 | Quicker FDA Approvals Lately May be Due to Fewer Priority Applications
Two Winners in Targeted Therapies ‘Not Enough’ for Trend: Analyst
Quicker-than-expected FDA actions recently have the industry speculating about a possible speed-up by the agency.
Seattle Genetics’ antibody conjugate Adcetris won approval for two kinds of lymphoma, one week ahead of the scheduled deadline. Daiichi/Roche’s Zelboraf beat its PDUFA date by more than two months. Adventrx heard from the agency on Exelbine almost a month early. All of the actions took place in August.
Though each compound has its own characteristics, and reading the regulatory tea leaves is anything but simple, a big-picture view could explain the brisker actions, said Deloitte Recap analyst Elina Podvalny.
“The FDA review cycle time has decreased since 2009 which correlates with the FDA data that the number of priority review applications fell in 2009 and 2010 and the number of standard applications fell in 2010 as well,” Podvalny said, noting that the review cycle is affected by the total number of NDA and BLA submissions as well as the number of priority applications versus standard applications submitted.
Deloitte Recap data suggests that the number of priority review drugs approved in 2011 is rising in comparison to previous years and in proportion to the total number of drugs approved in 2011, Podvalny said.
According to the agency, after four years in a row (fiscal years 2005 through 2008) when the number of priority applications was never less than 30 and averaged 33, the number of priority applications decreased to 25 in 2009 and 19 in 2010. The number of standard applications increased each year from 2005 through 2009, averaging 103 submissions during the past four years (2006 through 2009). In 2010, though, standard applications dipped to 86.
Zelboraf, though, presents a special case, since advanced melanoma is an incurable disease with limited treatment options to which response is low, Podvalny noted. “Dacarbazine chemotherapy and interleukin-2 garner less than 20% objective response rates and show no evidence of improving median survival,” in clinical trials, according to Deloitte Recap data, Podvalny said. “Temozolomide, paclitaxel, and carboplatin show a similarly low response rate,” and combination chemo “gets slightly higher response rates, but still doesn’t boost overall survival” when tested in controlled studies.
The lack of good treatment options and strong efficacy results in the Phase III, Roche-sponsored BRIM3 trial may have sped the review (3.2 months) of Zelboraf and its approval, Podvalny said.
Zelboraf, a selective inhibitor of the activated BRAFV600 gene, is indicated specifically for unresectable or metastic melanoma with BRAFV600E mutation, as detected by the companion diagnostic, Roche’s cobas 4800 BRAF V600 Mutation Test (Roche Molecular Systems, Inc.), given marketing clearance at the same time as Zelboraf.
Two targeted therapies have won FDA approval so far this year. Two weeks after Zelboraf, the first, came Pfizer’s Xalkori (crizotinib), an oral, selective, ATP-competitive small molecule dual inhibitor of mesenchymal epithelial transition growth factor and anaplastic lymphoma kinase (ALK). Xalkori treats locally advanced or metastic non-small cell lung cancer that is ALK-positive as detected by the concurrently approved Vysis ALK Break-Apart FISH Probe Kit, from Abbott.
The two approvals are “not enough to signal a trend” favoring targeted therapies, Podvalny said. “We will need to observe what happens in the next few years.” |