Peter Wehrwein

One of the many questions hovering over Paxlovid (ritonavir-boosted nirmatrelvir) is how much of a difference the antiviral treatment medication makes in people who have been vaccinated against COVID-19. The clinical trials that led to the FDA authorizing the medication that showed Paxlovid had a large effect on COVID-19 severity did not include people who were vaccinated.

The question hasn’t been fully answered but some evidence is coming in.

 about interim results from its EPIC-SR trial of Paxlovid that mentioned a sub-group analysis of 721 vaccinated adults with at least one risk factor for severe COVID-19. The press release said that Paxlovid led to a 57% reduction in hospitalization or death in that vaccinated group, although the difference didn’t meet the statistical standards for showing a real difference.

More recently, the research arm of Epic, the electronic health record company headquartered in Verona, Wisconsin, shared 

 showing large differences in hospitalizations and deaths between those treated with Paxlovid and those who hadn’t been treated with Paxlovid among people who had been vaccinated. The differences were larger among those 65 and older. But the Epic research also showed a difference in the 50-64 age group.

For example, there 27 hospitalizations (0.13%) and zero deaths among 20,407 peoplein that age who were treated with Paxlovid and who had been fully vaccinated and had had a booster. Among the 38,689 adults in the fully vaccinated, boosted group who were not treated with Paxlovid there were 143 hospitalizations (0.37%) and seven deaths (.02%). That works out to a hospitalization rate that is almost three times higher among those not treated with Paxlovid compared with those that were.

Jacqueline Gerhart, vice president of informatics at Epic, noted that research findings from Israel had suggested that Paxlovid didn’t make a difference in the 50-64 age group. But that was a smaller study than the one conducted by her and her colleagues that might not have the statistical power to detect a difference. The size of Epic’s database, called Cosmos, is an advantage.

“On first look at these numbers, we not only saw a difference, but it was statistically significant, meaning that the confidence intervals didn't overlap, meaning that we could be very confident that there actually benefit to taking Paxlovid between age 50 and 64,” Gerhart said in an interview.

Gerhart also looked at the hospitalization and mortality benefits of Paxlovid among those who were vaccinated but not boosted and those were vaccinated and double boosted. The results showing Paxlovid as protective against hospitalization and death were similar. The Epic researchers did not, though, break out Paxlovid results for people who are not vaccinated.

“We weren’t trying to say how much better protected you are being vaccinated and taking Paxlovid. We were trying to say, if you have already been vaccinated, is there still benefit to taking Paxlovid. And the answer is yes,” said Caleb Cox, an Epic Research lead.

Paxlovid has become the dominant form of treatment for COVID-19 in the United. According to a tally by HHS, 5.2 million doses have been administered between the Dec. 7, 2021,and Oct. 9, 2022.

This story originally appeared in Managed Healthcare Executive.

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Findings by researchers at Epic, the electronic health record company, show that the benefits extend to people ages 50-64.

Paxlovid Has Hospitalization, Mortality Benefits Among the Vaccinated

 (elexacaftor/ivacaftor/tezacaftor) was approved by the FDA in 2019, evidence from clinical trials suggested that oral drug might be a major advance in treatment for people with cystic fibrosis with the most common mutation that causes the disease, sparing them hospitalizations and the “pulmonary exacerbations” of worsening cystic fibrosis, which include severe coughing, shortness of breath and increased risk of infection.

Findings from a real-world evidence analysis by 

 of 412 people with cystic fibrosis who started taking Trikafta show that those hopes were justified.

But they also raise issues about costs, which tripled.

The research, published in a poster presented this week at the AMCP Nexus 2022 meeting in National Harbor, Maryland, shows that after starting Trikafta, the people with cystic fibrosis had markedly fewer in-patient hospitalizations during the six months after they started taking the drug than during the six months before they started taking it (199 before vs. 58 after, a 71% decrease). The same was true for pulmonary exacerbations (675 before vs. 319 after a 53% decrease) and visits to the emergency department (126 before vs. 70 after, a 44% decrease).

The findings from Prime, a pharmacy benefits management (PBM) company owned by Blues plans, also show some steep cost savings from the fewer hospitalizations and emergency department translated.

Using its claims data, a Prime research team led by Landon Marshall, Ph.D., principal health outcomes researcher, found that average medical costs of the people taking Trikafta decreased from $31,345 during the six months before they started taking the drug to $11,260 during the six months after they started taking it, which works out to a 64% decrease. On a per utilizer per month basis, that is $5,224 before Trikafta and $1,877 afterward.

But the cost picture is incomplete without the cost of Trikafta factored in, and it flips once it is, according to Prime’s research. Using Prime’s pharmacy benefit claims, Marshall and his colleagues found that the average pharmacy benefits costs jumped from $33,804 in the six months before people starting Trikafta to $187,359 afterward, a 454% increase. On a per utilizer per month, the jump was $5,634 before the drug to $31,227 after.

Once the medical benefit savings are combined pharmacy benefit increases into all-cost figure, Prime’s math shows that the medical savings are more than offset by the cost of Trikafta. In fact, the Prime analysis shows that the average all-cost figure for the 412 patients in the study tripled from $65,149 in the six months prior to the start of Trikafta therapy to $187,359 in the six months afterward. On a per utilizer per month basis, that works out to $10,858 before Trikafta to $33,103 during the first six months of taking the drug.

“We noticed, consistent with the clinical trial evidence, we do see the benefit (of Trikafta) in the real world. But what we also see in the real world that the clinical trial doesn’t show you is anotable shift in cost,” Marshall said in a brief interview at the AMCP Nexus meeting.

Marshall said Prime plans on continuing to follow the cystic fibrosis patients and that longer term research may provide information about the durability of Trikafta’s clinical benefits and adherence.

