Salix receives FDA approval for crofelemer to treat HIV-associated diarrhea

The following is being released by the American Botanical Council:

On New Year's Eve of 2012, the US Food and Drug Administration (FDA) announced its approval of crofelemer (Fulyzaq™, Salix Pharmaceuticals, Ltd., Raleigh, North Carolina) — marking the second time a botanical, and the first time an orally administered botanical, has received drug approval from the Administration. The first botanical drug to be approved in the United States was a topical green tea extract, Veregen®, in 2006. Both botanical drugs meet all US pharmaceutical requirements and can be dispensed only by prescription. 

Crofelemer is the first drug to be approved in the United States to treat HIV-associated diarrhea.It is derived from the latex of the South American sangre de drago tree (dragon's blood, Croton lechleri). A red, blood-resembling latex leaks from the tree when its bark is cut, and it is this substance that contains the novel polymolecular structure crofelemer, originally developed and standardized by Shaman Pharmaceuticals.

According to FDA's press release regarding the approval, "The safety and efficacy of Fulyzaq were established in a clinical trial of 374 HIV-positive patients on stable antiretroviral therapy [ART] with a history of diarrhea lasting one month or longer... Results showed that 17.6 percent of patients taking Fulyzaq experienced clinical response compared with 8 percent taking placebo. In some patients, a persistent anti-diarrheal effect was seen for 20 weeks."

The herbal medicine and pharmaceutical communities have been expressing satisfaction with FDA's decision, ushered out the door on the last day of the year — an action typical of FDA efforts to complete pending drug reviews before the end of each calendar year. Salix, which owns the license for crofelemer's development and submitted the product's New Drug Application (NDA) for review, called the approval a "significant step forward in addressing the unmet medical need of people with HIV/AIDS on ART who experience non-infectious diarrhea." According to a Salix press release, the company expects Fulyzaq to be available to patients in early 2013. A Bloomberg analysis estimates crofelemer will bring the company sales of $18 million in 2013 and $26 million in 2014. Napo Pharmaceuticals (San Francisco, California), the company that owns the intellectual property rights of the drug, will issue comments in the coming days (S. King, email, January 2, 2013). Glenmark Pharmaceuticals, Ltd., the India-based manufacturer and supplier of crofelemer for the US market, experienced an increase in market shares of 3.4 percent following the announcement.

The drug's approval marks an important event in the decades-long history of crofelemer. The original Investigational New Drug (IND) application was submitted by the now-defunct Shaman Pharmaceuticals (formerly in San Francisco, CA) in the early 1990s. In 2002, Shaman CEO Lisa Conte reorganized into Napo Pharmaceuticals, retaining Shaman's original intellectual property. In 2008, Salix obtained a license from Napo in order to continue to work toward crofelemer drug approval.

Salix filed the NDA for crofelemer in December 2011, which initiated the FDA review period. Due to the serious nature of the medical condition crofelemer treats, FDA assigned the NDA "priority review" status, which indicates that the Administration will aim to approve or reject the application in approximately six months. Although FDA accepted the NDA for filing in February 2012, it delayed its decision twice, including the most recent delay in September 2012, which added to Napo's concerns regarding the length of time it was taking Salix to move the product forward. In May 2011, Napo filed a legal complaint for breach of contract against Salix before the New York State Supreme Court, claiming that Salix was "unnecessarily stalling the advancement of this compound." Salix has maintained that it has proceeded with the NDA expeditiously. Although the lawsuit is still pending at this time, a ruling is yet to be determined.  

Updated and more extensive information on the crofelemer approval will be reported in the January issue of the American Botanical Council's monthly e-newsletter HerbalEGram, to be published online next week. Additional background on crofelemer is available in the following articles previously published by the American Botanical Council: