Monday, May 05, 2008

Cimzia Launch: Nothing Simple About It

When UCB Pharma CEO Roch Doliveux delivered a status report to shareholders 10 days ago on the company's progress in transitioning to life after Zyrtec, one detail caught our eye: he crowed about UCB's ability to launch the TNF inhibitor Cimzia just 48 hours after approval.

In a follow-up press release, the company even identified the first patient to receive the drug!

You can understand UCB's excitment. The Cimzia approval for Crohn's disease was a much needed dose of good news, driving shares up 20% overnight, and surprising a lot of skeptics who wondered whether the drug would make it to the US market anytime soon. (And, yes, we certainly didn't expect it to be approved this soon.)

So a little cheerleading is understandable. But there are at least two reasons why UCB's rapid launch of Cimzia is worth further reflection.

First, it was not so long ago that product launches typically came weeks or even months after FDA approval. Before the beginning of the user fee era 15 years ago, the agency truly was a black box, where sponsors would have no way of knowing when (or if) FDA would be giving an answer. So valuable patent time would tick away while the sponsor digested the approval, scaled up manufacturing and prepared promotional materials for a launch.

Now, full-scale launches within hours of approval are routine. That is the value of the predictability and transparency of reviews in the user fee era. And that is a reminder of what is at stake if FDA fails to maintain that predictability during a period of intense strain. (Read more about how FDA is struggling to preserve predictability even as it plans to miss more user fee deadlines here.)

But there was nothing routine about the Cimzia review, and that is the second reason why Doliveux is right to applaud the work that went into the rapid launch. The Cimzia team faced an unprecedented challenge in getting the drug into the hands of patients: it is the first new molecular entity approved by FDA subject to the new Risk Evaluation & Mitigation Strategy and mandatory post-marketing commitment requirements of the FDA Amendments Act signed into law in September 2007.

The world has changed considerably since Cimzia was first submitted to FDA in early 2006. Its not just that UCB had to create a risk management plan for the drug; that has become a standard approach for many pharma companies for several years.

But it had to take that program and adapt it to the new REMS model, while the application was pending. Indeed, UCB did not know for certain earlier this year whether the REMS provisions would even apply to its product: that section of the law took effect in March, but FDA and industry have an extra six months to convert existing risk management plans into formal REMS. The law said nothing about pending applications; in the event, FDA decided to apply the new legal procedures to Cimzia.

So, not only did UCB have to design a risk management program--which it is calling CIMplicity--that would be robust enough to please FDA, it needed to ramp it up and roll it out on launch. That seems like enough reason to brag about getting the drug out in 48 hours. But doing all that while working through the uncertainy of the regulatory framework for the program is even more impressive. UCB had to stay abreast of FDA's thinking on whether and how the new law would apply to its product, and then make sure to involve everyone in the company who needed to sign off on a formal commitment to comply with the terms of the REMS.

Add to that the now mandatory post-marketing study requirements, another new challenge UCB had to navigate. According to FDA's approval letter for the product, UCB agreed to half-a-dozen post-marketing trials, signing off on them just two weeks before approval.

These are not the "we'll give it our best shot" pledges industry is used to in Phase IV, but legally binding agreements enforceable with fines. So when UCB agreed on April 8 that it would conduct a 10-year, 4,000-patient observational safety study, this was not a simple matter of giving FDA whatever it wants--this is a large undertaking that needs a great deal of organizational support.

So Doliveux is right to shower praise on the Cimizia launch team. The risk management plan may be called CIMplicity, but when it came to getting this product to patients in 48 hours, there is nothing simple about it.

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