Tuesday, August 12, 2008

The Case for Byetta LAR (Part 2)

Amylin and Lilly have high hopes for Byetta LAR, a once-weekly formulation of the incretin mimetic exenatide. Analysts are (as they tend to be) of two minds, with opinion ranging from those who think LAR may fairly quickly become the dominant brand in the entire diabetes class to those who wonder whether it will even make it to market.

We will leave the debate over the commercial prospects to others. But we do think LAR looks to have a winning profile from the regulatory perspective.

That, to put it mildly, is counterintuitive. We just wrote that it is harder than ever to get new type 2 diabetes drugs on the market. And we’ve said previously that it is harder than ever to get line extensions to market. (Remember Cordaptive?) That sure doesn’t sound like a good prognosis for LAR.

But this may be a case where two wrongs do in fact make a right.

How so? Well, first, this is a circumstance where it definitely helps to be developing a line extension rather than a new molecule. Here is how Amylin CEO Dan Bradbury described the situation during Amylin’s second quarter conference call. “The FDA panel meeting really focused on cardiovascular risks associated with new chemical entities,” he said. “That is one of the major differences here.”

Indeed, the panel vote does imply that marketed antidiabetic products just got a little more valuable. In fact, one implication of the latest advisory committee vote is that the decision by FDA to leave Avandia on the market is an even bigger victory for GlaxoSmithKline than it appeared. (An advisory committee voted overwhelmingly last year to allow continued marketed of the drug. FDA’s internal Drug Safety Oversight Board agreed, but by a single vote. And ultimately the decision came down to CDER Director Janet Woodcock, who opted to allow continued marketing.)

Now, Avandia (like other marketed products) will be expected to generate outcomes evidence—but at least it can continue to generate revenues in the meantime. And the odds of another TZD coming into the market any time soon just when down. So maybe, just maybe, GSK will actually see sales of the franchise rebound a bit in the years remaining before patent expiry.

But Byetta LAR is not a case of asking FDA to approve a new agent to lower blood sugar, but rather a case of asking FDA to approve an improved version of an already marketed drug. And, in fact, of a drug that has an attractive cardiovascular risk profile, given Byetta’s effects on weight and lipid levels.

That alone, though, may not be good enough in the current regulatory climate. But here’s the kicker: FDA can use the LAR approval to ensure it gets the outcomes data to support its decision to approve Byetta in the first place. The agency, of course, already asks for that data routinely—but as everyone saw with Avandia, those post-marketing commitments are seldom sufficient to generate definitive conclusions about the kinds of questions the committee now wants answered.

FDA, though, has a new tool it can use going forward: mandatory post-marketing study requirements, complete with the ability to levy fines against manufacturers who fail to deliver data by an agreed upon time. As we’ve said before, this changes everything about Phase IV.

The new authority is much easier for the agency to apply prospectively, to newly approved drugs (or at least new applications for expanded uses, new labeling, etc.). The agency can (and in the case of type 2 diabetes, we bet it eventually will) go back and add post-marketing requirements to already marketed products, but that is a process that will take some time.

So, Lilly and Amylin have a two-fold case for Byetta LAR. It is an improvement over an already marketed drug (since, the companies say, it provides better glucose-lowering control and increased convenience)—and it also gives FDA the opportunity to finalize mandatory outcomes studies for exenatide sooner than it otherwise could.

And, as an added bonus, it fits perfectly with the companies’ commercial positioning of the product. Lilly and Amylin are already planning a large cardiovascular outcomes study based on extensive trials suggesting beneficial effects on surrogate endpoints. So it shouldn’t be hard for them to commit to FDA to do such a study as a condition for approval.

All of which means Byetta LAR may turn out to be the right product for the current regulatory climate.

Of course, if the commercial product isn’t the same as the one used in clinical trials, all bets are off…

1 comment:

Anonymous said...

I think I pretty much understand what's being said here. Has anyone tried homeopathic HGH oral sprays?