Can a Biomarker Salvage Novartis' Joicela (AKA Prexige?)

In the "History of Troubled Drugs" playbook, lumiracoxib (Prexige, now called Joicela) is only a footnote, hardly a Vioxx or Avandia.

Prexige, however, may make a mark after all in pharma annals, far beyond its missed revenue opportunity or beneficial impact on patients. The drug, which is made by Novartis, is a selective COX-2 inhibitor, indicated for symptomatic relief of pain from osteoarthritis. COX-2s --as in the infamous Vioxx--are all but off the market in the US because of their cardiovascular side effects, but lumiracoxib binds to a different site on the COX-2 receptor, which may give it advantages that lift it from under the Vioxx shadow: minimal CV side effects, high selectivity, rapid cleansing from the blood and absorption into the inflamed joint.

The drug received European marketing authorization in November 2006 and launched in parts of Europe the following year. It has its own demons, however – rare but potentially fatal risk of liver failure at higher doses, and the FDA never approved it. In 2007, Novartis began under pressure from regulators to withdraw it from the market in the EU and elsewhere.

Now, as Joicela, lumiracoxib linked to a lab test may make a comeback. Novartis scientists have come up with a genetic marker, which they say can identify patients who are potentially at risk for lumiracoxib-associated hepatotoxicity. In essence, Novartis argues, patients who test negative for the marker aren't at high risk of liver side effects and can take the drug. Those who test positive for the marker should not get the drug.

It's an interesting case study in the murky, fragile world of companion diagnostics, which is starting to show up as more than a blip on pharma's radar. One indicator: Roughly a dozen or so diagnostic-drug companies deals with the aim of bringing a diagnostic and drug that are linked through to commercialization, were signed in 2009 --compared to seven in 2008. Novartis itself started a Novartis Molecular Diagnostics business unit--which is developing the diagnostic for Joicela and has 10 projects in the works --only little more than a year ago.

If Joicela makes it back on the market, pharma is likely to take note. For pharma, a biomarker strategy for rescuing flawed drugs holds tremendous appeal (think Exanta, Galvus, etc.), even if the ultimate market is nowhere near the original projections--especially if regulators accept data based on analysis of archived samples from previously completed studies. That's the approach Novartis has taken in Europe, where it submitted an application for marketing authorization in December 2009.

Novartis' next step in the US is less clear cut because the FDA has yet to propose a regulatory pathway for companion diagnostics --and the agency's paralysis has been a hurdle to say the least. Yet some good news happened on Feb. 25: Commissioner Margaret Hamburg for the first time publicly stated a timeframe: She expects the agency will propose companion diagnostics guidance this year.