Экономические последствия эгранатамаба для лечения пациентов с повторной или рефрактной миеломой.

Introduction

Multiple myeloma (MM) is an incurable disease, the second-most common hematologic malignancy, and the 14th most common cancer in the United States (US), 1 accounting for an estimated 35,730 new cancer cases and 12,590 cancer deaths in 2023. 2 The majority of people diagnosed with the disease are 65 years of age or older. 3 , 4

Although MM survival rates have improved with the introduction of targeted agents such as proteasome inhibitors (PI; bortezomib, carfilzomib, and ixazomib), immunomodulatory drugs (IMiD; lenalidomide and pomalidomide), and anti-CD38 monoclonal antibodies (mAb; daratumumab and isatuximab), as well as combination therapies, most patients eventually relapse and/or become refractory to the disease. 5 , 6 Survival rates for the relapsed or refractory MM (RRMM) population decrease with increasing lines of therapy (LOT), from a median survival of 9.2 months after three to four prior LOTs to 5.6 months after five or more prior LOTs. 7 In patients who have been exposed to, or have become refractory to, at least one PI, one IMiD, and one anti-CD38 mAb, defined as triple-class exposed (TCE) and triple-class refractory (TCR) MM, respectively, prognosis is even poorer due to the diminishing number of available treatment options. 8 , 9

In patients with TCE MM, chimeric antigen receptor T-cell (CAR T-cell) therapies (ciltacabtagene autoleucel [cilta-cel] and idecabtagene vicleucel [ide-cel], both approved by the US Food and Drug Administration [FDA]) 10 , 11 and bispecific antibodies (teclistamab, talquetamab, and elranatamab) 12–14 have shown high and durable responses, as well as prolonged progression-free survival (PFS) and overall survival (OS). 15 , 16 Both drug classes, as well as selinexor plus dexamethasone, are recommended in the National Comprehensive Cancer Network guidelines to treat TCE MM. 17 In clinical practice, however, many physicians continue to rely on regimens containing PIs, IMiDs, or mAbs. 8 , 15 , 18

The complex nature of treatment for RRMM has also led to a substantial and cumulative economic burden for payers and patients, particularly in a heavily treated population. 19 , 20 Although RRMM comprises a relatively small population, the per-patient, disease-related cost is high and increases with progression, 19 , 21 with a mean monthly cost reported to be over $31,800 for patients who initiate a fourth line of therapy. 19 Several studies have attributed the high costs to drug and administration costs 22–24 and the ability of novel agents to prolong PFS and OS. 25 , 26

Elranatamab, a novel, bispecific antibody that binds B-cell maturation antigen (BCMA) on myeloma cells and the CD3 receptor on the surface of T cells, received accelerated FDA approval in August 2023 to treat patients with TCE MM who have received at least four prior LOTs based on results from the MagnetisMM-3 trial ( NCT04649359 ). 14 MagnetisMM-3 is an ongoing, Phase 2, open-label, multicenter, non-randomized trial investigating the clinical efficacy of elranatamab for the treatment of TCR MM. 27 Results in patients with no prior BCMA-targeted treatment (Cohort A) showed an objective response rate of 61.0% 27 and a median PFS (mPFS) of 17.2 months. 28 At a follow-up of 34 months, median duration of response was not reached, and median OS (mOS) was 24.6 months. 29

The objective of this analysis was to estimate the budget impact in terms of total incremental cost, per member per month (PMPM) cost, and per patient per month (PPPM) cost of adding elranatamab for the treatment of adults with RRMM who have received at least four prior LOTs including a PI, an IMiD, and an anti-CD38 mAb from both the US commercial payer and Medicare perspectives. In addition, total cost of care and cost per months of PFS analyses of the available treatment alternatives were conducted to compare economic value. Both analyses are of key interest to US payers.

Methods

Model Structure

A budget impact model (BIM) was developed in Microsoft Excel to estimate the costs of introducing elranatamab as a treatment option for patients with TCE MM who have received at least four prior LOTs from both the US commercial payer and Medicare perspectives ( Figure 1 ). Population inputs were based on published epidemiology data and a large US real-world study. Patients in the model were allocated to different primary treatment groups based on the estimated market share data each year. The number of patients treated with each drug in the scenario without elranatamab (scenario 1) and with elranatamab (scenario 2) was calculated separately. The model considered direct costs including drug and administration for both primary and subsequent treatments, adverse event (AE) management, and disease management (monitoring tests, medical resource use [MRU], and end-of-life cost) based on clinical trial data, published literature, and government databases. The budget impact to the US payer was the difference in expected expenditures between the two scenarios. The model used a three-year time horizon with no discounting.

The BIM was developed in accordance with guidelines from The Professional Society for Health Economics and Outcomes Research Task Force Report for Budget Impact Analysis. 34 Data collection was conducted by January 16, 2024.

