Released by FDA: 5/10/01.  Posted by FDA:  5/22/01

Sam Boddapati, PhD. 
Senior Director, Regulatory Affairs 
Supergen, Inc. 
Two Annabel Lane, Suite 220 
San Ramon, CA 94583

RE:    IND# [Confidential, deleted by FDA]
         Rubitecan 
         MACMIS ID# 9321

Dear Dr. Boddapati:

Through routine monitoring and surveillance, the Division of Drug Marketing, Advertising, and Communications (DDMAC) has become aware of promotional materials disseminated by Supergen, Inc. (Supergen) for the investigational drug rubitecan that misbrand rubitecan in violation of the Federal Food, Drug, and Cosmetic Act (Act) and its implementing regulations.   Specifically, Supergen is promoting the investigational drug, rubitecan, as safe or effective prior to approval on its website www.supergen.com (5/8101).

A sponsor shall not represent, in a promotional context, that an investigational drug is safe or effective for the purpose under investigation.   Supergen makes numerous claims regarding the safety and efficacy of rubitecan on its website.   These claims are based solely upon preliminary and inconclusive data since the clinical investigations of rubitecan are in the initial stages of investigation.   Therefore, the website is in violation of the Act and its implementing regulations because it promotes an investigational new drug as safe or effective for uses under investigation (e.g., prostate, breast, lung, ovarian, and pancreatic cancers).

Following are selected statements from the website that promote rubitecan as safe or effective:

“Miraculously, within just six weeks of Gordon’s taking Rubitecan - SuperGen’s “pill” for pancreatic cancer - the deadly tumor had shrunk to the size of “a golf ball,” Gordon remembers.  “Today,” he tells everyone who will listen, “all that’s left of that tumor is some scar tissue.  It’s gone.  Thank God.  Four months have turned into four years now.  And I feel great.   It’s really hard for me to believe / came so close to death.” (www.supergen.com)

“We at SuperGen, like Dr. Stehlin and others, believe that Rubitecan is a breakthrough drug because it has shown efficacy in many other tumors such as cancer of the breast, colon, and lung, in addition to the pancreas.   Rubitecan has also shown efficacy in blood cancers such as chronic myelomonocytic leukemia (CMM/myelodysplastic syndrome). "   (www.supergen.com)

"In early human studies Rubitecan also already has demonstrated anti-cancer activity against numerous tumors, including prostate, ovarian, lung, breast, colorectal and cervical, in addition to pancreatic cancer." (www.supergen.corn/product/2_3_1 .htm)

"In an ongoing Phase II trial, interim data has shown an improvement in patients’ quality of life, an increase in their survival rate and a reduction in tumor size (by both CT SCAN and serological markers).” (www.supergen.com/product/2_3_1.htm)

“Studies Show Supergen’s Rubitecan Has Anti-Tumor Activity Against Melanoma, Prostate and Lung Cancers” (www.supergen.com)  

“This wonderful medical institution was beginning human testing on an extraordinary cancer-fighting compound we now call Rubitecan.”  (www.supergen.com)

“Even beyond its broad potential range of activity, two other distinguishing features differentiate Rubitecan as a platform for leadership in solid tumors.   One is its side effect profile relative to other anti-cancer drugs.   In studies to date, none of the cardiac, pulmonary, hepatic or renal toxicities that limit the acute and/or chronic dosages of most chemotherapies have been observed and, in fact, some early studies suggest Rubitecan could be used to treat cancer on a chronic rather than acute basis. The primary side effects that have been observed are mild to moderate hermatological toxicities, low grade cystitis, and some gastrointestinal disorder - in all, a relatively benign profile.” (www.supergen.com/product/2_3_1.htm)

Furthermore, the presentation of rubitecan information on the “Products - Pipeline” webpage (www.supergen.com/product/2_2.htm) also promotes unapproved uses for rubitecan.   The chart shows uses for rubitecan that are investigational but use the word indication” as a “header” to describe investigational uses.   “Indication,” however, is a part of a specific heading (“Indication and Usage”) required in approved product labeling (PI).   This specific heading in the PI presents the approved indications for the named drug (approved by the Food and Drug Administration after review and approval of the applicant’s New Drug Application).   The use of “Indication” in the rubitecan pipeline chart is misleading because the listing of the terms “pancreatic,” “hematological,” “ovarian,” “colorectal “breast,” and “lung” under “Indication” suggests that these unapproved uses are, in fact, approved.

Finally, the “Products-Focus on Oncology” (www.supergen.com/product/2_3.htm) webpage on Supergen’s website does not distinguish between approved and investigational drugs.   This webpage presents investigational drugs and approved drugs on the same list.   Presenting investigational drugs in this manner suggests that the investigational drugs are approved when such a determination has not been made.

Supergen should immediately cease distribution and use of materials that promote rubitecan as safe or effective prior to approval.   This includes removal of similar claims and presentations on Supergen’s website.   Supergen should submit a written response to DDMAC on or before May 24, 2001, describing its intent and plans to comply with the above.   In its letter to DDMAC, Supergen should include the date on which this and other similarly violative materials were discontinued.

Supergen should direct its response to me by facsimile at (301) 594-6771 or by written communication at the Division of Drug Marketing, Advertising, and Communications, HFD-42, Rm. 17B-20, 5600 Fishers Lane, Rockville, MD 20857. In all future correspondence regarding this matter, please refer to MACMIS ID # 9321 in addition to the 1ND number. DDMAC reminds Supergen that only written communications are considered official.

Sincerely,

Joseph A. Grillo, Pharm.D. 
Regulatory Review Officer 
Division of Drug. Marketing, 
     Advertising, and Communications