally know what to expect with them.
However, Dr Richard Hellman, the president of the American Association of Clinical Endocrinologists and a professor of medicine at the University of Missouri/Kansas City School of Medicine, was more sanguine about sulfonylureas because of their cardiovascular side effects. But he said in an interview that he expects a bump in usage of metformin, which he termed “old reliable,” and also predicted more use of insulin, which he called “underutilized.”
Rosen added that while there is “big hope” for drugs that work like Byetta, a GLP-1 analog that is injected twice daily, he stressed that it remains “too early to tell” if those drugs or DPP 4 inhibitors like Januvia will provide perfect solutions for diabetics.
Such prudence on both new product classes was echoed by Hellman and Dr Irl Hirsch, a member of the American Diabetes Association and a professor of medicine at the University of Washington Medical Center, who cautioned that even though Januvia has exhibited a “very safe action profile to date,” safety issues could also creep up down the line.
Similarly, Dr Robert Vigersky, a member of the Endocrine Society and the director of the Diabetes Institute at the Walter Reed Health Care System, said uncertainties about the newer classes of drugs, particularly related to their known and potential side effects, may lead to safety problems down the road. Byetta, he said, causes nausea and vomiting, making it an intolerable option for some patients. Januvia, Vigersky said, seems to increase upper respiratory infections, which might signal changes in patients’ immune function.
Further, he said switching patients from one drug to another is not optimal, especially if their existing regimen is working as expected. Such decisions are likely to be made on a case-by-case basis, he predicted, adding that “everybody is going to have to make an individual judgment as to whether or not Avandia is the right drug at the time or whether someone who is on Avandia should be switched.”
As an alternate to moving patients to newer therapies, Vigersky said it may be more appropriate to switch them to a competing drug from the same thiazolidinedione (TZD) class as Avandia, Actos (pioglitazone). In fact, he said he “would feel safer” prescribing Actos over Avandia “at this point in time.” Hirsch also said he expects negativity surrounding Avandia to benefit Actos, from the Japanese pharmaceutical firm Takeda.
Hellman added similar thoughts, noting that Actos is “beginning to look more attractive,” putting Avandia at a competitive disadvantage, because “there is no evidence at this time that Actos has a similar cardiovascular risk.”
A panel of FDA advisors to the FDA yesterday said Avandia should remain on the market but also recommended that the agency add new warnings to its label to minimize its use in certain patients, particularly in those taking insulin or nitrates as well as those with heart failure. There already is a heart failure warning on Avandia’s label and that of Actos, but they suggested a black box to more prominently caution prescribers and patients.
Hellman said he expects a black box warning on Avandia’s cardiovascular risk to ultimately come from the FDA and speculated that “another shoe could drop” in the future, with much more data still to come, and prompt the product’s withdrawal from the market.
GSK, whose longtime blockbuster generated about USD 3.3bn in sales last year as its second-biggest seller, saw Avandia sales plunge 31% last quarter following the May publication of a meta-analysis by Dr Steven Nissen of the Cleveland Clinic that brought to light a higher rate of cardiovascular side effects in Avandia patients than previously believed.
Multiple DPP 4 inhibitors are in development to get to market behind Januvia, from New Jersey-based Merck. Takeda also has an investigational DPP 4 inhibitor in Phase III, as does UK-based GSK and New York-based Bristol-Myers Squibb. The FDA earlier this year rejected an application for another drug of that same class, Switzerland-based Novartis’ Galvus (vildagliptin), on worries about kidney impairment and a skin rash seen in monkey tests.
California-based Amylin’s Byetta, which is indicated for use in patients not achieving glucose levels with oral medications, is partnered with Indiana-based Eli Lilly.
Shares in GSK, whose market cap is about USD 142bn, climbed 3% from a one-year low ahead of the FDA meeting following the committee votes.
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