Pfizer (Netherlands)

Background/Objectives: Infant pneumococcal conjugate vaccines (PCV) have significantly reduced pneumococcal morbidity and mortality. Newer vaccines, 15-valent (PCV15) and 20-valent (PCV20), offer broader serotype coverage, potentially preventing more disease. This study estimated the number needed to vaccinate (NNV) to prevent one disease outcome for infant PCV20 and PCV15 programs versus 13-valent PCV (PCV13). Countries from Europe, the Asia-Pacific, and the Americas were included. Methods: A multi-cohort, population-based model estimated the cumulative NNVs for infant programs with PCV20 and PCV15 relative to PCV13 in 21 countries. Outcomes included overall pneumococcal case, hospitalization, and death. The ratio of PCV15 NNVs to PCV20 NNVs was calculated. Probabilistic sensitivity analysis (PSA) and scenario assessments tested results' robustness. Results: Across 21 countries, the median of country-specific NNV estimates to prevent one pneumococcal case was 13 with PCV20 and 80 with PCV15. Median NNVs to prevent a hospitalization or death were 44 and 568 with PCV20 and 203 and 2203 with PCV15, respectively. PCV20 demonstrated lower NNVs than PCV15 across all countries and outcomes. Median NNV ratios for PCV15 versus PCV20 were 5.1 (case), 4.5 (hospitalization), and 4.2 (death). No clear geographic differences were observed. PSA and scenario analyses indicated stable results with minimal deviations. Conclusions: Infant immunization with PCV20 is associated with lower NNVs than PCV15. To achieve the same disease reduction as PCV20, over five times as many children would need to be vaccinated with PCV15. These findings suggest PCV20 may offer greater public health impact compared with PCV15 in infant immunization programs.

Abstract Background Healthcare claims databases are commonly employed to evaluate the epidemiology, outcomes, and costs of disease. However, validated case-ascertainment methods are largely unavailable, and thus outcome definitions often differ in terms of codes, algorithms, and/or data fields used to identify patients with a given disease; consequently, findings across studies often vary. In this study, we explored—as an exemplar—the impact of alternative case-ascertainment methods on variability in rates of adult invasive pneumococcal disease (IPD). Methods A retrospective cohort design and the Optum Clinformatics DataMart (CDM; 2016-2019) were employed; the Optum CDM includes healthcare claims from a large commercial health plan in the United States. From the study population comprising adults aged ≥ 18 years, patients with IPD requiring hospitalization or ambulatory care only were identified using several alternative methods, which varied based on the algorithms and data fields (Table 1). Rates were calculated within age-specific subgroups, on an overall basis and by care setting, and were expressed per 100,000 person years (PYs). Results for two of the algorithms are presented herein. Results With Method #1, which limited attention to diagnoses from hospital/facility claims during the admission, rates of IPD requiring hospitalization ranged from 1.5 to 28.1 per 100,000 PYs across age groups; with Method #2, which also included diagnoses from non-facility claims during the admission, hospitalized IPD rates were higher by 37-43% (Figure 1). For IPD requiring ambulatory care only, rates were higher by 67-174% when case-ascertainment was based on a single ambulatory claim with diagnostic evidence, versus ≥ 2 claims with diagnostic evidence and ≥ 1 claim for antibiotic therapy. Conclusion Using adult IPD as an exemplar, findings from this evaluation suggest that practical differences in case-ascertainment methods may lead to large variability in disease rates from analyses utilizing healthcare claims databases. Findings also reinforce the need for validation studies and use of standardized methods. Disclosures Ahuva Averin, MPP, Pfizer Inc: Grant/Research Support Mark Rozenbaum, PhD, M.B.A., Pfizer: Stocks/Bonds (Public Company) Stephen I. Pelton, MD, CSL Seqirus: Advisor/Consultant|GSK: Grant/Research Support|GSK: Honoraria|Merck Vaccines: Grant/Research Support|Merck Vaccines: Honoraria|Pfizer, Inc.: Grant/Research Support|Pfizer, Inc.: Honoraria|Sanofi: Honoraria|Sanofi: DSMB, Adjudicator for RSV vaccine trial Rotem Lapidot, MD, MSCI, Merck: Advisor/Consultant|Merck: Grant/Research Support|Merck: Honoraria|Pfizer: Advisor/Consultant|Pfizer: Grant/Research Support|Pfizer: Honoraria Amanda C. Miles, MPH, Pfizer: Employee of Pfizer Inc.|Pfizer: Stocks/Bonds (Public Company) Lindsay Grant, PhD, MPH, Pfizer: Employee|Pfizer: Stocks/Bonds (Private Company) Alexander Lonshteyn, PhD, Pfizer: Grant/Research Support Maria J. Tort, PhD, Pfizer, Inc: Stocks/Bonds (Public Company) Jeffrey T. Vietri, PhD, Pfizer Inc: Employment|Pfizer Inc: Stocks/Bonds (Public Company) Derek Weycker, Ph.D., Pfizer Inc.: Grant/Research Support

