Merck's Pneumococcal Vaccine Market Expansion Stalled By Ever-Changing, Crowded Field

The risks of shifting a crowded and rapidly changing adult vaccine market were on display in late June as Merck & Co., Inc. failed to garner a US Centers for Disease Control and Prevention advisory committee vote on recommending its new pneumococcal vaccine for all US adults 50-64.

The US Food and Drug Administration approved Merck’s Capvaxive (pneumococcal 21-valent conjugate vaccine) 17 June for those 18 and older. (Also see "US FDA Vaccine Approvals Set Up CDC Votes On Merck’s Capvaxive, Moderna’s mResvia" - Pink Sheet, 19 June, 2024.)

The company was hoping for a CDC Advisory Committee on Immunization Practices (ACIP) recommendation for routine vaccination in adults 50 and older, which would have given it an edge over Pfizer Inc.’s Prevnar 20 (PCV20). (Also see "Merck’s Newly Approved Capvaxive Could Have Edge Over Prevnar 20 In Adults" - Scrip, 18 June, 2024.)

Instead, the ACIP left the two vaccines on even footing for now.

The committee recommended PCV21 for US adults age 19 and older who currently are recommended to receive a pneumococcal vaccine, meaning the vaccine could only be used in adults under 65 if the person has a risk-based indication for PCV.

Concerns about cost-effectiveness and the vaccine’s unknown duration of protection, which was described as further complicating what was described as the most complex adult vaccination recommendation currently in place, led the committee to push a vote on the topic to a later date.

While some ACIP members seemed eager to give Merck the universal go-ahead in the 50 and older group to address health equity concerns, the committee ultimately decided it wanted data looking at the impact of using the other approved PCV vaccines in all adults 50 and older before making a decision.

But, the longer the ACIP waits to make the decision, the more complex it could become. GSK plc and Vaxcyte, Inc are working on late-stage trials of PCV vaccines that cover additional serotypes. (Also see "Change Is Constant For Pneumococcal Vaccines: US CDC Prepares For Merck’s V116" - Pink Sheet, 17 April, 2024.)

“Our vaccination policy recommendations generally tend to … settle over time because we gather more knowledge,” said Matthew Daley, senior investigator at the Institute for Health Research, Kaiser Permanente Colorado. “Is that true here, too? I don't know, because the landscape keeps changing because of the new vaccines.”

There are four recommended adult pneumococcal vaccines, though Pfizer currently dominates the market with PCV20. The other vaccines are PCV15 and PPSV23, which as a polysaccharide vaccine is the only non-conjugate vaccine of the bunch. Current CDC recommendations also must incorporate adults who received older vaccines like PCV13 and PCV7.

Reluctance to Single Out One Vaccine

ACIP members acknowledged that Merck’s PCV21 is not simply Pfizer’s vaccine with an additional serotype. Capvaxive includes eight unique serotypes that are not covered by Prevnar 20 and can address the serotypes responsible for about 84% of invasive pneumococcal disease in adults 50 and older, versus 52% for Prevnar 20.

Despite the differences, Daley said he was uncomfortable recommending just one of the PCV vaccines for everyone 50 and older while leaving the other vaccines with a risk-based recommendation in those 50-64.

“It would just be too hard to implement,” he said.

It “would be really confusing to say if you don’t have a risk factor [at 50] get 21, but if you do have a risk factor you can get 21 or 20, or 15 plus 23.” added Jamie Loehr, owner of Cayuga Family Medicine.

An additional complicating factor is that Pfizer’s PCV20 and the other PCV vaccines besides Merck’s PCV21 cover serotype four. That serotype was once thought to be nearly eliminated in the US, but has been reemerging in recent years, particularly in Alaska and Alaska Natives and homeless adults.

Daley said the committee should consider a universal recommendation down to age 50 for all high valency PCV vaccines, not just the Merck product.

But Status Quo Leaves Stark Inequities

Still, Daley and others were concerned about the health equity gap for black Americans that likely will remain without changing course. Black Americans have higher rates of disease that peak earlier, between ages 55-59.

“I appreciate the workgroup says we really shouldn’t decide [about 50-64] today but we need to decide at some point and I hope we get there pretty soon, in part because of the racial and ethnic disparities in invasive disease,” he said.

