Friday, July 03, 2009

Novo Hopes Victoza’s EU Clearance Bodes Well for US

As the European Commission today gave its final green light to Novo’s much-anticipated GLP-1 inhibitor liraglutide (Victoza) (no surprise, given the CHMP’s positive recommendation back in April), the company’s still bullish on the drug’s prospects in the US—anticipating not only approval but a none-too-severe risk-management plan as well.

“Our expectation is that the whole post-marketing system that we’ll agree and adhere to in the US will not be of a severity that will be commercially destructive to the product, not prohibitive for easy daily use in the doctor’s surgery,” Novo’s CMO Mads Thomsen told us (but enough, one assumes, to give practitioners comfort and get a leg in versus Byetta…).

Thomsen’s taking heart, perhaps, from the squeaky clean EU approval, which came with no usage restrictions and no contra-indications—despite an earlier split vote from an FDA advisory committee in April over whether Victoza should be approved in the US at all, due to increased cases of thyroid tumors seen among rodents.

The European authorities apparently liked the sound of Novo’s commitment to undertake a global, 9000-patient, five-year post-approval cardiovascular outcomes trial, including not just the classical MACE analyses of CV risk, but also various thyroid-related parameters, according to Thomsen. “The plan is to have the study protocol negotiated with the FDA as well [as the Europeans] by year-end,” he told The IN VIVO Blog—and to start recruiting a couple of months later.

So does that mean US approval’s likely before year-end? Not all analysts are that bullish, given the challenges of monitoring any potential thyroid risk in humans (though the worst-case scenario for some, a black-box warning, doesn't necessarily kill sales--just look at Actos). But as far as Thomsen’s concerned, yes, “we’re assuming that either we have US approval by then, or that we’re so far down the regulatory process that the CV study design will be part of the discussions,” he continues.

Novo’s in a hurry because liraglutide is already late (speed-to-market hasn’t always been Novo’s strength, as we reported in more detail here, although product quality has more often than not made up for this). Lilly/Amylin’s long-acting Byetta (taken once-weekly vs once-daily for liraglutide) is close on Novo’s heels, and these companies, unlike Novo, have an existing GLP-1 platform to build on.

Still, Novo’s going to do its damnedest to leverage its own insulin sales force to get liraglutide out as quickly as possible to a broad prescriber base, says Thomson. Not unusually, the UK and Germany, two of Europe’s largest markets where up-front pricing is free, will be the starting points. “We’ll make some minor adjustments to sales force size in Europe,” he says, “but we’re only talking an additional 100 or so.” Thomson says that a “sizable” part of the insulin sales force will be re-allocated to liraglutide, at least during the launch phase, as the company tries to capture what it hopes will be “positive perception of innovation” at Novo among diabetes drug prescribers.

It won’t just be the specialists, though: since liraglutide is easier to use than insulin (it doesn’t require blood sugar monitoring or dose titration), “we anticipate a broader prescription base [than insulin] and moving into the GP market within several months,” says Thomsen.

Liraglutide will be positioned as “the natural second-line therapy after metformin failure,” explains Thomsen, given its “superior clinical profile, effect on body weight and lack of hypoglycemia.” In this regard, Novo’s racing not just against Byetta and family, but against the (oral, and thus highly convenient, and cheaper) DPP-IV inhibitors, too—like Merck’s Januvia and, shortly, AstraZeneca’s saxagliptin (Onglyza), which last week received a positive EU opinion. Indeed, “the question is whether second-line therapy is liraglutide, or another oral therapy,” summarizes Thomson.

Novo’s leading position in the insulin market means it isn’t about to admit that liraglutide’s success will eat into its core franchise. But even if it does delay progression to insulin somewhat, Novo’s hoping the drug allows to it capture patients earlier on in the course of their disease. The idea is that pre-insulin diabetics become loyal Novo followers, “using our services and devices, and…that later on, when they go onto insulin, they’ll add [Novo’s basal insulin] Levemir”—and not Sanofi-Aventis’ competing Lantus—on top of liraglutide, explains Thomsen.

That argument might well be boosted by recent data—albeit still controversial—linking Lantus to an increased cancer risk, a link Novo is trying hard to ring-fence as a Lantus-specific problem, not one that affects all basal insulins.

For the next chapter in Victoza’s US story, we’ll have to wait until August 6th and Novo’s half-year results. The company in early June met FDA to talk risk-management and to discuss Victoza’s victorious performance in a gutsy two-year head-to-head trial versus Byetta. FDA "didn’t have access to this material prior to the [April] advisory committee meeting,” clarifies Thomsen.

In this trial, liraglutide also showed itself as “drug squeaky clean with regard to calcitonin levels compared to comparator drugs…” hence “the [US] regulators will also believe, like us, that the benefit-risk profile of performing invasive procedures to monitor patients’ calcitonin levels is negative,” asserts Thomsen.

Are you listening, FDA?

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