Thursday, February 28, 2008

Novartis’ POC Bottleneck

Forget the R&D productivity crisis. Novartis’ translational medicine initiative—the bench-to-bedside concept whereby exploratory molecules are accelerated into human proof of concept trials—has been so successful that the Big Pharma now has a Phase II/III bottleneck.

So says Trevor Mundel, the architect of Novartis’ now much-expanded Exploratory Clinical Development group of ‘physician-scientists’, set up five years ago to provide a bridge between the Swiss giant’s research operations and the development group.

To clear that bottleneck, “we have to shift up a gear in the later development stages,” Mundel told IN VIVO Blog during the Economist Pharma 2020 conference this week (slowing down the early work isn’t an option).

And that, apparently, is why Mundel himself has moved from his previous role as Global Head of Exploratory Clinical Development into a downstream position, as Global Director, Immunology and Infectious Disease Business Franchise.

The therapeutic focus is no coincidence: these areas are particularly applicable to the translational medicine approach, since, with relatively well-defined pathways, they lend themselves to mechanistic and rational development—unlike, say, CNS, which remains somewhat black-box.

The move means Mundel gets involved in proving whether this translational medicine experiment will actually result in more approved drugs, rather than just a Phase II bottleneck. He gets to sort out issues such as how POC results are turned into concrete endpoints in regulatory studies, and to patch up any scientific disparities between early- and late-stage groups. Mundel claims proof of the pudding—in terms of a healthy late-stage pipeline and close-to or approvable assets—could come as soon as within the next three years.

Novartis needs the boost. It has been hit by a series of late-stage setbacks over the last 18 months, most prominently the US regulatory delay of DPP-4 inhibitor Galvus, the withdrawal of GI drug Zelnorm, and the non-approval in the US (and withdrawals elsewhere) of Cox-2 inhibitor Prexige. But Mundel sees the silver lining in these otherwise black clouds, too. “If anything these experiences have highlighted the importance of this R&D bridge and of doing better and deeper science,” he says. And as for the critics of Novartis’ R&D experiment (which, as we explain here, included the controversial appointment of ex-academic Mark Fishman and a massive investment on the East Coast), “there are fewer of them now asking whether this can work.”

The success or failure of Novartis translational medicine approach will be of interest to many besides the Swiss group and its shareholders. Fast-to-POC-focused groups are springing up all over the place, including at Lilly, where the slimline, low-cost Chorus group (read this) has even spawned an independent offshoot, Flexion. “They’re doing what we’re doing,” confirms Mundel. “The question is what happens after Chorus has been successful.”

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