Hottest Drugs in FDA Pipeline Often Get Stuck There for Years

  • Capital Connections ®
  • -
  • 07/1980

by Karen Feld

Washington(INA) – When Dr. Bernard Abrams, a Columbus Ohio, optometrist and wealthy industrialist and his wife adopted a happy and healthy baby girl nine years ago, they had no idea of how much their life would change. 

At age 6, Felice Beth was suddenly stricken by convulsions, with 75 to 100 seizures a day.  She had developed myoclomic epilepsy – a severe form of epilepsy that, in all of its varieties, affects about one million Americans. 

“Kids were dying all over the country from this disease,” says Abrams, “but they’d be reported as drowning in the bathtub.”

The Abrams’ financial resources gave them medical options many other people would have lacked.  After weeks of heartache and medical consultations, says Abrams, “The most realistic recommendation was to prepare her for an institution.  The most optimistic was that maybe she would survive and be retarded.”

The Abrams’ discovered that sodium valproate – the drug most effective in treating this ailment – was not available in the United States, although it had been marketed in France for 11 years and in England for six, with successful results. 

Three years ago, Abrams flew his daughter to England, where she began treatment with sodium valproate.  Felice Beth is now seizure-free and leads a normal life, attends the third grade, recently played a flower girl in “The Wizard of Oz” and rides her bike after school. 

As a result of Abrams’ crusade and an intensive media campaign, sodium valproate, manufactured by Abbott Laboratories, won FDA approval faster than any drug in history.  Since its introduction in the United States in February 1978, it has controlled about one million seizures per year. 

This is only one example of the new so-called “miracle drugs” available abroad that patients long have been denied in the United States – the world’s most technically advanced nation. 

Gaining FDA approval is a lengthy process; the average time required is 20 month, according to the General Accounting Office, the investigatory arm of Congress.  In fact, it often takes six to eight years, or longer, to gain FDA approval, according to the Pharmaceutical Manufacturers Association.  For example, the drug propranol – an important new treatment for high blood pressure – was available in England for seven years before it was introduced in the United States in 1976.

The FDA assesses both risks and benefits before approving new drugs. On one hand, this protects U.S. consumers from the potential dangers of premature drug approval, which might lead to hazardous or fatal side-effects.  No one wants another thalidomide or MER-29 (the drug that was marketed to reduce blood cholesterol levels, but caused blindness).

On the other hand, new drugs frequently are delayed unnecessarily for years, during which time many lives might be saved. 

“There is always a cost-benefit or cost-risk assessment associated with any drug or treatment,” says Dr. Kurt Isselbacher, professor of medicine at Harvard Medical School. “There is nothing we do and no medication that we take that will not at some time in some patient result in adverse effects.  There is no utopia as far as drug prescriptions and administration is concerned,” he adds.

Fourteen important new drugs were approved in this country between 1975 and 1978. With only one exception, these drugs were available in other industrialized nations from two months to 12 years earlier.  Of the major developed countries, only Sweden has a longer drug approval process than the United States. 

More than 70 new drugs available abroad are unavailable to U.S. patients, according to the House Appropriations Committee.

“By today’s standard, oral contraceptive would never be approved,” says Rep. James Scheuer, D-N.Y., a member of the House Science and Technology Committee, which requested a GAO investigation of the drug lag.

The cost of developing and marketing a new drug in this country is about $60 million.  Although many of the new drugs are developed by U.S. Firms (74 out of 339 drugs discovered worldwide between 1973-77), the United States ranks ninth in introducing them, and this figure continues to decline. 

“The true minorities in this society are those people who do not have an advocate because they have an ailment that is 10,000 or 20,000 people,” says Abrams. “There is more money in bringing out orange-colored aspirin where you have a market of five million than there is for bringing out a drug where the market is 20,000 or 100,000,” he adds.

One promising new drug in the FDA’s “investigational new drug stage” (IND) is chenodeoxycholic acid, which is said to dissolve gallstones, greatly reducing the need for surgery.  The irony is that a successor compound, ursodeoxycholic acid, is more effective and has fewer side effects.  By the time cheno is approved in the United States, it probably will be outdated and superseded abroad by urso, says Dr. William Wardell, of the Center for the Study of Drug Development, University of Rochester Medical Center.

The United State offers no motivation to develop drugs like this, says Abrams, because surgery is a highly profitable business.

Millions of U.S. heart patients may not have to wait as long to benefit from two new cardiovascular drugs, verapamil and nifedipine, both useful in treating heart attacks. The FDA has received new drug applications (NDAs) for both and the drugs now await efficacy and safety approval, which could be months – or years – away. 

But nifedipine, at least, has been available in Europe and Japan for six years.  It prevents the contraction of muscles inside the heart’s arteries which can cause intense pressure and it has been shown to have little effect on similar muscles in other parts of the body. It is now being tested on cases of classic angina, says Dr. James E. Muller, a cardiologist with the Harvard School of Public Health, who has been researching the drug. 