A 20-valent pneumococcal conjugate vaccine (PCV20) was recently recommended for use among US children. We evaluated the cost-effectiveness of PCV20 among children aged 6years with chronic medical conditions (CMC+) and children aged 6years with immunocompromising conditions (IC) versus one and two doses of 23-valent pneumococcal polysaccharide vaccine (PPSV23), respectively. A probabilistic model was employed to depict 10-year risk of clinical outcomes and economic costs of pneumococcal disease, reduction in life years from premature death, and expected impact of vaccination among one cohort of children with CMC+ and IC aged 6years. Vaccine uptake was assumed to be 20% for both PCV20 and PPSV23. Cost per quality-adjusted life year (QALY) gained was evaluated from the US societal and healthcare system perspectives; deterministic and probabilistic sensitivity analyses (DSA/PSA) were also conducted. Among the 226,817 children with CMC+ aged 6 years in the US, use of PCV20 (in lieu of PPSV23) was projected to reduce the number cases of pneumococcal disease by 5203 cases, medical costs by US$8.7 million, and nonmedical costs by US$6.2 million. PCV20 was the dominant strategy versus PPSV23 from both the healthcare and societal perspectives. In the PSA, 99.9% of the 1000 simulations yielded a finding of dominance for PCV20. Findings in analyses of children with IC aged 6years in the USA were comparable (i.e., PCV20 was the dominant vaccination strategy). Scenario analyses showed that increasing PCV20 uptake to 100% could potentially prevent > 22,000 additional cases of pneumococcal disease and further reduce medical and nonmedical costs by US$70.0 million among children with CMC+ and IC. Use of PCV20 among young children with CMC+ and IC in the USA would reduce the clinical burden of pneumococcal disease and yield overall cost savings from both the US healthcare system and societal perspectives. Higher PCV20 uptake could further reduce the number of pneumococcal disease cases in this population.

Introduction: In February 2020, tafamidis became the first drug approved to treat adults with transthyretin amyloid cardiomyopathy (ATTR-CM) in Europe. However, the real-world treatment patterns of tafamidis 61 mg in Germany, including adherence rates, are not well studied. Methods: A non-interventional, retrospective, observational cohort study of German IQVIA TM longitudinal prescription data. Patients were statutory insured and received ≥1 prescription of tafamidis 61 mg between March 01, 2020 and August 31, 2021. Baseline characteristics were assessed descriptively. Treatment adherence was analysed using the modified medical possession ratio (mMPR) and proportion of days covered (PDC). Results: 989 patients received ≥1 tafamidis prescription, with a mean age of 77.8 years, 81.1% were male, and 22.9% were treated by a cardiologist (Table 1). Overall, there were 7,753 prescriptions for tafamidis 61 mg. Mean supply and follow-up duration (first to last prescription) were 9.1 months and 7.8 months, respectively. The most frequent prior and concomitant medications were loop diuretics (73.7% and 69.7%), beta blockers (67.5% and 57.0%), direct factor Xa inhibitors (54.7% and 53.3%), and statins (55.0% and 47.4%). 879 patients received ≥2 prescriptions. Among these, mean mMPR was 1.03 (93.4% had an adherence rate ≥80%) and PDC was 0.90 (87.1% had adherence rate ≥80%; Figure 1). Conclusions: Patients prescribed tafamidis 61 mg in Germany display very high adherence. Based on professional society recommendations and using real world data, we found opportunities for concomitant medication optimization in patients with ATTR-CM and treated with tafamidis.

Conventional cost-effectiveness analysis—i.e., assessing pharmaceuticals through a cost per quality-adjusted life year (QALY) framework—originated from a societal commitment to maximize population health given limited resources. This "extra-welfarist" approach has produced pricing and reimbursement systems that are not well- aligned with the unique considerations of orphan drugs. This framework has been slow to evolve along with our increased understanding of the impact of rare diseases, which in turn has complicated the assessment of orphan drugs meant to treat rare diseases. Herein, we (i) discuss the limitations of conventional cost-effectiveness analysis as applied to assessing access to, as well as the pricing and reimbursement of, orphan drugs, (ii) critically appraise alternative and supplemental approaches, and (iii) offer insights on plausible steps forward.