“It is striking to me that there is this disparity which we actually already knew among the black patients from 50 to 64, their health profiles are equivalent to the 65-year-old,” said Oliver Brooks, Chief Medical Officer at Watts Healthcare Corporation. “So I believe that it would be very helpful to that community to have a universal recommendation.”

Most ACIP members felt that an age-based recommendation would be easier to implement and lead to better uptake than at present in the under 65 population, including among people who are eligible under the risked-based recommendation, but do not get the shot.

While the majority of adults subject to the current universal age-based recommendation are vaccinated, 65.8% of adults 65 and over, the percentage drops to 22.2% for those age 19-64 who are covered by the risk-based indication.

Durability Gap Makes Decision Harder

Some committee members worried about the costs of vaccinating everyone at age 50, particularly since it is unclear whether people might need additional doses later in life.

Integrating PCV21 into the current schedule recommendations is likely to be cost-saving to $58,000 per quality adjusted life year (QALY) gained, models presented to the ACIP indicated.

But giving PCV21 to everyone age 50-64 was modeled at $3,000 to $270,000 per QALY gained. Giving PCV20 to everyone in that age group was modeled as being more costly at about $37,000 to $630,000 per QALY gained.

Questions about the length of the vaccine's protection made the committee’s decision more challenging.

“We don’t know if the protection lasts for 15 years or it lasts for longer,” said Loehr. “If it lasts for 30 years years that would change the model completely and this might be a much less expensive vaccine.”

But ACIP Chair Helen Keipp Talbot, a professor of medicine at Vanderbilt University, questioned some of the model assumptions and cost-effectiveness estimates. She said the assumptions on length of protection were based on the polysaccharide vaccine, a T-cell independent vaccine, whose protection declines significantly in five years.

PCV21 “is a conjugate vaccine, so the life of this vaccine, the impact that this vaccine should have, should be much, much longer than the polysaccharide vaccine,” Talbot argued. “Additionally, giving the vaccine at 50 may actually give the vaccine before people begin having immune senescence, theoretically, except for the people who are already at high risk. So, you actually might provide better protection for them at 70, if you vaccinate them at 50 then if you vaccinate them at 65.”

Simplify For Success

Talbot suggested the PCV space could benefit from fewer vaccine options, and particularly stressed her desire to no longer use the polysaccharide vaccine, Merck’s Pneumovax 23.

“I'd like to point out the children have gone from PCV7 to PCV10 to PCV13. And it's been no big deal,” Talbot said. “Because we’ve gotten rid of the prior vaccine each time. For adults, we’re hanging on to polysaccharide for our dear life.”

“So I think one of the things we need to think about for adults is we need to be as simplistic as we are for the children and not wait for perfection or have 1,000 options,” she added. “The childhood immunization schedule has been much more successful. But once again, its age based, and it's one vaccine. And so that is something to think about.”

But Sarah Long, professor of pediatrics at Drexel University College of Medicine, worried about making a preferential recommendation since there is no clinical effectiveness data on PCV20 or PCV21 and PCV21’s lack of coverage of serotype four. 

The CDC's Melinda Wharton recently said preferential recommendations carry a high bar. (Also see "The Future of ACIP: CDC Vaccine Policy Lead Looks Beyond COVID" - Pink Sheet, 6 May, 2024.)

Meanwhile other ACIP members tried to place a possible expanded PCV recommendation in the context of a growing adult vaccine schedule and wondered whether it could backfire for all vaccines. (Also see "Mismatch Between Growing Vaccine Pipeline and CDC’s ACIP Capacity" - Pink Sheet, 26 April, 2024.)

With more adult vaccines coming on the market, like those for RSV, Camille Kotton worried about issuing an age-based recommendation for younger adults, overwhelming them with more shots than they may really need, and creating more vaccine hesitancy. (Also see "Revising Adult RSV Policy: US CDC Moves Toward Risk-Based Vaccine Recommendation" - Pink Sheet, 27 June, 2024.)

“I am concerned about potential collateral damage on other vaccines,” Kotton said. “And already I've heard from so many providers that they are overwhelmed by the number of choices and changes. Some people are saying that they don't want to get RSV vaccine or other vaccines because they feel like they've just had enough vaccines and they're are a pin cushion.”

“I have to say I'm not so thrilled myself to go out and get a vaccine of unclear need and if I'm quite pro-vaccine I do worry it’ll have a collateral impact in potentially a negative way on other vaccine issues,” she added. “I would rather focus the efforts on perhaps vaccines for which there might be more benefit.”