The United States was the last developed country to approve beta-blockers – nitroglycerin compounds that are used to relieve angina attacks, but which do not reduce their frequency.  Sweden has approved alprenolol, a beta-blocker that has been shown to prevent death after heart attacks, but the drug is not under study in the United States. 

One of the most promising new drugs is isoprinosine, an oral anti-viral drug developed in 1969 by Newport Pharmaceuticals, a relatively small California drug company.  Although viral diseases are among the most common human afflictions – ranging from the common cold to rubella, hepatitis, and herpes – only a few anti-viral drugs are available anywhere in the world.  Isoprinosine currently is sold as a broad-spectrum anti-viral agent in more than 40 foreign countries, including the Philippines, Mexico, Argentina, Peru, Kora, Greece and West Germany. 

But isoprinosine is still being tested in the United States; it is past the IND stage and considered in intermediate status, according to FDA spokesperson Fay Peterson.  “But,” she added, “it is not near approval. Efficacy trials could take some time.”

Trials to prove the drug’s efficacy in treating SSPE, a rare and usually fatal measles encephalitis, will get underway first. Limited approval of the drug probably will be granted in this area before it is approved for broader anti-viral use.

Antidepressants such as maprotiline and viloxazine, which don’t cause death in overdose, have been available in England since the mid-1970s, but are not available in the United States. These drugs have fewer side-effects than the tricyclic drugs available in this country.  Another drug, cyproterone, which is useful in treating male sexual aggression also has been available in England for some time.  There is no equivalent in the United States. 

DMSO (dimethyl sulfoxide) has the potential for treating a range of ailments, including arthritis and shingles (for which there is no effective treatment in the United States), and reducing intracranial pressure in head injuries.  It has been claimed by those who use it to be safer than aspirin and more effective as an analgesic.

“DMSO is the aspirin of the 21st Century,” says University of Oregon professor Dr. Stanley Jacob, who has supplied it to the Atlanta Falcons and other pro ball clubs.  It reduces pain and heals bruises.  It is not only valuable alone, but since it is absorbed rapidly into the skin it acts as a vehicle to carry other drugs, such as antibiotics, into the bloodstream within seconds.

Although the drug, which smells like garlic and tastes like oysters, is legal in 12 countries, including Great Britain, and has been legalized for veterinary use in the United States, it does not yet have FDA approval.  Even so, its use is widespread in nursing homes and in football locker rooms – as long as it is administered by a physician.

The House Select Committee on Aging, which held hearings on DMSO last spring, concluded that the drug was beneficial in treating soft-tissues injuries.  The findings were based on testimony from team physicians (including Dr. Graham Reedy of the Oakland Raiders and Dr. Marvin Paul of the Toronto Maple Leafs), pro ball players (including the Raiders’ Ben Davidson, Houston Astros’ Dave Roberts and Dallas Cowboys’ Randy White), and Dr John Baum, director of arthritis, Monroe Hospital, Rochester, N.Y. Even U.S. congressmen, including Steve Symms, R-Idaho, testified to using DMSO with positive results.

Rep. Claude Pepper D-Fla., chairman of the House Select Committee on Aging, has recommended that the FDA legalize DMSO for non-controversial uses, such as an analgesic, and effectiveness studies in other areas be escalated.  He introduced legislation which calls upon the National Institute of Arthritis to undergo tests and report back in one year. 

Pepper would like to see the Interstate Commerce Commission license drugs not thought to be patentable for a limited period of time, in an attempt to allow the drug company to make some profit which would be an incentive for it to conduct tests. 

The FDA asked Research Industries Corp., a small Utah company, to prepare new protocols to test DMSO.  That company was successful in 1978 in getting FDA approval for DMSO for use against bladder condition, called intestinal cystitis, but the potential of the drug is far greater.  

“The speed with which the FDA approves important drugs has been a frequent target of criticism by drug manufacturers, by physicians and by consumers,” says Rep. George Brown, D.-Calif., chairman of the Science Research and Technology Subcommittee of the House Committee on Science and Technology.  Brown feels there should be more effective congressional oversight. 

After reviewing a recent GAO study on the drug lag, Rep. Scheuer has four recommendations.  First, the FDA should consider foreign research, which is developed under the same criteria that is applied to U.S. institutions and studies.  This would save not only time, but millions of dollars used to duplicate those results in the United States. 

Second, he suggests reducing the involvement of the FDA in the early stages of clinical tests, a source of the delay.  This has proven successful in Great Britain. 

Third, he suggests an attitudinal change to improve relations with sponsors of NDAs; perhaps an ombudsman could monitor the progress of the applications. 

Fourth, he recommends some method of post-marketing surveillance which would make it less risky for the FDA to approve limited use of a promising new drug.  For example, if a particular epileptic child is allergic to all available drugs, but could be helped by a drug which has been approved abroad, but is still undergoing tests in the United States, it may be beneficial. 

“The FDA seems unable to bite the bullet and make a decision that a particular doctor could use a particular drug in a particular situation,” says Scheuer.  “There ought to be more reliance on brains and wisdom outside of government, in universities and medical schools, and there ought to be less of this arrogant assumption that all wisdom lies within the FDA,” he adds. 


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