Welcome to your digest of approaching regulatory and clinical readouts. Mannkind must be hoping that it will not be made a fool of on April 1 when an FDA panel discusses its inhalable insulin Afrezza. But, given serious questions over its approvability, less than impressive clinical results and delivery route, that could be asking for too much.
Next week will hold the FDA’s anti-infective drugs panel, due to meet on March 31 to discuss two antibiotics to treat acute bacterial skin and skin structure infections, tedizolid and dalbavancin. The drugs' developers, Cubist and Durata, will point to the urgent need for new antibiotics in seeking regulatory backing.
Both tedizolid and dalbavancin are seeking approval for treating acute bacterial skin and skin structure infections (ABSSSI) caused by Gram-positive microorganisms including MRSA.
Tedizolid is a second-generation oxazolidinone antibiotic, an improved version of Pfizer’s blockbuster Zyvox, which goes off patent next year. Its filing was based on the results of the Establish-1 and Establish-2 studies.
The trials tested once-daily oral and intravenous formations (TR-701 IV) of the project and showed non-inferiority to twice-daily Zyvox. Tedizolid was viewed as more potent and safer, with more convenient dosing (For Trius the hard work is just beginning as filing looms, March 26, 2013).
Its sales are expected to reach $202m by 2018, according to consensus data from EvaluatePharma. Meanwhile, Zyvox revenue is set to drop from $1.4bn this year to $318m in 2018. Since it will take time to get tedizolid into the hospital formularies it will need to make the most of its window of opportunity and bank fast sales before the entry of Zyvox generics. The PDUFA date is June 20.
The second antibiotic to come under scrutiny will be Durata’s lone pipeline project, dalbavancin. It is intravenous and belongs to the same class as vancomycin, a widely used antibiotic used to treat MRSA.
Dalbavancin was acquired by Pfizer through its takeover of Vicuron Pharmaceuticals for $1.9bn in 2005. However, development was marred by mixed clinical success, with the FDA issuing three approvable letters. In 2008 the marketing applications were withdrawn by Pfizer, which planned to start an additional trial. Durata acquired rights in 2009 and conducted two phase III studies.
The Discover-1 and Discover-2 trials compared once-weekly dalbavancin against twice-daily vancomycin, with the option to switch to oral linezolid. In Discover-1 the clinical response at 48-72 hours was 83% for dalbavancin versus 82% for vancomycin/linezolid. In the second trial it was 77% versus 78%. The PDUFA date is May 26.
Sales in 2018 are expected to reach $268m, according to EvaluatePharma, with analysts expecting a partnering deal outside of the US. Last November, Durata signed a credit agreement with PDL BioPharma, which is providing up to $70m in debt financing.
Dalbavancin will also have to deal with Zyvox generics, while competition is also expected from The Medicine Company’s oritavancin, which is similar to vancomycin. Oritavancin’s US approval is set for August.
With the rise of resistance the need for new antibiotics is high. But, while the FDA panel might be more inclined to endorse these new antibacterials, the market potential still remains questionable.
After years of clinical development and several regulatory setbacks, Mannkind’s Afrezza faces an FDA panel on April 1 in what must surely be its last chance at reaching the market.
Last year, the company said phase III trials of Afrezza in type 1 and 2 diabetes met their primary endpoints, but only just, and uncertainties were raised over changes in patients' body weights (Short-lived party for MannKind as Afrezza scrapes through phase III, August 15, 2013).
Afrezza previously received two complete response letters and its approvability is still under a large question mark as the FDA is known to be doubtful of products delivered into the lungs.
Sales are forecast to reach $621m by 2018, according to consensus from EvaluatePharma, though tellingly no partnership has yet materialised for Mannkind. The diabetes market has also moved on to pen-style insulin injectors, reducing the need for alternatives and adding to the already serious doubts over Afrezza’s potential.
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