The stock market reaction to FDA briefing documents on Targanta Therapeutics’ oritavancin and Theravance’s telavancin, two new antibiotics which will be discussed at Wednesday’s advisory committee meeting, suggests that hopes for their ultimate approval have risen.
Targanta surged 33% yesterday, while Theravance climbed 7%, as the regulator’s initial review of the two applications appeared to come to the conclusion that both drugs were as effective as vancomycin, currently the strongest MRSA-fighting antibiotic on the market. Concerns about the safety profile of telavancin probably capped gains in the latter.
Both drugs are seeking approval in complicated skin and skin structure infections (cSSSI). Mostly caused by MRSA bacteria, cSSSIs range from fairly simple abscesses to hard-to-treat diabetic foot ulcers, and growing evidence of resistance to vancomycin means new treatment options are needed.
Black box warning?
Theravance, which has signed up Astellas Pharma as a marketing partner, has already received one approvable letter for telavancin, related to problems found at several clinical trial sites. Encouragingly, the documents released yesterday indicate the regulator is willing to disregard data from those sites, and consider the remaining evidence.
However, the documents did highlight some safety concerns fairly prominently, particularly an imbalance of kidney disorders in the telavancin group and worries about use of the drug in pregnant women.
Studies in animals, which observed malformations of foetuses, were flagged and a recommendation from the FDA’s Maternal Health Team was included, advising that that the drug is not used in pregnant women, and that a black box warning should go on the label, and post marketing surveillance conducted.
The oritavancin review appeared to be more positive overall. The FDA documents concluded that the outcomes for oritavancin and vancomycin patients with cSSSI were comparable in subgroup analyses for age, gender, ethnic group, region, and disease category, in terms of both safety and efficacy.
The major concern that has dogged oritavancin recently is the non-inferiority (NI) margin the company chose in one of the two pivotal trials conducted. The NI margin is used to compare the effectiveness of new antibiotics to standard treatments, but lack of clear guidance as to what margin is suitable for cSSSI trials from the FDA has created uncertainty.
The subject will be discussed today, ahead of the specific review of the two antibiotics tomorrow. Briefing documents released last week on the matter indicated that the margins Targanta used, 10% and 15%, will be acceptable; concern that 15% was too high was the main fear. (Event - Pathway to approval for new antibiotics set to become clearer, November 13, 2008).
Of course the FDA does not have to follow the advice of its advisory committees, but with a seemingly benign review of oritavancin and encouraging guidance on the approval pathway for cSSSI antibiotics, investors have good reason to feel more cheerful about the prospects of Targanta. Shares in the company edged higher again in early trade today, to $8.55, a six-month high.
The table below illustrates consensus forecasts for late-stage anti-MRSA antibiotics. Clearly, Basilea’s Zeftera, to be promoted with partner Johnson & Johnson, is seen as a clear winner, based on its strong efficacy and benign safety profile. However, with a once-daily dose, should oritavancin receive approval it will be well-positioned in the market.
The advisory committee meeting should allow analysts to revisit those forecasts with a greater degree of certainty.
|Late-stage anti-MRSA antibiotics|
|Annual Sales WW - Sales ($m)|
|Market Status||Product||Pharmacological Class||Company||2008||2009||2010||2011||2012||2013||2014|
|Approved||Zeftera||Cephalosporin||Johnson & Johnson/Basilea Pharmaceutica||2||95||263||437||620||802||984|
|Iclaprim||Dihydrofolate reductase inhibitor||Arpida||-||25||37||65||119||174||228|
|Phase III||PPI-0903||Cephalosporin||Forest Laboratories/Takeda||-||-||11||51||91||128||170|