MMR-varicella zoster virus vaccine(GlaxoSmithKline Plc)

iStock, Visual Generation While last week’s recommended changes by CDC advisors to the MMRV vaccine schedule are unlikely to have a tangible effect on Merck’s business, the company said the removal of choice for healthcare providers is “concerning.” Merck is the maker of the measles, mumps, rubella and varicella vaccine that has come under scrutiny from a CDC committee with members installed by Health Secretary Robert F. Kennedy Jr. The Advisory Committee on Immunization Practices (ACIP) last week voted to recommend a change to the MMRV vaccine schedule restricting the four-way combination shot to children four and up. The committee recommended that children under that age receive the MMR and varicella (chickenpox) vaccines separately. Previously, the committee recommended that children receive two doses of the combo MMRV vaccine—one at 12-15 months and another between age 4 and 6. Alternatively, the MMR and chickenpox vaccine could be administered separately, “preferably at the same visit.” There’s only one four-way MMRV vaccine authorized in the U.S.: Merck’s ProQuad, which was approved in September 2005 for children aged 12 months through 12 years of age. The vaccine combined two of Merck’s previously approved shots, M-M-R II and Varivax, into one, allowing for a single administration. Last Thursday’s ACIP discussion revolved around a rare risk associated with the MMRV vaccine called febrile seizures, which can occur with an instance of high fever. The CDC said that use of the combo shot resulted in about one extra febrile seizure for every 2,300-2,600 doses of the quad vaccine administered, as compared to the separate MMR vaccine plus the varicella vaccine. The ProQuad label includes a warning of this risk, and additional studies have been done since the vaccine’s approval to add more data to the case supporting its benefits. Merck, in a statement emailed to BioSpace , called the removal of choice for healthcare providers “concerning.” “The recent ACIP vote regarding the MMRV vaccine and the discussion around hepatitis B vaccination occurred in the absence of new scientific data—in contrast to the historical practice of new data driving any discussions for changes to the recommendations pertaining to immunization schedules,” the company wrote. The label for ProQuad has been updated numerous times over the 20 years since its approval as new evidence became available, according to FDA records . The actual financial impact on Merck should be minimal. The company reports revenue for ProQuad along with the triple M-M-R-II shot and Varivax together. Combined, they achieved sales of $609 million. Without the quad MMRV shot, the triple MMR plus Varivax can be used together. “We urge ACIP to reinstate liaison organizations and clinicians with frontline experience to its work groups,” Merck said in its statement. “Their participation is essential to preserve transparency, ensure robust, clinically grounded deliberation and safeguard scientific integrity.” Merck also defended its vaccine lineup in a letter sent to the ACIP committee ahead of the hearing. The History of ProQuad Merck’s ProQuad application was based on five clinical trials that were conducted in the U.S., with more than 6,200 children receiving a dose of the combo vaccine. In total, over 1,400 kids received two doses over the course of the trials. The shot had efficacy ranging from 91% for varicella up to 98% for mumps. Safety was analyzed using data from nearly 4,500 children aged 12 to 23 months who received ProQuad. This was compared to safety data from Merck’s individual MMRII and Varivax vaccines. In the ProQuad group, 81% of the children reported some sort of adverse event; 31% reported injection site reactions such as rash or redness. The ProQuad group had a higher rate of fever compared to the MMRI + Varivax group, with 37% reporting this side effect. As for more severe adverse events, the rate of high fever—which can result in febrile seizures—was 0.2% for the ProQuad group and 0.4% for the other group. Adverse events decreased for the children who had a second dose of ProQuad. ProQuad was approved in September 2005; Merck agreed to conduct a post-marketing study of 25,000 subjects to evaluate the risk of febrile seizures. The company also did more post-approval testing of a second dose in children aged 15 to 23 months, which was added to the label in February 2008 . The approval has been updated several times over the years to include additional routes of administration. The label has also been updated as more safety information became available. Most recently, the FDA approved an addition in November 2024 to acknowledge a case of congenital rubella syndrome that occurred after a pregnant woman was inadvertently vaccinated with an MMR vaccine from an unknown manufacturer. The other leading manufacturer is GSK, which markets the MMR vaccine Priorix. The shot has been used globally for decades for the three-way vaccination but was not approved in the U.S. until 2022. A four-way shot that adds varicella to the mix, called Priorix Tetra, has not been approved in the U.S. but is marketed elsewhere in the world. GSK’s third vaccine, Varilrix, covers varicella and is not available in the U.S. GSK reports sales of the MMRV shots together. U.S. sales for the vaccines were $13 million for the second quarter, representing 37% growth. Prior to the availability of these vaccines, all these diseases were common in childhood, the FDA wrote in Merck’s ProQuad regulatory review , dated August 2004. Typically, the infections are minor, but all can result in serious complications. Measles can cause pneumonia and encephalitis, or swelling of the brain. Mumps can cause aseptic meningitis, deafness and swelling of the testicles. Rubella infection in pregnant women can cause congenital rubella syndrome in infants, which can produce severe birth defects including deafness and heart problems. Varicella can also lead to pneumonia and brain swelling, as well as bacterial superinfection and Reye’s syndrome, a serious condition that causes swelling in the liver and brain. Vaccines for MMR were introduced beginning in 1963, reducing instances of infections by 99%, according to the FDA regulatory document. Varicella vaccines followed in 1995 with the approval of Varivax, but rates did not fall as precipitously. The FDA attributed this to the separate shot. Therefore, the FDA explained in Merck’s ProQuad approval docs that approving the four-way shot could increase varicella vaccination rates and decrease the disease in the U.S., as well as reduce the number of injections required. “Vaccines and immunizations are our best defense against many serious and potentially life-threatening diseases, and the scientific evidence supporting their use is clear,” Merck said in its statement. “They are the cornerstones of pediatric preventive care and public health, and we remain committed to rigorous scientific dialogue, transparent sharing of data and gold-standard statistical and clinical trial methodologies.” Merck also commended ACIP for deferring a vote on the hepatitis B dose at birth. The committee heard that this shot has led to a 99% decline in reported cases of acute hepatitis B in children under 19 in the U.S. over the past 30 years. “This is a remarkable achievement and removing the birth dose recommendation risks a resurgence of chronic hepatitis B infection, liver damage, cirrhosis, liver cancer and even death,” Merck said in its statement. The company markets Recombivax HB for all age groups.