FDA Avandia alert raises new safety questions

The news of the Cleveland Clinic's study released this week, which found that patients taking GlaxoSmithKline's (GSK) Avandia (roseglitazone) were 43 per cent more likely to have a heart attack than those given other drugs, has been supported by existing warnings from the FDA dating back to 2001.

In March 2000, a diabetes expert from the University of North Carolina, Chapel Hill, wrote a letter to the FDA complaining about the GSK's "rampant abuse of clinical trial data" related to Avandia's cardiovascular safety.

The letter, which is on the FDA website, along with warnings provided by GSK's own advisers before Avandia reached world markets, demonstrate a pre-existing concern over the drug's affect on heart function.

According to media reports, the lawyers of individuals claiming damages against GSK regarding Avandia would use the letters to demonstrate that GSK had previously failed to disclose the risks of heart problems associated with Avandia.

Since the Cleveland study was published in New England Journal of Medicine (NEJM), GSK's shares have fallen about 13 per cent, which is equivalent to almost GBP 1bn pounds (USD 2bn) in market value. Merrill Lynch analysts downgraded GSK's stock to "Sell" from "Neutral" on 30 May.

Prescription data unclear
Avandia is GSK's second best-selling drug, with FY06 global sales of GBP 1.6bn (USD 3.2bn), which accounted for seven per cent of total group revenues. An Impact RX report indicates Avandia's share of the market for newly prescribed oral anti-diabetics fell to practically nil from around 10 per cent in the two days after the NEJM article was published.

Deutsche Bank analysts said that while two days of prescription data does not identify a specific trend, investor reaction is worse than anticipated and suggested that there could be as much as 22 per cent downside risk to GSK's near-term earnings, with further falls expected for shares. The stock fell as much as 2.6 per cent to a two-year low of GBP 12.99, which makes it the top FTSE 100 loser in a fairly buoyant London market.

Commenting on the fall in US prescriptions, GSK insisted it was too early to identify any trend: "Two days of data is not enough to reach sensible conclusions on the trend for Avandia new prescriptions. The meta-analysis published last week, whilst not rigorous enough to reach conclusions about adverse events, has generated significant negative and erroneous publicity. However, we remain confident that the significant benefits of Avandia continue to outweigh any treatment risks."

Deutsche Bank analysts said new and switch prescription data from 1,900 US doctors showed Avandia's average share of the newly written OAD prescription market from 21 to 23 May was 10, eight and six per cent respectively.

ImpactRx disagrees with Deutsche Bank's interpretation of its data: "We believe insufficient time has elapsed since publication and it's premature to conclude any dramatic or lasting changes in physician prescribing behaviour at this point."

Takeda's Actos steals market share
At the same time, the rate of patients switching from one drug to another was three times the usual level, with Takeda's competitor product, Actos' (pioglitazone) share of the new prescription market increasing from 10 to 22 per cent.

Takeda is Japan's largest pharmaceutical company and reported a 7.2 per cent increase in FY06 profits, caused by higher US sales of Actos. Sales forecasts for Actos may be revised for FY07, as a result.

Takeda shares reached a two-month high on 30 May after the Deutsche Bank report. The stock gained 1.1 per cent (JPY 90) to reach JPY 8,020 on the Tokyo Stock Exchange.