Launch of Avandia and Actos
June 1999: SmithKline Beecham launched Avandia (rosiglitazone),
its new oral treatment for non-insulin dependent "Type II"
diabetes. It is being co-promoted by Bristol-Myers Squibb, and
is indicated as both monotherapy and in combination with Bristol-Myers
Squibb Glucophage (metformin), licensed from Merck KGaA. Recommended
for approval in the United States at the end of April, Avandia
is currently pending approval with the EMEA in Europe and 13 other
markets. The FDA also recommended the approval of a similar drug
from Takeda, Actos (pioglitazone), which will be co-marketed in
the US by Eli Lilly.
Both Avandia and Actos are members of a new class of drugs known
as thiazolidinediones, commonly referred to as the "glitazones".
These oral drugs target insulin resistance, the inability of the
body to respond adequately to insulin. This leads to poor control
of blood-sugar levels, even if natural insulin production is normal.
Potential Impact on Rezulin in the US
These two new drugs, both marketed by large companies experienced
in the diabetes market, are likely to impact sales of the first
glitazone launched, Warner-Lambert’s Rezulin (troglitazone). Licensed
from Sankyo, Rezulin has been subject to a review by the FDA following
reports of serious side effects, and doctors have been advised
to limit their prescriptions. Similarly, even though Avandia is
given in lower doses and is metabolised much faster, the FDA has
ordered monitoring of patients as therapy begins.
Troglitazone in Europe and Japan
Sankyo’s European licensee for troglitazone, Glaxo Wellcome, was
unsuccessful in its attempts to re-launch its product Romozin
in the UK in March 1999. The company withdrew the drug shortly
after launch in December 1997, due to concerns over liver toxicity.
This was despite submitting additional safety and efficacy data
to the UK’s Medicines Control Agency in August 1998. It is now
unlikely that GW will resubmit troglitazone in the UK, as the
company has its own non-glitazone Type II diabetes drug in phase
II trials. Sankyo is continuing to sell the product in Japan,
as Noscal.
Avandia vs Actos?
Many analysts believe that Actos has the most promising competitive
profile of the three drugs. Avandia is perceived as being superior
to Rezulin, but disadvantaged by its lipid profile (it causes
an increase in LDL-cholesterol levels, not seen with Actos). SmithKline
Beecham, however, maintain that HDL, or ‘good’ cholesterol levels
rise as well, meaning that the overall effect on the lipid profile
is neutral. Also, Actos is now approved for use with sulfonylurea
and insulin, whereas this data for Avandia is still a few months
away.
It is estimated that the market will be worth over $5 billion
by 2003, with Actos capturing $3 billion. By mid-2000, Actos is
expected to have up to 20% of the US oral diabetes drug market,
and Avandia 15%, whilst Rezulin’s share will fall to below 5%.
Another benefit of Actos is its once-a-day dosing, whereas Avandia
is more efficacious if administered twice-daily. However, SmithKline
Beecham and Bristol-Myers Squibb benefit from larger sales force
sizes. Avandia’s competitiveness has been assured by its pricing,
which will be 8-15% lower than Rezulin. The label recommends regular
liver testing, but it does not contain the black-box warning of
Rezulin. After the ADA meeting, where efficacy data for Actos
was presented, it appears that Avandia and Actos appear to be
similar in terms of efficacy, weight gain and oedema.
Epidemiology/Cost of Treatment
Approximately 2.3% of the world’s population suffer from some
form of diabetes, with the number growing by 4-5% per annum. Significantly,
the launch of the glitazones will raise public awareness, and
narrow the "huge" gap between prevalence and treatment
rates. Around 50% of the Type II population are currently believed
to go undiagnosed. Even so, diabetes costs the UK’s National Health
Service 5.5 - 9.4% of its total annual budget, and, in the US,
the disease cost $98 billion in 1997.
Further scientific information on the glitazones and other oral
diabetes therapies can be found on R&Dfocus.
For more information about SmithKline Beecham, Eli Lilly, Takeda
etc., see the relevant IMS HEALTH Pharmaceutical
Company Profiles.
