Healthy Skepticism Library item: 263

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Publication type: news

Zimmerman R.
New Ways to Take Old Drugs: Help Patients, Extend Patents
The Wall Street Journal 2004 Mar 15

Full text:

The drug naltrexone was supposed to take away Frank Philip’s desire to drink. Approved in 1984 to treat opiate addiction, it became a treatment for alcohol dependence a decade later and removes the urge to drink excessively.

But Mr. Philip didn’t take it consistently and that led him to return to imbibing again and again.

“There were a few periods of relapse,” says the 66-year-old Bostonian.

In fact, naltrexone has been a bust, doctors say, mainly because patients such as Mr. Philip didn’t take it as prescribed. But now, a biotechnology company is resuscitating the drug with a clever twist: an injectable version that lasts one month, removing patients’ ability to change their minds every day. The experimental new formulation, called Vivitrex, is released in a constant dose by injection, avoiding the surge of medication followed by a drop when taken as a daily pill, and is now in late-stage tests conducted by Alkermes Inc. of Cambridge, Mass.

Vivitrex is just one of a panoply of medications getting a new life through the science of “drug delivery.” Some 47 biotechnology companies nationally, and a slew of academic researchers, are working exclusively on drug delivery, a field that has advanced far beyond early well-known innovations, such as the nicotine patch for smokers. Today, new drug-delivery methods are elping schizophrenics stay on their medication; compressing three Ritalin pills into one; and — if an experimental technology works — even enabling a nasal spray with near-instant effect for alleviating sexual dysfunction.

New drug-delivery techniques are also a way for pharmaceutical companies to extend their patents. For instance, patents for naltrexone, marketed for alcohol dependence through a unit of DuPont Co. under the brand name ReVia, expired in 1998, after which several companies began selling a generic version. If approved, Vivitrex — like most new drugs — would have patent protection for seven years. With these new formulations, says Needham & Co. analyst Mark Monane, “what’s old is new again.”

A six-month study of 624 patients found that Vivitrex significantly reduces heavy drinking, defined as more than five drinks a day, in men. With the highest studied dose of the drug, heavy-drinking episodes among males fell to an average of three days over a one-month period, down from a previous average of 19 days. That was 48% better than the study group getting a placebo injection; both groups got psychotherapy. Women on Vivitrex, however, did no better than those in the control group.

“Alcoholism is a disease that corrupts the brain’s sense of self-preservation and creates the conviction that drinking again can be good,” says David Gastfriend, director of the addiction-research program at Massachusetts General Hospital in Boston. Dr. Gastfriend, who is involved in the Alkermes trial, adds: “The fact that an injection is still working a month later cements the continuity of treatment and the benefits.”

Alkermes says it will file for Food and Drug Administration approval to market Vivitrex in the first half of next year.

Another fertile area is schizophrenia, where up to 80% of patients skip doses or stop taking medicine altogether, putting them at risk for hospitalization or even suicide. Johnson & Johnson’s Risperdal, approved in 1993, was one of a new wave of blockbuster antipsychotic medications that some doctors say revolutionized treatment of the disease by reducing side effects. A new, injectable version called Risperdal Consta, marketed by J&J with Alkermes’s technology, involves one shot every two weeks of tiny microspheres that dissolve to release the drug slowly. Risperdal Consta, approved in October, is expected to have sales of up to $500 million within five years, says Matthew Dodds, an analyst with SG Cowen.

Drug-delivery scientists are also working in the lucrative area of sexual dysfunction. The drug apomorphine, discovered in 1868, stimulates dopamine receptors in the brain that are responsible for initiating erections and other sexual responses. The drug is sold in Europe, but has not been licensed in the U.S. largely due to side effects including vomiting, nausea and fainting.

But a new nasal spray, under development by Nastech Pharmaceutical Company Inc., of Bothell, Wash., delivers the drug directly to the bloodstream, making a lower dose possible, with fewer side effects. The drug also takes effect within five or 10 minutes, compared with the nearly one hour it takes for Viagra to work, says Nastech Chief Executive Steven Quay.

Nastech is also testing apomorphine in women, and using its nasal-spray technology in early tests of an obesity medication, called PYY. A naturally produced hormone, PYY signals a feeling of fullness.

Sometimes, the aim of drug-delivery technology is for convenience. Concerta, a morning, once-a-day version of Ritalin for kids with attention deficit and hyperactivity disorder has eclipsed the older three-pill-a-day regimen.

Concerta, manufactured by J&J’s Alza Corp. unit, has a pill coating that dissolves in an hour, releasing an initial dose of the active ingredient, methylphenidate. The rest is released slowly over the course of the day.

Concerta — which also reduces opportunities for illegal selling of tablets — is now the top-prescribed medication for ADHD, with over $614 million in U.S. sales last year, according to research firm IMS Health.

On another front, a highly experimental drug-delivery system that is now being tested in animals could ultimately improve cancer therapy.

At the University of Pennsylvania, Dennis Discher, professor of chemical and biomolecular engineering, is testing smaller-than-microscopic “nanoscale polymer devices” that mimic viruses. The polymer-based devices insert themselves into cells and release drugs. The cancer drug Taxol, for example, could be released directly into targeted cells, likely causing fewer side effects than the current oral version, which has side effects that include nerve damage.

In the long run, changes in drug delivery may make daily pills obsolete for certain disorders. Steve Siegel, a psychiatrist at the University of Pennsylvania’s Stanley Center for Experimental Therapeutics in Psychiatry, is currently testing a surgical implant, a small disk placed under the skin, to deliver schizophrenia medicine for one year.

The removable implant currently uses the older schizophrenia drug, Haldol, but could be adapted to hold other medications. It dissolves slowly to release medicine. The new formulation, now in animal testing, would “take all the forgetting, all the logistics out of the equation,” Dr. Siegel says.

However, some think an implant that lasts a full year may be taking the concept too far. “This is the road to involuntary medicating,” says Vera Sharav, a patient advocate and president of the Alliance for Patient Research Protection. “Do you know how much suffering would have to go on before it’s removed? It could be used in prisons, in hospitals, wherever.”