Lilly's Prasugrel Widens the Gap

The gap just got wider.

No, we’re not talking about the income inequality gap, or the gender gap, or the generation gap. We’re talking about the approval gap for new drugs and biologics between Europe and the United States.

Some critics of the Food & Drug Administration argue that FDA is more conservative than its counterparts in Europe. (This is what we think of as the “too slow” contingent. FDA is also criticized from other stakeholders—like Sid Wolfe and Chuck Grassley—of being too fast.)

FDA disagrees with both sides. As Office of New Drugs director John Jenkins said at FDC-Windhover’s FDA/CMS Summit for BioPharma Executives, “We review each application on its own merits—not against some goal that we will approve 25 applications this year. Those that meet the standards under the statute get approved; those that don’t, don’t get approved.”

But with last Thursday’s news that prasugrel—Eli Lilly and Daiichi Sankyo’s beleaguered blood thinner candidate that is still sitting at FDA—received a positive recommendation from the European Union’s Committee for Medicinal Products for Human Use, the noise from the “too slow” contingent is likely to get louder.

In an effort to discredit those critics, Jenkins presented data at the FDA/CMS Summit from a preliminary analysis of new molecular entities reviewed by FDA and the European Medicines Agency between January 2006 and October 2008. What Jenkins found was that EMEA approved slightly more novel products than FDA, but that the agencies had a similar approval rate.

Jenkins then looked at new molecular entities that were reviewed by both the Food & Drug Administration. Of those 29 products, FDA approved two that the European Medicines Agency has not, and EMEA approved seven that FDA has not. (Once Lilly and Daiichi receive final approval from the European Commission—which should come in two or three months—prasugrel would make that eight.)

Jenkins argued that the numbers are too small to support any conclusions that FDA is more conservative than its counterparts in Europe—especially given that one of the EMEA-approved drugs (Sanofi-Aventis’ weight loss drug rimonabant) has already been withdrawn from the market.

Pointing to the list, Jenkins said: “Here’s where all the statements about the EMEA being faster are coming from.” But some investors still see the data as a troubling trend. The prasugrel approval in Europe is only likely to feed those beliefs. (You can read all about that debate in the latest issue of The RPM Report.)

So what's up with prasugrel at FDA?

As we’ve reported, FDA is looking at February 2009 for an advisory committee meeting. Assuming that happens, an answer isn’t likely much before March 2009—which would double prasugrel's review time to 12 months. The user fee deadline was initially set for March 2008, but on two occasions was pushed back three months—most recently to September. Since then, it has become just one of a number of missed deadlines at FDA.

Cleveland Clinic cardiologist Steve Nissen, who has accused FDA of being both too fast and too slow, thinks Lilly and Daiichi deserve an answer one way or the other. What do you think? Is FDA more conservative than EMEA? Or is the difference too small to draw any conclusions?

Photo courtesy of flickr user StevenBulman44.

More Information to Patients in Europe? Not Really

The industry dared to be optimistic, but was disappointed. Drug chiefs were hoping for more opportunities to communicate directly with patients in Europe, as part of much-needed change to marketing and selling models. (Read more on that in the forthcoming issue of IN VIVO).

Sadly, the European Commission's pharmaceutical legislation package, presented today to the Council of Ministers and European Parliament, "doesn't make a huge difference" to information provision in the UK, according to Richard Barker, Director General of the Association of the British Pharmaceutical Industry.

The proposals allow information which "does not go beyond the elements of the summary of product characteristics," plus "related information about non-interventional scientific studies," according to EC documents published today. And this information can be disseminated only via specialist publications and websites--no active distribution allowed. "It's a pull-model," summarized Barker--in other words, just about as far from DTC as it could possibly be.

Not that DTC was what the industry was after; it knows that doesn't work particularly well anyway (and some CEOs apparently hate it with a vengeance). But a little more freedom to communicate might have been nice. So would more clarity on whether information must be vetted pre- or post-dissemination: a summary memo released prior to the full documents states that "in general information will be subject to monitoring after it has been disseminated."

The full text, though--and what was picked up in this Reuters piece--says that "monitoring should be based on the control of information prior to its dissemination, unless the substance of the information has already been agreed by the competent authorities or if there is a different mechanism in place to ensure an equivalent level of adequate and effective monitoring." [our ital.]

Hmm. Assuming that last bit means that pre-vetting can be avoided (communication may prove highly burdensome if not) the proposals at least "don't take us backwards," adds Barker. In the UK, limited information is already available to patients via sites like medicines.org.uk. Like anything coming out of the EC, the package is a compromise between opposing positions. UK and Scandinavian attitudes to patient information contrast with that of France, for example, which remains highly sensitive to any sort of direct channel between manufacturer and patient.

Patient information is just one part of this story. Pharmacovigilance and counterfeit drugs feature too--though the branded sector missed out on a complete ban on the re-packaging of pharmaceuticals, which would have crippled parallel traders. (They rely on this to re-sell drugs bought in low-priced country A to higher-priced country B.) The finalized plan, unlike earlier drafts, states explicitly that "re-packaging remains possible"--a big nod in the direction of the parallel traders' lobby.

This set of legislation is tabled as a "renewed vision" for the European drug sector. But for Barker, it represents only a very small step, albeit in the right direction. "We need to go well beyond these measures to give a real boost to an industry's that's packing up and leaving Europe," he warns.

It's not enough to "launch reflections," as the EC is doing, on ways to improve market access and boost R&D. Aggressive action is needed if Europe isn't going to slide further behind, in particular given the rise of investment in developing markets. But aggressive action isn't what the EC does--or can--provide.