MERCK’s PedvaxHIB PROPOSED "DEAR DOCTOR" LETTER ON LOW IMMUNOGENICITY RECOMMENDS ADDITIONAL DOSE FOR CHILDREN; NO INCREASE IN HAEMOPHILUS B SEEN

Merck has drafted a "Dear Doctor" letter recommending that physicians give an additional dose of PedvaxHIB to children who received doses from lots of the Haemophilus b vaccine that had low seroconversion rates. Speaking at the Oct. 28 meeting of FDA's Vaccines and Related Biological Products Advisory Committee, Merck Director of Clinical Research, Paul Mendelman, MD, said, "Merck has prepared this letter to physicians which recommends an additional dose of PedvaxHIB for any infant or child who received at least one dose of the lot in question." FDA currently is reviewing the letter. Mendelman and other Merck representatives presented the advisory committee with an update on the company's efforts to follow up on the problem of some lots of PedvaxHIB that did not produce the level of antibodies considered protective in some children who received the vaccine. Children who did not initially produce the expected antibody level seroconverted after getting boosters. The immunogenicity problem was discovered when the National Institutes of Health notified Merck on June 12 that one lot of PedvaxHIB used in a Haemophilus b vaccine mix-and-match study showed reduced immunogenicity, Mendelman explained. Merck subsequently notified FDA ("The Pink Sheet" July 20, T&G-12). Merck Biological Quality Control Senior Director Wayne Morges, PhD, noted that the additional dose of PedvaxHIB recommended in the "Dear Doctor" letter should be given to children previously immunized with doses from problem lots of the vaccine "to be assured of continuing protection." If okayed by FDA, the "Dear Doctor" letter may be distributed to all pediatricians or just to the few thousand physicians known to have received vaccine from the questionable lots, Merck said. Merck Vaccine Division Marketing Senior Director Gary Zieziula noted that "through our branch distribution system, we can track approximately 99% of the doses to the end physician." He added that Merck will contact those physicians at the time the letter goes out. The letter will contain an 800 number for doctors to call if they are not contacted by Merck by a certain date. Mendelman said that Merck will provide doctors with replacement supplies of vaccine, "credit toward future vaccine purchases or cash payment." Merck has been monitoring children who may have received vaccine doses from the suspect lots during postmarketing studies. Mendelman said "a total of 14 cases [of Haemophilus b] after PedvaxHIB" have been reported. Of these 14 children, seven got doses from the lots in question and seven did not get doses from the suspect lots, he pointed out. "Disease surveillance shows no apparent increase for children who received lots in question and active surveillance is ongoing," he stated. Since learning of the immunogenicity problem, Merck has been conducting numerous tests not routinely conducted on its vaccine lots to determine the scope and source of the problem. Mendelman noted that "in August, based on intensive investigation...an analytical test was observed that suggested a reason for the difference in the immunogenicity in that the lots in question appeared to have a particular ratio of a unique amino acid to PRP that was different compared to lots that performed well in the clinic." Although Merck does not know if this biological marker is the cause of the low immunogenicity, the marker has helped identify the questionable vaccine lots, the company said. FDA Division Bacterial Products Director Bascom Anthony, MD, told the committee that, acting on Merck's data, "we have modified the lot release criteria for this vaccine and have a marker, which we hope is an indicator that this problem is not likely to occur with future lots."