Article reprinted from The RPM Report February 17, 2008
Office of New Drugs director John Jenkins debates the perception that FDA approves fewer products than its regulatory counterparts in Europe. But some investors see troubling trends in data presented by the agency at the FDA/CMS Summit. Find out why...
Article reprinted from The RPM Report February 17, 2008
Office of New Drugs director John Jenkins debates the perception that FDA approves fewer products than its regulatory counterparts in Europe. But some investors see troubling trends in data presented by the agency at the FDA/CMS Summit.
When it comes to the FDA approval process, Office of New Drugs director John Jenkins wants to make one thing very clear. All those external analyses that FDA is more conservative in its approval standards than its European regulatory counterpart are misguided and largely overblown.
During a keynote presentation at FDC-Windhover's FDA/CMS Summit for Biopharma Executives on December 4, Jenkins acknowledged recent criticism from analysts and sponsors about what they see as a slowdown in FDA reviews compared to the European Medicines Agency, or EMEA.
But he challenged the notion that FDA reviewers are slower and more conservative than their European colleagues. FDA and EMEA have "very different systems," Jenkins acknowledged, "but they often work in parallel."
"We review each application on its own merits—not against some goal that we will approve 25 applications this year. That's not the way we look at our work. We look at an application on its merits, and those that meet the standards under the statute get approved; those that don't, don't get approved. It's as simple as that."
Jenkins' Analysis Of Approval Trends
According to FDA's preliminary analysis of new molecular entity approvals between January 2006 and October 2008, while the EMEA approved slightly more products than FDA, the approval percentage was roughly equivalent between the two agencies.
For new molecular entities reaching their first regulatory action during that 34-month time period, Jenkins said, FDA approved 53 of 83 products (or 64 percent), while EMEA approved 62 of 92 (or 67 percent).
Since FDA and EMEA do not always receive the same applications, FDA then took its analysis a step further, and compared outcomes for products that were submitted and reviewed by both agencies.
Of those 29 products, eight were not approved by either agency, Jenkins said. EMEA approved seven products that FDA has not approved, and FDA approved two products that have not been approved by EMEA.
Wyeth's desvenlafaxine (Pristiq) for depression and UCB Group's certolizumab (Cimzia) for Crohn's disease are approved in the US, but are still pending in Europe. Neither cleared FDA easily; Pristiq was the subject of an "approvable" letter and Cimzia's review went past its user fee deadline.
A Bumpy US Road For European Approvals
Likewise, the seven products approved by EMEA had bumpy roads to approval in Europe, and have faced similar roadblocks in the US.
Sanofi-Aventis' weight loss drug rimonabant is probably the best example. EMEA approved Acomplia in June 2006, only to remove it from the market in October 2008 due to a risk of psychiatric adverse events.
In the US, Sanofi withdrew the rimonabant NDA (to be marketed as Zimulti) in June 2007 after an advisory committee found that the risk of suicidality was too great to recommend approval. (See "Sanofi-Aventis' Zimulti: Knowing When to Say When," The RPM Report, August 2007.)[2007500132]
Other examples, though, are less clear-cut. An FDA approval of Schering-Plough Corp.'s sugammadex (Bridion) for reversal of neuromuscular blockade after anesthesia could be years away, despite being well-received by EMEA.
Wall Street was caught off guard by Bridion's failure to reach the U.S. market, in part due to an encouraging FDA advisory committee recommendation and a positive opinion in Europe. Bernstein Research analyst Tim Anderson pointed to Bridion as an example of how FDA is becoming "increasingly unpredictable."
The pulmonary hypertension drug sitaxsentan (Thelin), which Pfizer Inc. acquired as part of the Encysive Pharmaceuticals Inc. purchase [200810018] in February 2008, has also had a rougher road in the US than in Europe, where it was approved in 2006.
There is some question now as to whether Thelin will ever reach the U.S. market. Pfizer is exiting cardiovascular drug development under a restructuring program announced in late September and is likely to abandon the NDA (See "Pfizer Backs Out of Cardiovascular R&D," The Pink Sheet, October 6, 2008.)
But to Jenkins, those seven products are too short a list to support the argument that FDA is more conservative than EMEA in reviewing novel drugs. Pointing to the list, Jenkins said: "Here's where all the statements about the EMEA being faster are coming from."
Investors Split On Conclusions From FDA Data
Investors on a subsequent panel during the FDA/CMS Summit were split on the conclusions that Jenkins drew from the data. T. Rowe Price VP Jay Markowitz agreed with Jenkins that the analysis did not seem to show an overly conservative FDA, as compared to EMEA.
"When I look at the seven drugs that were approved in Europe that weren't approved in the United States, there was nothing in my view that stood out like some great drug that the United States population is being poorly served by not having available," he said.
But Tony Butler, a managing director at Barclays Capital, found the trend line troubling. "We can talk about seven versus two not being a big number, but might it be a trend line?" he asked. "Whether or not that's the correct way to think about it ... that's a question that investors have."
Butler went so far as to question whether companies should consider leaving the U.S. market because of what has been perceived as a conservative FDA – a notion that Markowitz quickly dismissed.
"While I am happy to criticize things that I see as obvious, to me, I would not recommend that a sponsor develop drugs only in Europe now because the FDA is lagging behind the EMEA in terms of its willingness to approve new drugs," he said.
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