Galvus review delayed
As you’ll read in Therapeutics Daily and elsewhere, Novartis reported the delay of FDA’s review of Galvus, its answer to Merck’s recently approved Januvia, by three months. Novartis said it submitted additional clinical data, triggering the FDA to add time to its review-cycle clock.
What interests me about the story is the reasoning behind Novartis’ move. Apparently, in one or more monkey tox studies there was evidence of “skin lesions” that were of some concern. Presumably, Novartis was trying to head off a dreaded approvable decision or maybe a nasty label warning with the additional clinical-data submission. The nature of the skin lesions wasn’t elaborated by Novartis, although I read somewhere that blisters were involved.
It’s hard to deduce too much from this limited information, but what I can tell you is that monkey studies aren’t run to look for skin toxicity specifically, so if a skin finding was made in monkeys, it was made during the course of a general toxicology or safety pharmacology study (more likely the former). Also, Novartis wouldn’t have run a dermatotoxicity study (where the drug is applied to the skin) for an oral medicine like Galvus, so these skin lesions, whatever they are, were seen after oral administration.
Skin toxicity after oral drug administration is no rarity. All sorts of skin reactions can occur with systemically administered drugs. Usually such reactions are immune-mediated and most commonly are allergic reactions, including systemic contact dermatitis. What is quite unusual about this case, though, is that drug-related skin reactions occurring after systemic administration, immune-mediated or otherwise, are not usually not picked up during preclinical testing at all. They are usually first reported during clinical trials as human adverse reactions, sometimes not seen until after approval.
I couldn’t think of another example of a drug-related skin lesion following oral administration to monkeys, or any other non-human species, that was first seen during preclinical studies to compare with this case. If you know of one, please enlighten us.
For their part, Merck reportedly denied the existence of any skin tox findings with Januvia. Assuming that’s true, the Galvus monkey finding would appear to be specific to the drug and not an effect related to inhibition of DPP-IV per se. GSK, whose DPP-IV Redona (denagliptin) was recently put on hold in Phase 3 for undisclosed toxicity issues, didn’t comment on the Novartis news. Stay tuned for more from me on this story.
February 27th, 2007 at 4:59 pm
[...] When I reported on the initial Galvus approval delay in November, I promised a follow-up story. Yesterday, Novartis reported that FDA took the action of granting the Galvus NDA approvable status. Novartis had obviously expected this decision for a while, since label negotiations never occured, but the company chose to make the announcement after the decision was made official by FDA on the 23rd. [...]
May 16th, 2008 at 10:14 pm
[...] It’s looking like Merck got an incredibly lucky break here: Januvia sailed through FDA approvals and has come charging out of the gate with an “enormously successful start” (10% of new diabetic prescriptions). Meanwhile, its competitor from Novartis, Galvus, has been held up with the FDA for safety concerns. Hmmm… [...]