Analysts fear severe delay for Arpida antibiotic
antibiotic will be approved by industry regulators, according to
one analyst's report.
The doubts over iclaprim now sown into the minds of those at Swiss firm Landsbanki Kepler has led analyst Dr Denise Anderson, to declare that the company is only worth two thirds of its current price. She set a target share price of CHF22 (€13.45) compared to a cost of CHF32.90 at the time of the report. The news clearly hasn't affected, or yet reached, investors yet and in the few days since Landsbanki Kepler's assertion, the share price is still holding strong today at CHF34.25. The analysts teased their information out of two abstracts for presentations on iclaprim Phase III results, due to be given at the Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) in September, and October's meeting of the Infectious Diseases Society of America (IDSA). "Both Phase III trials for antibiotic iclaprim met their primary endpoints, according to Arpida. However, details being released now raise serious questions in our mind about whether the drug will be approved with current data," said Dr Denise Anderson. The information that has got Anderson "worried" is by how much iclaprim was shown to be non-inferior to Pfizer's Zyvox (linezolid) - the primary endpoint of both trials. Essentially, Arpida has chosen an unusual trial design where iclaprim was considered to be non-inferior to Zyvox if its eradiation rate was not more than 12.5 per cent worse than Zyvox, with 95 per cent confidence. "However, EU guidelines require a fixed delta of 10 per cent (a tougher test than a level of 12.5 per cent) in most cases, and the FDA seems to be moving to the 10% level as well," said Anderson. The confidence interval used also means that the test stays below zero - the point at which the two drugs could be said to be equal. She went on to point out that this set up for a non-inferiority trial has previously been dismissed as "puzzling" in one journal and may cause the FDA to think twice about approval. Arpida remains unconcerned though, and disagrees with this assessment of its trial design, saying: "The assessment of the importance to crossing zero is controversial since such a request would 'punish' highly powered studies." The lowered share price reflects the fact that there is a "very high" risk that any approval for iclaprim will be delayed, according to Anderson. "This is especially the case as iclaprim does not appear to have any important safety advantages versus Zyvox and as the FDA has delayed almost all recent antibiotic approvals, sometimes for years," she said. She also noted that if the drug never succeeds in gaining approval: "we estimate that Arpida is worth around CHF11 per share." Iclaprim is designed to block folate synthesis, which is necessary for DNA replication. An oral formulation of iclaprim is also currently in Phase I trials. Since development of this new formulation should be faster, the drug is estimated to only be between 12 and 18 months behind intravenous (IV) iclaprim. This potential oral option sets the drug apart from other antibiotics, with Zyvox and garenoxacin the only two potential rivals left with both an IV and oral form. However, garenoxacin, developed by Schering-Plough and Toyama, has also been delayed. It is currently in Phase III trials in Japan, but the US and EU filings have now been withdrawn - a year ago and only a month ago respectively. EU regulators said they weren't sure the drug was effective enough to be approved, leaving Schering-Plough considering its options. Zyvox was the first in a new class of antibiotics - the 'oxazolidinone' class, whereas garenoxacin is in the 'quinolone' class and iclaprim, the 'diaminopyrimidine class'. Should the IV version be delayed, at least Arpida has a good chance to get it right second time round.