Prime’s real-world findings are consistent with the 2020 

 of Trikafta by the Institute for Clinical and Economic Review (ICER), the cost-effectiveness organization. ICER gave Trikafta gave an A rating for evidence of clinical benefit but said its cost-effectiveness analysis showed the drug should be priced at between $67,900 and $85,500 per year.

A real-world study by the PBM shows major benefits from the new cystic fibrosis drug when it comes to hospitalizations and pulmonary exacerbations. But total cost of care of patients tripled because the drug is expensive.

 Trikafta Effective But Costly, Says Prime Therapeutics

 to restrict Medicare coverage of Aduhelm (aducanumab) to people enrolled in approved clinical trials would likely lead to fewer Alzheimer’s patients taking the drug and reduced Medicare expenditures.

Even so, the cost burden of Aduhelm worries payers. The discussion of the drug's cost has been almost exclusively on the price of the drug itself, which Biogen slashed in half late last year, from $56,000 to $28,200, in a bid to make the drug more palatable to payers. In November 2021, before Biogen announced the price cut, CMS announced a 14.5% increase in 2022 Medicare Part B premiums that was attributed, in part, to the added cost of covering Aduhelm.

., of UCLA argue in a research published in 

 yesterday that Aduhelm will result in spending on PET and MRI scans and other “ancillary” services beyond the cost of the drug itself. In their calculations, the cost of those ancillary services would  comprise 20% of the total estimated Medicare Part B spending associated with Aduhelm.

Prior to the CMS proposal that might restrict coverage to those enrolled in sanctioned clinical trials, Mafi and his colleagues calculated that 1.1 million people might be eligible for Part B coverage of Aduhelm in a “lower bound” estimate that assumes prescribers would stick to the criteria used in clinical trial. Their “upper bound” estimate of eligibility was 5.7 million people.  

Based on those estimates and a projection that just 25% of those eligible would receive Aduhelm, the researchers estimated that Medicare spending on Aduhelm could range from $7 billion per year, $1.4 billion of which would be for ancillary services, up to $37.4 billion, $7.5 billion would be for ancillary services.

Some of the ancillary services included in these calculations are PET scans ($2,300 per year per patient on average, counting  patient coinsurance), routine MRIs ($555), APO E serum testing ($100 per patient), and hospitalization for adverse events ($294). 

One of the important predicates for these calculations is that a large percentage (41% of those on the highest dose) of the patients in the pivotal clinical trials of Aduhelm developed 

 (ARIA) that are characterized by fluid retention and microhemorrhages in the brain. The ARIAs weren’t necessarily serious or symptomatic, but they would likely to mean additional MRI scans and visits with neurologists and, therefore, added expense.

In a research letter published in JAMA Health Forum, researchers say most of the cost figures for Aduhelm have left out the additional MRI scans and other services that will be required because the drug is associated with the development of amyloid-related imaging abnormalities (ARIAs).

Researchers: Ancillary Services Would Comprise 20% of Medicare Spending on Aduhelm

A final evidence report is scheduled to come out on Aug. 15

When the FDA approved Biogen’s controversial Alzheimer’s drug, Aduhelm (aducanumab), in June 2021, the Institute for Clinical and Economic Review (ICER) joined the chorus of criticism.

 that said that the FDA “has failed in its responsibility to protect patients and families from unproven treatments with known harms.” Two months later, ICER came out with a pricing report that said the drug should be priced between $2,500 and $8,300 per year, which was far below the initial price of about $56,000 a year. Biogen announced in December that it was halving the price.


This year, ICER has Aduhelm in its sights again although this time the organization is comparing it with two other monoclonal antibodies that target the clumps of beta amyloid in the brain that many experts believe are the main cause of Alzheimer’s.

The two other monoclonal antibodies included in ICER’s review are Eli Lilly’s donanemab and Eisai's lecanemab. The companies submitted applications for FDA approval of both agents late last year, and the regulatory agency is scheduled to make a decision on whether to approve them this year.

 on its website, ICER is accepting public comments on its scoping document for the three-drug review through Jan. 19. A draft evidence report is scheduled to come out May 10 andon August 15.

ICER's analysis is slated to include two as-yet unapproved monoclonal antibody treatments, donanemab and lecanemab, as well as Aduhelm (aducanumab).

ICER To Assess Aduhelm, Other Monoclonal Antibody Treatments for Alzheimer's  in 2022

FDA Approves Generic of Chantix, Pfizer's Smoking Cessation Drug

This is the first approval of generic version of Chantix, and it comes just weeks after a recall of the brand-name drug.

Apotex to Import Generic of Chantix from Canada

This is being done in coordination with the FDA to address the shortage created by the recall of Chantix. 

Express Scripts Releases List of 2022 Formulary Exclusions

Four products on the preferred list this year will be excluded next year.

Nonopioid Pain Therapeutic Achieves More Than 100 Formulary Approvals

Anjeso, a COX-2 inhibito, is a faster-acting injectable formulation of meloxicam. As amnm alternative to opiods, it reduces opioid use after surgery.

Application was submitted for both the 81 and 325 mg doses of the liquid-filled capsule formulation of aspirin.

Apotex's importation of Chantix (varenicline) and Express Scripts' formulary exclusions were among the best read articles this year that didn't concern COVID-19.

Peter Wehrwein

Articles

Paxlovid Has Hospitalization, Mortality Benefits Among the Vaccinated

Trikafta Effective But Costly, Says Prime Therapeutics

Researchers: Ancillary Services Would Comprise 20% of Medicare Spending on Aduhelm

ICER To Assess Aduhelm, Other Monoclonal Antibody Treatments for Alzheimer's in 2022

Best Read Articles on News Not Related to COVID-19 in 2021