Healthy Skepticism Library item: 512

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Publication type: Journal Article

Monarin G-L.
Proceed with caution
Med Ad News 2005 Mar; 24:(3):
http://www.pharmalive.com/magazines/medad/view.cfm?articleID=1872

Abstract:

Safety concerns prompt FDA to be even more careful about switching drugs
from prescription to OTC status, but experts say the number of switches will grow.

Full text:

The U.S. Food and Drug Administration is favoring caution when it comes
to approving over-the-counter drug switches, but at the same time the
agency intends to increase the rate of OTC switches. Merck & Co.‘s
Mevacor was rejected by a joint FDA advisory committee Jan. 14 based on
patients’ inability to self-select for treatment and to comply with
long-term use and testing. The joint committee voted 20 to three against
the OTC marketing of Mevacor 20 milligrams, which was to be sold under
the proposed trade name of Mevacor Daily. Experts say the committee’s
move will probably set the standard for other statins to follow, such as
Bristol-Myers Squibb Co.‘s Pravachol. FDA already rejected OTC switch
proposals for these two drugs in 2000. Other companies that aim to
market their drugs over the counter include Roche, which received rights
to develop the weight-loss drug Xenical as an over-the-counter product,
and Barr Laboratories, which submitted a proposal for its emergency
contraceptive Plan B. A spotlight on safety will likely slow the OTC
approval process for these drugs, analysts say. This comes at a time
when FDA has stated its intent to increase OTC switches as much as 50%.

The rising prices of prescription drugs and pressure by government and
consumers to lower the cost of health care is prompting FDA to consider
more switches. But the agency is under increased pressure to consider
safety, as a result of health risks linked to the use of certain
prescription pharmaceutical drugs. The health-risk concerns have
extended to OTC drugs, with the most recent issue relating to Bayer
Corp.‘s Aleve, an anti-inflammatory drug sold over the counter. This
product has been linked to an increased risk of heart attack and stroke
in a National Institutes of Health study.

The process of switching prescription drugs to OTC status may become
slower in light of the focus on drug safety. Experts say switches will
continue to increase, though not at the rate that occurred in the past.

“Switches tend to come and go in cycles,” says Joshua P. Cohen, Ph.D.,
senior research fellow, Tufts University (tufts.edu). “In the mid-90s
there were plenty of switches, up to eight or nine a year. We will
probably not see that rate of switches in the near term.”

Generally, statins have established a record on safety and effectiveness
during their more than 15 years on the market, but FDA is being careful
because of risks that have been associated with the class. Bayer
(bayer.com) pulled its statin Baycol from the market in 2001 because of
a heightened risk of a very rare but potentially lethal muscle-wasting
side effect called rhabdomyolysis.

The committee voted against the Mevacor switch because the majority of
members believe that patients are better served with a
physician-controlled system with regard to all statins. Although
committee members agree that the safety and efficacy of Mevacor is not
in question, many members felt that patients are better served with a
system that provides more guidance to patients or a behind-the-counter
pharmacy strategy.

Many committee members said they would have voted for nonprescription
status had there been a behind-the-counter option as in the United
Kingdom. In that country, Merck (merck.com) received permission to
market its cholesterol drug Zocor over-the-counter. The United Kingdom
program, however, has pharmacists acting in an advisory capacity.
According to members of FDA’s Nonprescription Drugs and Endocrinologic &
Metabolic Drugs Advisory Committees, the OTC system in the United States
is not adequate for patients to make an appropriate assessment about
whether they require a cholesterol-lowering drug that would be used on a
chronic basis.

Almost at the same time that the Mevacor proposal was voted down, FDA
indicated a desire to expedite the process of switching products. FDA is
willing to review foreign data. According to Dr. Cohen, this may be a
boost for certain switch candidates, as other countries’ post-OTC
marketing experience would be evaluated before a U.S. switch.

OTC Pravachol work continues

Bristol-Myers Squibb (bms.com) intends to pursue FDA approval for an OTC
version of Pravachol 20 milligrams as a cholesterol-lowering treatment
option in the United States. Pravachol is approved in the United States
only as a prescription drug. The company has entered into an agreement
with Bayer HealthCare LLC for Bayer’s Consumer Care Division to handle
OTC sales and marketing for Pravachol 20 milligrams in the United
States, should FDA approve OTC use of the drug. Bayer was selected given
its experience in the cardiovascular category and the leadership
position the company has achieved in the marketing of the Aspirin brand.

A mature drug portfolio is one challenge that Bristol-Myers Squibb has
to face. Several top-selling drugs, including Pravachol and the cancer
drug Paraplatin, have been reporting lower sales because of
patent-exclusivity losses. The company estimates a loss of $1 billion to
$1.3 billion in sales per year between 2005 and 2007, putting downward
pressure on earnings.

Pravachol is indicated along with diet to reduce the risk of first heart
attack in patients with elevated cholesterol and recurrent heart attack
or a stroke in patients with heart disease, when diet and exercise are
not enough.

Dr. Cohen believes that the Mevacor decision will likely have a negative
impact on Pravachol. “I say this because the FDA’s decision to not allow
Mevacor’s switch had little to do with the specific product, Mevacor,
and more to do with the therapeutic category, statins, and the safety
factors associated with statin self-medication,” Dr. Cohen says.
“Without a behind-the-counter option, as is the case in Britain and
other European countries, statins will have a tough time making the
switch.”

According to business-information company Kline & Company
(klinegroup.com), the results of the advisory committee’s vote should
represent only a temporary setback for the cholesterol-lowering drug
class. Kline analysts say this category is still among the most likely
candidates to produce the first prescription-to-OTC switch in the United
States of a medication used to treat serious chronic but asymptomatic
conditions.

