March 14, 2003
FDA Warns Public About
Misrepresentations in Marketing Claims About Drug to Treat Cancer
The Food and Drug Administration (FDA) is warning consumers and health care
practitioners about misrepresentations in a SuperGen, Inc. press release
dated November 15, 2002, in connection with a recently approved cancer drug,
Mitozytrex (mitomycin for injection).
The press release, entitled FDA approves SuperGen's New Drug Application to
Market Mitozytrex (MitoExtra) and disseminated by SuperGen, Inc.,
exaggerates the efficacy of Mitozytrex and fails to include the significant
risks associated with the use of the drug. Indeed, the press release does
not even mention acute adverse reactions that can result from administration
of Mitozytrex, which include fever, anorexia, nausea, and vomiting. The
press release also fails to disclose that Mitozytrex is associated with more
serious adverse events, such as myelosuppression and hemolytic uremic
A boxed warning included in the Mitozytrex package insert reads:
"Bone marrow suppression, notably thrombocytopenia and leukopenia, which may
contribute to overwhelming infections in an already compromised patient, is
the most common and severe of the toxic effects of mitomycin."
"Hemolytic Uremic Syndrome (HUS), a serious complication of chemotherapy,
consisting primarily of microangiopathic hemolytic anemia, thrombocytopenia,
and irreversible renal failure has been reported in mitomycin. The syndrome
may occur at any time during systemic therapy with mitomycin as a single
agent or in combination with other cytotoxic drugs, however, most cases
occur at cumulative doses greater than or equal to 60 mg of mitomycin. Blood
product transfusion may exacerbate the symptoms associated with this
The press release issued by SuperGen also makes unsupported claims that
Mitozytrex is a "supergeneric" from the company's Extra technology platform
and that the Extra technology is "designed to enhance generic drugs," that
is, create "improved generics, or supergenerics."
Mitozytrex is bioequivalent to the innovator mitomycin. It differs from the
innovator formulation only in that Mitozytrex contains the excipient
hydroxypropyl-beta-cyclodextrin (HPCD). No data submitted by the company
provided evidence that Mitozytrex is superior to existing marketed
formulations of mitomycin, and there is no evidence that the addition of
HPCD yields any clinical advantage over existing formulations of mitomycin.
Despite the absence of any evidence of such a benefit, SuperGen's release
states that "SuperGen's Extra technology is designed to 'shield' the drug
from the injection site, thus providing the patient protection from tissue
ulceration." This statement is unsupported. The adverse events associated
with Mitozytrex in the bioequivalence study conducted before approval were
consistent with those mentioned in the product labeling for the innovator
mitomycin. In addition, the repeat dose study provided no evidence that the
safety profile of Mitozytrex is different from the innovator mitomycin. In
fact, one patient in this study did experience tissue necrosis at the
SuperGen, Inc., claims in its press release that the company's Extra
technology could offer other important
advantages over existing generics, such as "increased solubility, stability
and shelf life." The instructions for
reconstitution of Mitozytrex and the innovator mitomycin, however, are
identical in terms of steps required and time necessary for dissolution. The
only difference is that Mitozytrex calls for a slightly smaller amount of
sterile water - an inconsequential difference. With regard to stability and
shelf life, storage conditions for unreconstituted Mitozytrex and the
innovator mitomycin are identical.
Finally, even though FDA rejected the name, "MitoExtra," as the proprietary
name for SuperGen's brand of mitomycin for injection, the company presents
the name "MitoExtra" as the drug's trade name in the press release. FDA
rejected this name because it suggests clinical benefits that have not been
substantiated by data. Notwithstanding this rejection, the name "MitoExtra"
is used "to market Mitozytrex (MitoExtra)." SuperGen also uses the name "MitoExtra"
interchangeably with "Mitozytrex" as the proprietary name. The FDA-approved
name for the drug, as it appears in the approved product labeling, is "Mitozytrex
(mitomycin for injection)."
FDA believes the characterizations of Mitozytrex (mitomycin for injection)
warrant clarification of the
record. The company's press release concerned an oncology drug, and FDA has
a practice of focusing enforcement resources on misleading information about
products intended for life-threatening conditions. Moreover, the company's
press release is particularly egregious in that it includes not only
misleading statements about the benefits of the company's drug compared to
other similar versions, but also statements that are demonstrably false.
Under the circumstances, FDA determined it was imperative to correct the
record, and to do so in a manner that would reached as many of the same
recipients of the original false and misleading messages.
The Federal Food, Drug and Cosmetic Act, gives FDA authority to disseminate
information to the public regarding drugs and other products within FDA's
jurisdiction to address imminent health dangers or gross deception. To
protect the public health, FDA is notifying the public that a particular
product has not been found by the agency to have benefits that its
SuperGen is based in Dublin, Calif.