BackgroundPatients with transthyretin amyloid cardiomyopathy (ATTR-CM) experience infiltrative cardiomyopathy and heart failure symptoms requiring costly hospitalizations. The Transthyretin Amyloidosis Cardiomyopathy Clinical Trial (ATTR-ACT) demonstrated the efficacy of tafamidis on the frequency of cardiovascular (CV)-related hospitalizations in patients with ATTR-CM.PurposeAs length of stay can affect the total hospitalization burden, our study aimed to better understand the impact of tafamidis on the number of CV-related hospital days avoided in the management of ATTR-CM patients.MethodsData from ATTR-ACT were used to calculate the total burden of CV-related hospitalization (days) by treatment arm in this post hoc analysis.ResultsIn the total trial population, patients receiving tafamidis had significantly fewer CV-related hospitalizations per year (relative risk reduction [RRR] 0.68; 0.4750 vs. 0.7025, p < 0.0001) and a shorter mean length of stay per CV-related hospitalization event (8.6250 vs. 9.5625 days) than patients receiving placebo. Taken together, tafamidis prevented 2.62 CV-related hospitalization days per patient per year. A subgroup analysis showed that with earlier treatment initiation of tafamidis, the annual number of CV-related hospitalizations was significantly lowered by 52% compared with placebo (RRR 0.48; 0.3378 vs. 0.7091, p < 0.0001). With 1.14 fewer days per hospitalization, tafamidis reduced the annual number of CV-related hospitalization days by 3.96 days per New York Heart Association class I/II patient.ConclusionsIn patients with ATTR-CM, tafamidis was associated with a lower rate of CV-related hospitalizations and shorter length of hospital stay. Timely diagnosis and treatment with tafamidis could further decrease the total number of CV-related hospitalization days per year.CLINICALTRIALS.gov IdentifierNCT01994889.

ABSTRACT Background: Currently literature on the impact of patent expiry on drug prices is lacking. Objective: To determine the impact of patent expiration and generic entry on drug prices in the Netherlands. Methods: Prescription and price data from 1999 up to and including December 2016 were collected from two national databases. The overall price ratio of drugs prices up to 48 months after patent expiration was compared to the price in the month before expiry. Sub-analyses were performed to provide insights in generic uptake, length of market exclusivity and price development for originators and generics separately. Results: In total 250 drugs faced patent expiration during the study period. Forty-eight months after patent expiration the median price ratio decreased to 0.59 (IQR = 0.23–0.86) compared to the month prior patent expiry. Major differences in price developments were observed depending on the level of revenue prior to patent expiration and the time of patent expiration with ratios ranging from 0.08 (IQR = 0.07–0.16) to 0.81 (IQR = 0.62–0.97). Prior to patent expiry, the price decreased by 2.3% annually while having market exclusivity for 11.3 years on average. Conclusion: This study showed that the median drug price after patent expiration decreased by 41% after 4 years. The results of this study can be used to provide more reliable estimates on drug prices over its lifecycle and can be implemented in economic evaluations to inform the cost-effectiveness and long-term budget impact of new drugs.

In a randomized trial (ie, Comparison of Low-Molecular-Weight Heparin versus Oral Anticoagulant Therapy for the Prevention of Recurrent Venous Thromboembolism in Patients with Cancer [CLOT]) that evaluated secondary prophylaxis of recurrent venous thromboembolism (VTE) in patients with cancer, dalteparin reduced the relative risk by 52% compared to oral vitamin K antagonists (VKAs; hazard ratio = 0.48, P = .002). A recent subgroup analysis in patients with moderate to severe renal impairment also revealed lower absolute VTE rates with dalteparin (3% vs 17%; P = .011). To measure the economic value of dalteparin in these populations, a pharmacoeconomic analysis was conducted from the Dutch health-care system perspective. Resource utilization data contained within the CLOT trial database were extracted and converted into direct cost estimates. Univariate analysis was then conducted to compare the total cost of therapy between patients randomized to dalteparin or VKA therapy. Health state utilities were then measured in 24 members of the general public using the time trade-off technique. When all of the cost components were combined for the entire population (n = 676), the dalteparin group had significantly higher overall costs than the VKA control group (dalteparin = €2375 vs VKA = €1724; P < .001). However, dalteparin was associated with a gain of 0.14 (95% confidence interval [CI]: 0.10-0.18) quality-adjusted life years (QALYs) over VKA. When the incremental cost was combined with the utility gain, dalteparin had a cost of €4,697 (95% CI: €3824-€4951) per QALY gained. Secondary prophylaxis with dalteparin is a cost-effective alternative to VKA for the prevention of recurrent VTE in patients with cancer.