“With the soaring rates of high cholesterol among the American public,
there’s a very good chance that at least one of the many cholesterol
drugs being marketed now will switch in the next few years,” says Laura
Mahecha, industry manager for Kline’s Healthcare Practice. “Everyone
will be looking at the FDA’s final judgment on Mevacor very carefully to
see what they’ll need to do to get approved.”

For Bristol-Myers Squibb, Merck, and the other statin marketers, the
challenge in getting their statin products switched to OTC status is
convincing FDA that consumers will be able to understand how to use the
drugs correctly from a nonprescription label, and that they will be able
to accurately determine for themselves whether they are appropriate
candidates for statin therapy.

Kline analysts say the Mevacor application fell short in these areas,
and this is where other developers trying to switch drugs to OTC status
need to concentrate their efforts.

“Product labeling and limited indications will be key to get the right
people to self-select, but not everyone will pay close enough attention
to the small print on the package,” Ms. Mahecha says. “Warnings and
instructions on safe use will be included in product ads – and maybe
even quizzes to help show people if they’re supposed to take the drug or
not. But not everyone will see the ads or remember the warnings when
they go to purchase the drug.”

According to Kline, the challenge for drug makers is to produce a drug
that is powerful enough to be effective but does not attract people
outside its target audience. Canada and Great Britain addressed this
problem by providing the behind-the-counter drug classification. This
solution allowed Merck to get approval of its 10-milligram formulation
of Zocor for OTC use. Branded as Zocor Heart-Pro, the product has been
sold in the United Kingdom over the counter since July 2004.

“Behind the counter would be a good solution for statins and other
classes like diabetes and hypertension drugs, but for this to be created
on a nationwide basis, an act of Congress would be required, so behind
the counter is not likely to be implemented for several years, if at
all,” Ms. Mahecha says.

According to Ms. Mahecha, before making a decision on a statin OTC
switch, FDA and other countries’ health regulatory organizations will
look at outcomes data from the Zocor Heart-Pro switch in the United
Kingdom, looking for data such as reduced rates of heart disease and
financial savings from the switch for Britain’s Health Ministry. FDA has
never used foreign data in evaluating OTC switches.

Struggle for Plan B

FDA’s decision on Plan B’s OTC status was delayed Jan. 21. The agency
was unable to complete its review of Barr’s supplemental new drug
application to market the Plan B emergency contraceptive over the
counter by the Prescription Drug User Fee Act date of Jan. 21.

“Plan B is a special case, one in which the agency went against the
advice of the advisory committee,” Dr. Cohen says. “This will make the
switch eventually, provided labels are properly understood, etc. Again,
a behind-the-counter switch would work better than an OTC switch. At
this time, the U.S. does not have this option.”

FDA indicated to the company that the agency is committed to completing
its review of the application in the near future, and Barr remains
optimistic that the regulatory agency will approve Plan B for OTC sale.
Plan B continues to be available to U.S. consumers by prescription. The
company’s supplemental new drug application, if approved, would permit
the OTC sale of Plan B without a prescription for women 16 years old or
older. Barr would maintain the prescription status for women 15 years
old or younger.

Taken within 72 hours of unprotected intercourse, Plan B has been shown
to reduce the risk of pregnancy 89% after a single act of unprotected
sex. Effectiveness declines as the interval between intercourse and the
start of treatment increases. Plan B is more effective when taken in the
first 24 hours after intercourse.

Plan B is the first progestin-only emergency contraceptive. The
application seeking over-the-counter status for Plan B was filed with
FDA in 2003. In May 2004, FDA issued a nonapprovable letter offering
Barr the option of seeking dual status that would make the product
available over the counter for women 16 years old or older, and by
prescription only for women 15 years old or younger.

Plan B was approved as a prescription product by FDA in 1999. The
decline in efficacy from a delay in treatment is why a broad range of
health professionals believe that barriers to more timely access to Plan
B should be removed, including making the product broadly available
without prescription. Emergency contraception is available in 101
countries, 33 of which do not require a prescription. Emergency
contraception is available in some pharmacies without an advance
prescription from a physician or health-care provider in six U.S.
states, including Alaska, California, Hawaii, Maine, New Mexico, and
Washington.

Obesity drug moves toward OTC

Roche and GlaxoSmithKline are developing an OTC version of orlistat, the
active chemical in Xenical, in the United States. Roche (roche.com) has
concluded a deal to supply GlaxoSmithKline (gsk.com) with the active
ingredient for the new formulation. Roche retains all rights to market
Xenical as a prescription drug in the United States and all rights,
prescription and nonprescription, outside the United States.

“GSK’s experience in OTC switches, their marketing capability, and
expertise in consumer communications were the factors that helped us
identify GSK as our preferred partner,” says Franz B. Humer, CEO, Roche.
“Consumer Healthcare is a key part of GSK’s corporate growth strategy
and a perfect fit with our goal for orlistat to provide an ongoing
revenue stream.”

Xenical is approved by FDA as a prescription product for obesity
management and is marketed by Roche. Analysts believe there are
challenges to switching Xenical, as they relate to side effects.

The consumer health-care business of GlaxoSmithKline has a record of
creating new markets for over-the-counter brands. The company secured a
distribution agreement for Nicorette as a prescription smoking-cessation
brand and switched the product to its OTC status. The company then
in-licensed Nicoderm CQ smoking-cessation patch and successfully
launched the product as an over-the-counter patch first in the United
States and then in Europe and Australia. The company in-licensed and
launched Abreva as a direct-to-OTC drug for cold sores.