Propecia's Road to FDA Approval

The Bald Truth: The First Complete Guide To Preventing And Treating Hair Loss
by Spencer David Kobren

(Page 3 of 3)

On December 19, 1996, Merck & Co. filed with the FDA for approval the results of their thirdphase study of their hair-loss drug Propecia (I mg. finasteride).

Three months later, on March 23, 1997, they presented data from these phase-three (human trials) studies to the American Academy of Dermatology meeting in San Francisco.

The protocol for all of the studies within these human trials included the following:

• A total of 1,879 men participated.

• The men ranged in age from eighteen to forty-one, and they participated at a number of centers in the United States and worldwide.

• For twelve months each man daily received either a 1 mg. oral dose of Propecia or a placebo.

• The studies were double-blind, meaning that neither the patient nor the clinician administering the dose knew whether the patient was receiving Propecia or the placebo.

• Improvement was assessed by research investigators who examined each patient, by an expert panel of dermatologists who reviewed patient photos, and by the patients themselves, who filled out questionnaires at each visit.

• Each of the men participating had mild to moderate, but not complete, hair loss.

• Safety was evaluated through clinical and laboratory monitoring and analysis, and an analysis of adverse events.

The data presented at this March meeting was from studies of 1,553 men with predominant thinning of hair in the vertex area (top of the head). Overall improvement was seen as early as three months, with continued improvement over the course of the twelve-month trial period.

After twelve months, the results from the vertex studies were as follows:

• 86 percent of the men taking Propecia maintained or showed an increase in the amount of hair based on hair counts during the course of the studies, compared to 42 percent of the men receiving the placebo.

• 14 percent of the men taking Propecia lost hair (measuring any decrease in hair count from the baseline established at the start of the study), while 5 8 percent of the men in the placebo group continued to lose hair.

The difference between the men taking Propecia and the men taking the placebo is most dramatic in these two sets of results because they are based on actual hair counts, the most objective form of result assessment.

• Clinical investigators rated 65 percent of men treated with Propecia as having substantial increased hair growth, compared to 37 percent of the men taking the placebo.

• An expert panel of dermatologists evaluating patient photos rated 48 percent of patients treated with Propecia as having increased hair growth, while only 7 percent of patients taking the placebo were reported to show improvement.

• In the patient questionnaires, 68 percent of men taking Propecia reported that their hair loss had slowed, compared to 45 percent of those taking the placebo. Improvement was noted as early as the third month, when those percentages were 54 and 44 respectively.

"The clinical relevance of the increased hair growth measured by hair counts was substantiated by the significant improvements perceived by patients and through complementary measures such as the investigator and expert panel assessments," said Keith Kaufman, M.D., director of clinical research at Merck & Co., based in Rahway, New Jersey.

Three months later, on June 17, 1997, Merck presented data to the World Congress of Dermatology, meeting in Sydney, Australia, this time from their phase-three human trials studies of 326 men with frontal hair thinning.

As in the vertex studies, men with frontal thinning also benefited from Propecia, which prevented further hair loss and increased hair growth.

• Clinical investigators rated 52 percent of men treated with Propecia as having substantial hair growth, compared to 31 percent of men treated with the placebo.

• An expert panel of dermatologists evaluating patient photos rated 37 percent of patients treated with Propecia as having increased hair growth, while only 7 percent of patients taking the placebo were reported to show improvement.

• In the patient questionnaires, 53 percent of men taking Propecia reported an improvement in the appearance of their hair, while 30 percent of the men taking the placebo reported improvement. In addition, 65 percent of men taking Propecia, compared to 45 percent of men taking the placebo, reported that their hair loss had slowed.

Slightly lower effectiveness rates in the frontal studies are due to the fact that frontal hair is generally harder to regrow than hair at the vertex.

Investigators also reported a significant improvement for men treated with Propecia compared to those taking the placebo in hair density and pattern in three sections of the scalp-frontal, mid area, and vertex-throughout the studies.

Regarding the data reported in the frontal study, Merck's Keith Kaufman, M.D., said, "The frontal study is unique because hair-loss studies in men typically evaluate hair growth at the vertex. Frontal thinning is commonly seen in men, and it is what they may first notice when they look in the mirror."

Side Effects

Finasteride lowers the numbers in the PSA test (the prostate cancer screening test given as part of your general physical exam), and may therefore give you a false low-numbered status, thus masking levels of Prostate Specific Antigen that are actually higher. Tell your doctor if you are taking finasteride so that he will be able to properly interpret your PSA tests and order other screening tests that are not affected by the use of finasteride.

Regarding side effects, Merck's phase three studies of all the men participating show that "for the overwhelming majority of the men — 96 percent — these side effects were not reported," said Dr. Kaufman.

