Napo Pharmaceuticals, Inc. ("Napo") was informed today that the Food and
Drug Administration ("FDA") is continuing its review of the new drug
application ("NDA") seeking approval of crofelemer for the treatment of
chronic diarrhea in people living with HIV/AIDS on anti-retroviral
therapy. Salix Pharmaceuticals, Inc. ("Salix") never informed Napo that
Salix had filed the NDA for approval of crofelemer as a botanical drug.
According to the FDA website, "botanical drug products are complex
mixtures with a lack of a distinct active ingredient and substantial
prior human use as a complex mixture. Fermentation products and highly
purified or chemically modified botanical substances are not considered
botanical drug products." The FDA has never previously approved an
orally acting botanical drug.
Crofelemer is a natural product isolated and purified from a tree found
in the Amazon Basin, Croton lechleri. In contrast to the FDA
definition of a "botanical drug product" - which indicates a
"substantial prior human use as a complex mixture" - crofelemer has been
developed since 1992 as a highly purified and characterized "new
chemical entity" (or "NCE") under strict development and manufacturing
guidelines that included 20 years of FDA-approved human clinical trials.
(According to the FDA, "some 25% of all NCEs approved by the FDA between
1981 and 2006 were unaltered natural products [like crofelemer] or
derived from natural products." This highly purified chemical entity is
substantially different, safer, and more effective than the raw natural
sap of Croton lechleri - known locally as dragon's blood. In
substantial and documented communication with the FDA from 1991 through
2011, crofelemer was described and referred to by all parties -
including Salix - as a NCE drug, not a botanical drug.
In late 2010, Napo and Salix - with rights licensed from Napo to develop
and sell crofelemer - completed a Phase 3 clinical trial (know as the
"ADVENT trial") that exceeded endpoints for efficacy and demonstrated
the same safety/tolerance profile as the placebo. Salix stated in
November 2010, after announcing top-line results of this study, "We are
proceeding with efforts to submit a New Drug Application ("NDA") based
on the results of this trial. We have requested a pre-NDA meeting with
the FDA and believe that a meeting could be scheduled by mid-first
quarter of 2011. The ADVENT trial was conducted under a 'fast track'
status and has been part of a 'special protocol assessment' (SPA)