Model Inputs

Eligible Population

The BIM started with a hypothetical health plan population of one million members from both a US commercial and Medicare perspective. The model assumed the age distribution of the population based on US Census Bureau statistics where 12.65% (commercial) and 87.13% (Medicare) were older than 64 years. 30 The yearly number of MM patients was determined by multiplying the estimated population with the MM prevalence for each age group as sourced from the Surveillance, Epidemiology, and End Results Program database (≤64 years old: 0.02%, >64 years old: 0.20%) 2 and then multiplied by the share of patients with TCE MM who received at least four LOTs within the MM population (3.31%), sourced from a large US real-world study. 33 All patients were assumed to receive treatment. An annual population growth rate of 0.35% was assumed. 30

Treatment Parameters

Treatment Alternatives

The primary treatments considered in the model were elranatamab, talquetamab, teclistamab, selinexor plus dexamethasone, ide-cel, and cilta-cel. In addition, a physician’s choice of treatment (PCT) basket from MAMMOTH, a US real-world evidence study was added to reflect recent common treatment practice of relying on regimens containing PIs, IMiDs, or mABs. 18 , 35 The three most frequently used drug combinations in this basket consisted of bendamustine, prednisone, dexamethasone, cyclophosphamide, etoposide, and cisplatin (29.0%); carfilzomib, cyclophosphamide, and dexamethasone (22.0%); and ixazomib, pomalidomide, and dexamethasone (17.0%). 7 , 18

Estimated market shares for scenarios 1 and 2 were based on market research and clinician opinion ( Table 1 ). In year 1, 43.0% of patients were assumed to receive the PCT basket with a decrease over time in scenario 1 to reflect lower proven effectiveness compared with the bispecific treatments for which market shares were consequently assumed to increase over time. CAR T-cell therapies (ide-cel and cilta-cel) were assumed to have a stable market share at 5.0% each year, reflecting high costs and limited accessibility. 36

In scenario 2, the market share for elranatamab was assumed to gradually increase from 6.0% in year 1, to 12% and 18% in years 2 and 3, respectively. The market shares for the other treatments were assumed to be proportionally reduced from scenario 1.

Drug and Disease Management Costs

The model considered costs for drug acquisition (primary and subsequent), AE management, and disease management (monitoring tests, medical resource use [MRU], and end-of-life cost). The key inputs are summarized in Supplementary Table 1 . Mean treatment duration (TD), PFS, and OS were estimated to determine the durations of these costs.

The mean length of primary treatment was estimated based on the reported median TD (mTD) from the respective trials, assuming a standard exponential distribution. 37 The estimated mean TD were 8.01 months for elranatamab, 12.26 months for teclistamab, 10.68 months for talquetamab (assumed to be equal in the absence of separate data for once weekly [QW] and once every two weeks [Q2W] dosages), and 2.99 months for selinexor plus dexamethasone. Treatment until progression was assumed for the PCT basket (3.77 months) since no mTD was reported in MAMMOTH. 18 , 35 The total primary treatment cost was obtained by multiplying the treatment cost per week with the mean TD and relative dose intensity (RDI). Treatment costs for ide-cel and cilta-cel were treated as one-time costs occurring at treatment outset.

Costs related to primary treatment included those for drug acquisition, drug administration, premedication, and bridging therapies for ide-cel and cilta-cel between apheresis and infusion of the therapy. The percentages of patients receiving bridging therapies were 87.5% and 75.3% for ide-cel and cilta-cel, respectively, as reported in the KarMMa 38 and CARTITUDE-1 39 trials. The dosage of the bridging therapies generally aligned with the dosage in the PCT basket or current clinical practice. 38 , 39 All drug package costs were the Wholesale Acquisition Costs derived from RED BOOK © 2023. 40 Drug administration costs were obtained from the Physician Fee Schedule issued by Centers for Medicare & Medicaid Services. 41 The model assumed no vial sharing and therefore included wastage.

In the model, elranatamab was administered 76 mg QW as investigated in MagnetisMM-3 27 and according to the US FDA label. 14 Patients received two step-up priming doses of 12 mg on cycle 1 day 1, then 32 mg on cycle 1 day 4, followed by 76 mg QW starting on cycle 1 day 8 in 28-day cycles. After six cycles, patients were assumed to switch to Q2W dosing according to the trial protocol (ie, beginning from cycle 7 day 1).

The dosages for the comparators were sourced from their corresponding trial publications and US FDA labels. 10–13 , 35 , 42–47 For talquetamab, the model assumed that 30.0% of the patients received treatment QW, and 70.0% received treatment Q2W, based on clinical opinion. Although a Q2W dosing schedule is available for teclistamab, it was not included because the reported median time for switching occurred at approximately 12.7 months 48 after the estimated mean treatment duration of 12.21 months.

