Event - Targanta and Theravance face short wait for final FDA decisions

The ongoing FDA anti-infectives advisory committee meeting continued in an unpredictable vein yesterday, with a panel of experts handing down a much more positive review of Theravance’s antibiotic telavancin than anticipated, while raising serious questions about Targanta Therapeutics’ oritavancin.

Briefing documents had suggested the opposite might be true, with a seemingly benign review of oritavancin prompting shares in the company to surge 33% on Monday. Meanwhile, prominent concerns about a perceived risk of birth defects with telavancin meant sterner words looked to be on the cards. This all makes the FDA’s final decisions, due in the next two months, much harder to call, but the most likely outcome for the former looks like a complete response letter with a request for further trials, the prospect of which sent shares in Targanta plunging 83% in early trade to a record low of $1.33.

Two oritavancin studies had been submitted for review, one of which was conducted several years ago and was the main cause for concern. The panel questioned whether it presented an accurate picture of efficacy against more virulent bacteria which have become increasingly common since the study was conducted, between 1998 and 2003, particularly with regards to MRSA infections. They also pointed out the study was fairly small in size.

The panel voted 8-10 against that the older study established the drug’s efficacy, on the more recent trial the votes went 11-6 in favour. Overall, the vote was 8-10 against that the data demonstrated the safety and effectiveness of oritavancin for the treatment of complicated skin and skin structure infections (cSSSI), the indication in focus at this advisory committee.

Limited label?

Oritavancin has a PDUFA date of December 8, and on a conference call today Targanta’s chief executive, Mark Leuchtenberger, said he had not ruled out approval, considering the more encouraging FDA review. However, that seems a highly optimistic stance. One possibility is approval without an MRSA label, which although incrementally positive would severely limit commercial potential.

The company is already preparing for another phase III trial of the drug, but will wait to hear the FDA’s conclusions before finalising the design. Hopes for the drug were high because of its more favourable, shorter dosing schedule, which would position it well in the market, and benign side effect profile compared to telavancin. However, unless it can establish strong efficacy against the most virulent of infections, the regulator would seem to have little room to approve it with a broad cSSSI label on the current data. 

Another problem facing Targanta is its funding situation. Cash stood at $42m at the end of the third quarter, enough for another 9-12 months, but it is an issue that is going to have to be addressed in the very near future, particularly if a phase III trial is to be paid for.

Although Targanta may have failed to establish conclusively oritavancin's efficacy, trial results published since the drug was submitted to the FDA indicate the antibiotic still has the potential to win approval in cSSSI at some point. How the company gets to that point remains to be seen.

Looking for a saviour'

Targantas share price reaction suggests investors would be unwilling to stump up any much-needed cash. The company may have to follow Theravance’s example and find a partner for the project, if it can; Astellas has worldwide rights to telavancin, and the companies will jointly market in the US. This sharing of risk may be one reason the advisory committee meeting has not prompted the massive swing in Theravance's stock price as has been seen in Targanta and Arpida, the victim of today’s meeting.

Theravance shares fell 5% in early trade today to $6.50, despite the positive review, with investors maybe mindful of the FDA’s sharp focus on safety, and unpredictable nature. A positive advisory committee vote does not necessarily mean a marketing license is in the post, even though things are looking encouraging. The panel voted 21-5 that the data presented established the drug’s efficacy and safety in cSSSI.

Responding to a perceived risk of birth defects, the experts concluded that in extreme, life threatening situations the benefit of the drug outweighed risks in pregnant women, voting 18-5 in favour. However, they were almost unanimous in recommending a risk management strategy be implemented to prevent unintended use of the drug in pregnant woman.

Nothing is certain

Concerns about telavancin side effects, most notably kidney problems, has been responsible for lowering expectations among investors that the drug will win approval, and a black box warning remains a distinct possibility. However, the panel members seemed more concerned about mounting resistance to the limited antibiotic options available to treat tough MRSA infections, viewing televancin as a valuable new weapon.

Whether the FDA agrees with that emphasis remains to be seen, but approval alongside a risk-management plan now looks like a strong possibility. With a decision due before the end of January, there is a not long to wait.

However, if one thing is certain about the FDA approval process, it is that nothing is certain, and neither Theravance nor Targanta will be making big decisions about the future just yet.

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