Login to Your Account



AIDAC supports two new infectious disease weapons

adcom.jpg

By Mari Serebrov
Washington Editor

Citing the need for a bigger arsenal in the war against infectious diseases, the FDA’s Anti-infective Drugs Advisory Committee (AIDAC) unanimously supported approval Monday of two new weapons to treat acute bacterial skin and skin structure infections caused by certain gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA).

The first to get the committee’s endorsement was Cubist Pharmaceutical Inc.’s Sivextro (tedizolid). While the panel voted 14-0 that two phase III noninferiority trials presented sufficient efficacy and safety data for Sivextro, it recommended the FDA require a study specifically in adolescents and teens before the label is extended for pediatric use.

Lexington, Mass.-based Cubist is seeking approval for patients 12 and older, but only a few subjects younger than 18 were included in the trials. The study population also had a limited number of elderly and minority subjects.

Concerned about off-label use because of the convenience of the drug, the panel also wanted to see longer term safety data. The oxazolidinone drug is designed to be administered once a day, either orally or intravenously, for six days, as compared with a twice-daily, 10-day regimen of linezolid (Zyvox, Pfizer Inc.)

The second drug winning the committee’s support was Durata Therapeutics Inc.’s Dalvance (dalbavancin), a second-generation, semisynthetic lipoglycopeptide with a long half-life. Since the drug is administered intravenously once a week for two weeks, it may prove a viable weapon in outpatient use. It was compared with a regimen of vancomycin and linezolid.

In voicing their support for dalbavancin, the committee members recommended postmarket trials in children, pregnant women and minority populations. Several also encouraged the FDA to address concerns about the possibility of liver damage in the labeling. James Steckelberg, a professor in the infectious diseases division at the Mayo Clinic, advised the agency to work closely with Durata to develop follow-up and safety monitoring guidelines since the drug is likely to be used in the outpatient setting.

THE OBJECTIONS

The biggest concerns about the drugs were raised by two speakers during the public hearing sessions. Anna Mazzucco, representing the National Research Center for Women and Families, stressed that neither drug should be approved until more safety studies were completed in minority groups, the elderly and diabetic patients.

Saying that more than 40 percent of antibiotics approved since 1980 have been withdrawn, she added that the risks are too great to allow the drugs on the market while the sponsors are conducting postmarket trials, which could take another 10 years to ferret out additional safety concerns. Mazzucco also questioned whether Sivextro and dalbavancin would actually provide new treatment options for drug-resistant bacteria. She claimed resistance to dalbavancin is similar to that of vancomycin, which has been on the market for years, and Sivextro has cross-resistance with linezolid.

Nida Degesys, national president of the American Medical Student Association, went further with her objections. “Being another option is not good enough . . . unless we know where and in whom those options are an improvement,” she said.

She based her objections on the noninferiority trials used to demonstrate the drugs’ efficacy and safety, claiming that such trials are fundamentally flawed. Several drugs have been approved to treat MRSA, Degesys said, so there’s no need to approve a new drug based on a noninferiority trial.

Countering Degesys’ claims, panelist Thomas Moore, a clinical professor at the University of Kansas School of Medicine, said a noninferiority trial is the only ethical way a new drug can be evaluated in a life-threatening condition for which there are treatment alternatives.

Speaking on behalf of the Infectious Diseases Society of America (IDSA), Amanda Jezek used the public hearing to plead for the development and approval of more antibacterials. While the threat of multidrug-resistant bacteria and the cost of fighting those bugs are growing rapidly, the development of new drugs isn’t keeping pace. As of a year ago, only seven new antibacterials were in development, Jezek said, and only one has been approved since 2010.

Whether the FDA will follow AIDAC’s advice and approve Sivextro and dalbavancin remains to be seen. The PDUFA date for dalbavancin is May 26, and Sivextro’s PDUFA date is June 20. Cubist is seeking similar indications for Sivextro in Canada and the EU.

Cubist (NASDAQ:CBST) added Sivextro to its antibiotics pipeline when it acquired Trius Therapeutics Inc. last year in an $818 million deal. The AIDAC vote gave the company a bit of a boost Monday as it closed at $73.15 – up $3.05. (See BioWorld Today, July 31, 2013.)

Trading for Chicago-based Durata (NASDAQ:DRTX) was halted Monday during the AIDAC meeting.

Dalbavancin has had a rough development road, due in part to a shifting regulatory path.

Pfizer acquired the compound as part of its buyout of Vicuron Pharmaceuticals Inc. in 2005. After receiving three “approvable” letters from the FDA but no approval, it spun out the drug into Durata in 2009.

Durata has big plans for dalbavancin. Using skin infections as the path to the market, the company hopes to develop the drug in osteomyelitis, pneumonia, diabetic foot ulcers and various other conditions. (See BioWorld Today, Sept. 30, 2013.)