ATLANTA — The Centers for Disease Control and Prevention's vaccine advisory panel voted to drop the recommended number of postexposure doses of rabies vaccine from five to four, based on data suggesting that doing so would not adversely affect outcomes for exposed individuals.
The decision of the Advisory Committee on Immunization Practices stems from the “tenuous” nature of the rabies vaccine supply since 2007. The rabies vaccine made by Novartis (RabAvert) is now available for both pre-exposure and postexposure immunization without limitations. Sanofi Pasteur's rabies vaccine (Imovax) is still available only for postexposure prophylaxis, the CDC's Charles Rupprecht, V.M.D., said at ACIP's June meeting.
An interim four-dose schedule was developed to address the supply problem, and now the committee has advised the four-dose schedule for routine use, based on data from both animal and human clinical trials suggesting that recipients develop detectable rabies virus neutralizing antibodies by day 14, when a vaccine schedule of doses given at days 0, 3, 7, and 14 is used. (The fifth dose is given at 28 days.)
In addition, no significant differences were documented between the four- and five-dose rabies vaccine schedule in the relative amount of neutralizing antibodies produced. Equivalent outcomes were observed in comparison studies using four doses of vaccine given along with rabies immune globulin, said Dr. Rupprecht, chief of the CDC's rabies program.
Nonetheless, if ACIP's vote is approved by the CDC, it presents a conflict with the labeling approved by the Food and Drug Administration, which still recommends five doses of rabies vaccine. Any change to the labeling would require a request from the manufacturers and submission by them of additional data to support the change, FDA representative Dr. Norman Baylor said, adding that only in the event of a safety concern would the FDA be able to force such a change.
Spokesmen for Novartis and Sanofi Pasteur do not support the change. “It's what the committee feels is best based on the data available to them, but we can't talk about off-label use, and our label firmly states it's a five-dose regimen,” Sanofi Pasteur's Philip Hosbach said in an interview at the meeting.
Mr. Hosbach, vice president of immunization policy and government relations at Sanofi Pasteur, added that his company's supply issue stemmed from a planned shutdown of its manufacturing plant in 2007 for an upgrade. It is set to resume operation in the fourth quarter of 2009 with a full supply.
Clement Lewin, Ph.D., head of strategic immunization planning at Novartis Vaccines and Diagnostics, also reacted negatively to the ACIP vote. “It does mean a challenge for Novartis because the FDA guidance clearly states five doses and Novartis doesn't support off-label use of any of its products.”
He added, “We're currently supplying [rabies vaccine] for both pre- and postexposure prophylaxis. … Anyone who needs vaccine pre- or postexposure is able to get it. Last year the supply constraints were such that use was restricted to postexposure. Currently we are meeting all the demand of the United States. There is no supply issue at the moment,” Dr. Lewin said in an on-site interview.