Last week the FDA issued a warning about Crestor — the cholesterol-lowering drug marketed by AstraZeneca. Among other things, FDA specifically suggested that lower doses of Crestor should be prescribed for Asian-Americans.

“In a pharmacokinetic study involving a diverse population of Asians residing in the United States, rosuvastatin drug levels were found to be elevated approximately 2-fold compared with a Caucasian control group. As a result of these findings, the “Dosage and Administration” section of the label now states that the 5 mg dose of Crestor should be considered as the start dose for Asian patients and any increase in dose should take into consideration the increased drug exposure in this patient population.” (See “FDA Public Health Advisory on Crestor (rosuvastatin)“).

This is an interesting sidebar to the Crestor story.

You’ve Heard of Ethical Drugs, But What About Ethnic Drugs?

The Crestor Asian sidebar issue will no doubt add fuel to the debate about racial differences and “racially based drugs and treatments.”

An article in the March 3, 2005 issue of Christian Science Monitor explores the “place for race” in medicine:

“Ever since the fall of the Nazis, the world has tried to keep the biology of racial disparity under wraps. It has been acceptable to link racial differences to social and cultural factors. One race might underperform another because of upbringing or poverty. But suggesting biology as the cause for those differences – like ‘The Bell Curve’ did a decade ago when it looked at academic achievement – was strictly taboo.

“Now, a new and unexpected force – medicine – is pulling back the covers. By taking a close look at minute differences in people’s genetic codes, researchers and drug companies are beginning to create racially based drugs and treatments.

“Given the prospect of targeting treatment, some scientists argue that the subject at least ought not to be taboo. Even if race eventually proves to be a crude and insufficient means of understanding genetic differences, it can play an important interim role, they say.”

(See “A place for race in medicine?“).

Whether or not race is a useful measure of genetic differences, pharmaceutical companies should not ignore the biological consequences of genetics in the development, testing and marketing of new drugs.

Traditionally the industry has focused on “blockbusters” and mass marketing in which one size fits all. Crestor is an example of perhaps the general rule — mostly ignored until now — that one size does NOT fit all. Not only does the same drug work differently in different people, but variations of a drug may be developed that are “targeted” or tailored to specific types of people based upon their genetic differences.

There has been much lip service paid to “targeted therapies” over the years (see, for example, “The New Branding Model: From Blockbusters to Targeted Therapies“), but very few drugs have been consciously developed to exploit genetic differences.

BiDil, which is expected to be approved for the treatment of congestive heart failure, has been cited as an “ethnic drug” in the Christian Science Monitor article. An initial trial revealed “much data comparing the Caucasian and African-American responses.” (see the presentation of the BiDil NDA before the EIGHTIETH MEETING OF THE CARDIOVASCULAR AND RENAL DRUGS ADVISORY COMMITTEE).

It turns out the BiDil wasn’t especially effective in Caucasians, but was very successful in increasing survival rates among African-Americans suffering from congestive heart failure (see “First Heart Failure Study in African Americans Shows 43 Percent Improvement in Survival“). African American patients with heart failure experienced a 43 percent improvement in survival after taking BiDil in this study. The results were so stunning that the trial was halted so that all participants could continue the therapy. Results of this drug trial will be presented at the 6th Annual Multicultural Pharmaceutical Marketing, Media, & Public Relations.

The Japanese have long contended that approval of drugs for use in Japan requires specific trials with Japanese participants because, they claimed, the Japanese physiology was different. My impression was that this attitude was always regarded as prejudiced and unscientific by Western drug companies.

It is interesting to note that the Japanese Ministry of Health, Labour and Welfare (MHLW) approved CRESTOR in Japan in December, 2004, at a dose range of 2.5-20 mg. According to an AstraZeneca Press Release, “The Council’s recommendation is contingent on final agreement of a post-marketing surveillance program. The recommended starting dose of 2.5 mg is in line with normal clinical practice in Japan where, compared to the western world, lower dose ranges of drugs, including statins, are made available.”

Multicultural Marketing
If drugs are tailored to specific genetic profiles, how will they be marketed to the public? Depending upon the size of the targeted group, mass marketing techniques (e.g., DTC on network TV) might not be effective, or at least would be very wasteful. The only feasible method of segmenting the market is to use race and cultural differences to target specific groups of people whose genetic makeup fits the profile of the drug; i.e., multicultural marketing.

Once BiDil is approved, for example, the DTC ads undoubtedly will be specifically targeted to the African-American audience segment. Such audiences “self-segment” themselves by patronizing specific media channels, TV shows, publications, etc. The advertising dollars, I am sure, will be much welcomed by media that service this audience.

Multicultural marketing has always had a place in the pharmaceutical industry, which targets specific populations depending upon the drug’s indication (e.g., diabetes and African-Americans–African Americans are twice as likely to have diabetes as white Americans of similar age; see Diabetes in African Americans).

Genetic Marketing
In the future, with more drugs tailored to individual genetic differences that are not necessarily based upon race or ethnicity, there will be a need for marketing techniques that go beyond multicultural marketing; i.e., “Genetic Marketing.” Genetic Marketing would target specific individuals based upon their genetic profiles. That would be a whole other level of personalization!