Complete Response Letter Review for December 2008

"Complete Response Letter" is a kind of funny term.  It implies finality when in fact, the outcome means that there is more to do.  During December, a number of companies got their marching orders from the FDA.  Here is a review:

• December 2 - Genta received a CRL for Genasense.  The CRL suggested the need for an additional clinical study.  The company has announced that it is appealing the decision.  Appeals are notoriously fruitless.  
• December 8 - Targenta received a CRL for its drug ortavancin for the treatment of complicated skin and skin structure infections.  The FDA said that the safety and efficacy of the compound had not been established and raised several safety issues.   
• December 11 - Pain Therapeutics received a CRL for REMOXY, an abuse-resistant controlled release form of oxycodone.  The press release talked about additional "non-clinical" data being needed, but it is quite possible the issue is a REMS program.   
• December 18 - UCB received a CRL for Neupro, an NDA seeking an indication for the treatment of signs and symptoms of advanced Parkinson's disease and as a treatment for the signs and symptoms of moderate to severe Restless Legs Syndrome (RLS).  The agency said that the company needed to first resolve an issue of crystal formulation in the patches.
• December 19 - Centocor received a CRL for ustekinumab for the treatment of adult patients with moderate to severe plaque psoriasis.  This is a biologic product.  The CRL requested a REMS, but did not request further clinical studies. 
• On December 22, AMAG Pharmaceuticals received a second CRL for ferumoxytol.  It is an intravenous iron replacement agent for the treatment of iron deficiency anemia and as a diagnostic agent.  The CRL appeared to ask for clarification of specific chemistry manufacturing controls and finalization of labeling. 
• On December 24, AstraZeneca received a CRL for Seroquel XR.  The NDA sought an indication for the treatment of Major Depressive Disorder in adult patients, but the company did not indicate the nature of the reasoning in the CRL for not approving the NDA. 
• On December 29, Ipsen received a CRL in response to its BLA seeking an indication for the treatment of cervical dystonia with Dysport.  The agency did not request new clinical studies but did ask for information regarding a REMS.   
• Also on December 29, Salix received a CRL for balsalazide tablets for the treatment of mild to moderate active ulcerative colitis in patients 18 and over.  FDA is asking for a new trial.

In sum, there were 9 CRLs issued in December with 2, quite possibly 3 and perhaps even 4 requiring further REMS work (pursuant to the podcast earlier this week on Eye on FDA aboutREMS).   Already in January, there have been at least two CRLs issued.

Comments

[Kerry Donahue]

A CR letter was a mechanism designed by FDA counsel in order to avoid transparency and accountability by the agency.

In form and function it otherwise operates no differently in the real world then a denial, but for some reason, to date, the fda gets everybody to see an apple where there is an orange.