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.

Aside from discussion on COVID-19 vaccines, the Advisory Committee on Immunization Practices members Friday also moved to punt a planned vote on universal hepatitis B virus vaccination at birth out to a future date. \n In the second and final day of the Centers for Disease Control and Prevention\'s (CDC’s) Advisory Committee on Immunization Practices (ACIP) September meeting, members of the panel scrapped one vote, reversed another and, in one of four votes on COVID-19 vaccines, stopped just short of an endorsement that had the potential to significantly impede access for many people living in the U.S.Asked whether state and local jurisdictions should require a prescription for individuals to receive a COVID-19 vaccine, the panel was split down the middle, with six “yes” votes and six “nos.” But, because the advisory committee’s chair, Martin Kulldorff, Ph.D., was among those who voted against it, the recommendation did not pass.The outcome followed tense debate over whether the recommended prescription requirement would hinder the availability of COVID shots for Americans, with rifts emerging both between the medical liaison organizations sitting in on the meeting and between the ACIP members themselves. The panel also voted on and passed three other recommendations. The entire committee voted \"yes\" on a proposal to urge the CDC to adjust pediatric and adult COVID-19 vaccine schedules to emphasize “individual-based decision-making,” also known as shared clinical decision-making. In practice, that means discussing the matter with a doctor or other healthcare provider before a vaccination.Under the recommendation, the panel urged that doctor-patient conversations around COVID vaccines for people between the ages of 6 months and 64 years emphasize that the risk-benefit profile is “most favorable for individuals who are at increased risk for severe COVID-19 disease and lowest for individuals who are not at an increased risk.” That language aligns with the restricted FDA approvals granted to Pfizer and Moderna’s updated COVID-19 vaccines last month.The other two votes revolved around encouraging the CDC to provide public communications on certain COVID-19 vaccine “risks and uncertainties” included in an ACIP work group presentation (PDF) and a recommendation that authorized healthcare providers should discuss the risks of vaccination with individual patients.The first issue passed with 11 \"yes\" votes and a single \"no,” while the second was backed unanimously by all 12 ACIP members. The vote on a prescription requirement for COVID vaccines undoubtedly posed the greatest threat of disruption to current U.S. vaccine policy, though the ACIP members butted heads over exactly what the access implications of their decision would be.“We’re not currently authorized as providers in [Medicare] Part B language, and so we can’t currently write a prescription,” ACIP panelist Hillary Blackburn, director of medication access and affordability at specialty pharmacy Ascension Rx, said ahead of the vote. “In some states … it would be a barrier for access if a prescription is required.”Blackburn brought up the issue in an effort to amend the language in the voting question, but, as several of her ACIP peers suggested she may simply want to vote “no” on the recommendation, the issue was moved to a debate. The move marked a continuing theme of uncertainty among the panelists—both Thursday and Friday—about the weight their votes carried and the consequences of the voting question language.Catherine Stein, Ph.D., a professor in the department of population and quantitative health at Case Western Reserve University—who was added to the committee just this week—echoed Blackburn’s concerns.“I am all about informed consent, and I think given the earlier discussions about risks and benefits … that discussion is really important,” she said. “But I’m really concerned about the requirement of a prescription, because I believe the segment of the population that is underinsured has lack of access to healthcare—they’re going to be unable to get a prescription, and those are the people that are at highest risk for a lot of these comorbid conditions.”Aside from safety data presented by the CDC at the ACIP’s request, panel member Retsef Levi, Ph.D.—a professor of operations management at the MIT Sloan School of Management—offered a separate work group presentation outlining efficacy concerns as well as apprehensions around safety signals such as myocarditis.Other panelists, like pediatrics professor and former pediatrician Cody Meissner, M.D., and Joseph Hibbeln, M.D., former chief of the section on nutritional neurosciences at the National Institutes of Health, also expressed significant misgivings about impeding access with a COVID shot prescription requirement.But Levi dissented, arguing that he believed the vote was about “leaving this to every state to figure it out, and the state can decide if it’s going to indeed limit access.”He then pressed harder on the question of access: “So we are saying that people that don’t have access to medical—so how would they get antibiotics? Why? Based on that logic, we would need to also allow taking over-the-counter antibiotics and other prescription drugs. Why would we do that? We don’t do that because we believe that the prescription of these interventions requires some nuanced assessment of the medical condition of the person to actually decide whether it’s appropriate or help them decide whether it’s appropriate for them to take.”But Meissner came back swiftly against that line of thinking, noting that he was “a little uncomfortable” with the comparison between antibiotics and vaccines, since one is given to a sick person and the other is generally intended to help protect healthy people.“If we require a prescription, you know we’re going to increase healthcare costs,” he added. “And I don’t think this is a reasonable basis to do that.” Aside from the discussion on COVID-19 vaccines, the ACIP members on Friday moved to punt a planned vote on universal hepatitis B virus (HBV) vaccination at birth out to a future date. After concluding discussion on the matter Thursday, ACIP members started to revive talks on the HBV universal birth vaccine—with one member attempting to bring in new data she’d reviewed the previous evening. Deliberations quickly broke down, with the panelists ultimately voting to table the decision.Separately, the ACIP members reversed their vote on a recommendation they’d shot down Thursday pertaining to coverage of Merck’s combination measles, mumps, rubella and varicella (MMRV) vaccine under the U.S.’s Vaccines For Kids (VFC) coverage program.The original vote to maintain VFC coverage on Thursday conflicted with the panelists’ decision to urge against recommending the MMRV shot as the first dose in a two-vaccine MMRV immunization sequence.Kulldorff gave his take on the situation at the top of Friday’s meeting, noting, “There is one thing, though, in which we are rookies, and with one exception, this was either our first ACIP meeting or second, and there are many technical issues that we might not grasp as of yet.” The “exception” Kulldorff referred to was Meissner, who is the only current ACIP member to have served on the committee previously.Back in June, Department of Health and Human Services Secretary Robert F. Kennedy Jr. ousted the entire sitting ACIP committee, citing issues with conflicts of interest, before quickly slotting in his own appointees.As the meeting wrapped up Friday, confidence in the ACIP among the broader medical community looked to be on incredibly shaky ground.Friday, 75 health organizations—including the American Association of Nurse Practitioners, the American Pharmacists Association, the American Public Health Association, the National Association of Pediatric Nurse Practitioners and many others—sent a letter (PDF) to the ACIP calling on the vaccine panel to truly uphold gold-standard science, vote to recommend full vaccine schedules that ensure access and patient choice, and recommend COVID-19 vaccines for all people in the U.S. ages 6 months and older.Many of those medical associations previously participated in ACIP work groups that helped the panel draft its voting questions. However, they were iced out of the process in early August.Representatives from those liaison groups were allowed to speak during Friday’s meeting, but their time was limited, and it seemed apparent they didn’t feel their voices were being heard.\"You want debate and discussion, but you\'re muting people and silencing them,\" the American College of Physicians’ Jonathan Goldman, M.D., said at one point after repeated attempts to mute his mic.  Meanwhile, the American Medical Association noted in a Friday statement that the ACIP\'s new processes and recommendations \"leave parents confused about how best to protect their kids and unable to choose the combined MMRV vaccine for children under 4 years old.\"The organization continued that it\'s \"concerned that this change not only reduces parental choice, but also reflects ACIP’s reliance on selective data in forming its guidance.\"