When side effects did occur, they "were reversible in men who discontinued therapy, and even resolved in many of these patients who preferred to continue treatment," Dr. Kaufman noted.

No birth defects were reported when several patients who were using finasteride impregnated someone.

The tolerability of Propecia was reinforced by the data from these human trials. The drug was very well tolerated, with most patients reporting no significant side effects. The overall safety profile for Propecia and the placebo was similar. Side effects were infrequent and occurred in a small number of men. The only side effects occurring in more than I percent of patients were the following:

• Decreased libido: 1.8 percent of men treated with Propecia vs. 1.3 percent on placebo.

• Erectile dysfunction: 1.3 percent of men treated with Propecia vs. 0.7 percent on placebo.

• Decreased volume of ejaculate: 0.8 percent of men treated with Propecia vs. 0.4 percent on placebo.

• Discontinuation of therapy due to adverse side effects occurred in 1.7 percent of 945 men on Propecia and 2.1 percent of 934 men on a placebo.

Propecia is for use by men only. Women "who are or may be pregnant must not use Propecia, since it may cause a specific birth defect in a male fetus," warned the company.

In their report of these FDA trial studies, Merck explained that "Propecia works by treating an underlying cause of male pattern hair loss by inhibiting the production of DHT, which is believed to be a major cause of hair loss. The enzyme Type II 5-alpha-reductase is involved in the production of DHT. Propecia inhibits the action of Type II 5-alpha-reductase, thereby decreasing DHT concentrations in treated men by approximately 60 percent."

Although male pattern baldness is genetically linked, its onset is triggered by the presence of DHT in the hair follicles of susceptible scalp areas, so "the ability to increase hair growth and prevent further hair loss by specifically lowering DHT with finasteride I mg. provides a potential new oral therapeutic option with an excellent riskbenefit ratio for the treatment of men with male pattern hair loss," Dr. Kaufman noted in Merck's report of their data. "This approach represents an important advance in our understanding of the science of hair loss. An important step in the development of Propecia was understanding the biology of male pattern hair loss and DHT's role in it. This knowledge has led to a new paradigm in treating men with this condition."

The positive results I have experienced while taking finasteride were confirmed by Merck's studies.

Merck submitted their application and study results to the FDA for clearance to market finasteride in I mg. pills under the brand name Propecia as the first oral treatment taken once a day for the prevention of further hair loss and for regrowth in the most common sites of hair thinning in men.

On December 22, 1997, the FDA approved Merck's application to market Propecia, and the prescription drug was shipped to pharmacies only weeks later, in January 1998.

With the introduction of Propecia and the many drugs that are sure to jump on the hair-loss treatment bandwagon in the coming years, treating male pattern baldness will be like treating any other chronic manageable disorder, such as hypertension or diabetes. Once the onset of the disorder makes itself apparent, the patient can go to the doctor and get a prescription for the problem.

Propecia can be used alone or in conjunction with herbs and/or a specific nutritional program that enhances hair retention and regrowth. Propecia is also a very effective adjunct treatment to hairreplacement surgery.

Baldness treatment pioneer O'Tar Norwood, M.D., who set the standard of pattern hair-loss classification with the Norwood Scale, has been following the ongoing hair-loss research and, like many other specialists, shares in the enthusiasm surrounding the breakthrough that finasteride represents with its ability to combat DHT's major role in male pattern baldness.

"The fact that it slows down hair loss," Dr. Norwood says, "is revolutionary. I especially encourage young patients who are too early for transplant surgery to use it, as well as those who can use it as an adjunct to hair-transplant surgery."

Those men with mild to moderate baldness will benefit. For those with more extensive baldness, the drug will reduce further hair loss and will encourage hair regrowth in those follicles that are still alive.

Propecia may be used alone or as an adjunct to other treatments, including nutritional, herbal, and surgical. Although Merck's studies are quite reassuring regarding the extremely low incidences of side effects, and the temporary nature of those side effects, caution should always be used when determining if any drug is right for you.

William R. Rassman, M.D., a leading hair specialist who with his colleague Robert M. Bernstein, M.D., perfected the follicular hair-transplant technique in the United States, believes that Propecia can be used alone or as an adjunct to other treatments, including hair-transplantation surgery, but he reminds us that as with many drugs, even those that have been used for a number of years, "all the long-term risks may not be known yet."

Now that the first treatment that actually acts upon the cause of male pattern baldness is on the market, men have the opportunity, if they so choose, to incorporate this drug into their hair-loss prevention and treatment.

Copyright © 1998 by Spencer David Kobren

About the Author

Spencer David Kobren is the country's most prominent and effective hair loss consumer/patient advocate, and the Founder and Director of The Bald Truth Foundation, the only organization dedicated to consumer advocacy, education and funding research regarding hair loss.