Here's what GLX's withdrawl has done to a diabetes article that I expected to be upbeat (it's in tomorrow's London Financial Times):
Diabetes: Bitter pill for insulin users
TUESDAY DECEMBER 9 1997
The withdrawal in the UK of a promising diabetes drug is a blow for sufferers
worldwide, Victoria Griffith reports
Glaxo Wellcome's decision to withdraw Troglitazone from the UK market is a
significant blow, not just to sales of the drug, but also to the hopes of diabetes
sufferers worldwide anxious for innovative treatments.
Troglitazone - discovered by Sankyo in Japan and known by the brand names
Noscal there, Rezulin in the US and Romozin in the UK - is one of a new
class of drugs called "insulin sensitisers", that were hailed as a promising
weapon against diabetes before Glaxo's announcement.
"The insulin sensitisers are state-of-the art for this disease," says Camilo
Leslie, professor at the University of Miami's Diabetes Research Institute.
"There is very little else in the pipe- line."
Glaxo Wellcome suspended marketing of Romozin because of a
higher-than-expected incidence of liver malfunction in 147 of 370,000 patients
taking the tablets.
The US Food and Drug Administration has allowed sales in the US to
continue, but has warned users to monitor closely the drug's side-effects.
The pills, administered to 600,000 American patients, have proved
enormously successful since their March approval in the US, where they are
marketed by a division of Warner-Lambert.
Questions about Troglitazone have now thrown a shadow over the entire class
of insulin sensitisers. Researchers and patients had been excited about what
looked like a reasonably full pipeline of new products.
Sugen and Ligand, the US-based biotechnology companies, are working on
insulin sensitisers, with Ligand in phase II clinical trials. Some scientists also
include Glucophage, the Bristol Myers Squibb drug licensed from Lipha, the
French group, and introduced in the US in June, in the category, although the
exact mechanism of that product is unclear.
Rising rates of diabetes in the US have added urgency to the drug
controversy. At the end of October, the Centres for Disease Control in
Atlanta warned that the disease was turning into a national epidemic, with a
record 16m Americans diagnosed.
Higher levels of obesity and an ageing population are thought to be the main
causes. The disappointment over Troglitazone is exacerbated by the recent
suspension of Fenfluramine, the obesity drug popularly known as fen-phen,
which many diabetics were using to control their weight.
Insulin sensitisers present a new way of treating diabetes, because they
address the underlying causes, rather than merely the symptoms of the
disease. Diabetes impairs the body's ability to convert sugar (glucose) to
energy. Insulin is the hormone that normally allows this conversion to take
place.
Traditionally, treatments for the disease have focused on increasing the amount
of insulin in the body. Pills marketed by companies like Hoechst, Novo
Nordisk, Upjohn and Pfizer boost production of the hormone. This makes
sense for those with Type 1 diabetes, an auto-immune disease that strikes
adults and children. In Type 1 diabetes, the body's immune system becomes
confused and begins to destroy its own insulin-producing cells.
It was long believed that Type 2 diabetics, who contract the disease in
adulthood, also suffered from insufficient insulin production. Scientists now
believe, however, that Type 2 patients have normal or even above normal
supplies of the hormone; their bodies simply fail to make proper use of it.
Insulin sensitisers address this problem by making the body more receptive to
the hormone.
Troglitazone, discovered by serendipity before scientists understood much
about the way it works, stimulates specific nuclear receptors in liver, muscle
and fat cells that regulate the production of insulin-responsive genes.
Ligand hopes to improve on the drug by adding another, similar receptor to
the mix. "We believe a two-sided approach will prove even more effective,"
says Andres Negro-Vilar, chief scientific officer of the company.
Insulin sensitisers are not the only diabetes drugs under research. The
biotechnology group Megabios is developing gene therapy approaches to the
disease. At the end of October, researchers at Massachusetts General
Hospital said they had identified a new set of genes responsible for diabetes,
paving the way for more progress. Yet genetic therapy approaches and
treatments based on the MGH discovery are probably at least a decade from
the market.
Researchers have not given up on the insulin sensitisers. "The number of
people with liver complications from the disease in the UK was low," says
Simeon Taylor, head of the diabetes department of the US National Institutes
of Health. "I'm not saying the product should not have been pulled. But it may
turn out to have a side-effect that strikes few patients."
Insulin sensitisers have exhibited unwanted side-effects in the past. Two
promising drugs, Ciglitazone and Pioglitazone, were dropped from research
because of toxicity and neurological defects.
One of the main challenges in fighting diabetes is that it is often not taken
seriously. "It's a chronic disease, which by definition means it is not usually
immediately life-threatening," says Rubin Bressler, a professor of medicine at
the University of Arizona. "Toxicities in drugs to address it are not much
tolerated by regulators or patients."
Hard-to-change lifestyles complicate matters; many diabetics fail to exercise
more and eat fewer sweets, even after diagnosis. Because sufferers may not
feel ill in the disease's early stages, the temptation to delay treatment, or fail to
comply with recommended regimens is strong.
The long-term consequences of diabetes, however, can be dire: blindness,
neurological problems, liver failure and, in a number of cases, death. That, and
the growing incidence of the illness, has turned the search for treatments into a
high-stakes match. |