The distribution and duration of subsequent treatments were sourced from the MagnetisMM-3 trial and were applied similarly to all primary treatments ( Supplementary Tables 1 and 2 ). 27 , 49 At the median follow-up of 15.0 months, 63.9% of patients with progressive disease had received subsequent treatment (primarily different combinations of PIs, IMiDs, and anti-CD38 mAbs) with a median treatment duration of 8.0 months. 49 Subsequent treatment started after progression and was capped by the length of mean post-progression survival (PPS), defined as mean OS minus mean PFS. The mean PFS and OS rates for elranatamab and for each comparator were obtained from parametric extrapolation (using Weibull distribution) based on the Kaplan–Meier curves in the respective clinical trials. 28 , 35 , 42–46 , 48 , 50

Disease management costs in the model included those for MRU (hospitalization, inpatient and outpatient visits), monitoring with tests for complete blood count and biochemistry tests, and end-of-life costs. In the PFS state, patients were assumed to have monthly physician visits and complete blood count and biochemistry tests for all primary treatments except ide-cel and cilta-cel. Additional hospitalization days for initial step-up dosing were assumed for elranatamab (five days), teclistamab (nine days), and talquetamab (QW, nine days; Q2W, 12 days), according to US FDA labels. 12–14 Different sets of MRU and monitoring tests were applied for cilta-cel and ide-cel, based on their respective US FDA labels 10 , 11 and Jagannath et al, 2023. 51 In the PPS state, patients were assumed to have a once-monthly physician visit, complete blood count test, and biochemistry test for all treatments. 52 An end-of-life cost was applied as a one-time cost if death occurred during the three-year assessment period. All costs were inflated to 2023 values ( Supplementary Table 1 ). 53

AE Costs

For all primary treatments, grade 3 and 4 AEs that occurred in at least 5.0% of patients were included in the model. The AE rates were sourced from each comparator’s clinical trial, 27 , 35 , 42–47 , 49 and the unit costs for treating each type of AE were sourced from the Healthcare Cost and Utilization Project (2018) based on International Classification of Diseases 10 th Revision codes. 54 Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) were identified as AEs of special interest for all bispecific antibodies and CAR T-cell therapies, and all grades were included in the model since these could have a considerable impact on costs. 55–57 AE costs were modelled as a one-time cost ( Supplementary Table 3 ). No AE costs were added to subsequent treatment costs as a simplifying assumption.

Outcomes

The primary outcomes of the model were the cost difference between scenarios 1 and 2 over three years, measured as the overall budget impact, per member per month (PMPM), and per patient per month (PPPM).

A cost-of-care analysis using descriptive statistical analysis was conducted to compare the total cost of care, PPPM, and the cost per mPFS over one and three years for each drug, based on median estimates for TD, PFS, and OS ( Supplementary Table 1 ). Using medians rather than means facilitates comparison across studies, as shown in other budget impact studies in MM, 25 , 58 without susceptibility to uncertainty with Weibull extrapolation, but likely underestimates the mean costs for all treatments. The cost of care per month of PFS was obtained by dividing total cost by the mPFS of each primary treatment where data were available.

Sensitivity Analyses

One-way sensitivity analyses (OWSA) were conducted to assess uncertainty in model parameters and to identify the parameters with the biggest budgetary impact on the PMPM outcome. In each run of the OWSA, one parameter was varied from its base-case value to its lower (−20%) and upper bound (+20%) of the base-case value where applicable.

Results

Budget Impact

In the base-case analysis, the estimated eligible populations in a hypothetical plan of one million members were 14 (commercial) and 60 (Medicare) patients per year, respectively.

From the commercial payer perspective, the introduction of elranatamab to the market was projected to result in a total cost increase of $553,607 (total cost in scenario 1: $16,936,346; scenario 2: $17,489,953) over three years, with a total incremental PMPM cost of $0.05 and total incremental PPPM cost of $3259. The addition of elranatamab was associated with an increase of $934,044 for primary drug and administration costs, an increase of $131,722 in AE-related costs, and a decrease in total costs for subsequent treatment and administration by $510,288 ( Table 2 ).

From a Medicare perspective, the budget impact equaled $2,351,515 (PMPM $0.20 and PPPM $3259) with increased costs for primary drugs and administration ($3,967,477) and AE-related costs ($559,503) and reduced cost for subsequent treatment and administration ($2,167,510). In all scenarios and across payer perspective, primary drug and administration costs accounted for the largest share of total costs followed by subsequent treatment and administration costs and AE management costs ( Table 2 ).

Across both perspectives, OWSA indicated that the main budget impact was the drug cost per pack of elranatamab, the RDI of elranatamab, the market shares of PCT, and the mean treatment duration of elranatamab ( Figure 2 [commercial] and Supplementary Figure 1 [Medicare]). From a US commercial perspective, PMPM increased to $0.07 with a 20% increase in the drug cost per pack of elranatamab or an RDI of elranatamab equal to 100% (instead of 86%) and to $0.06 with longer treatment duration (9.61, instead of 8.01) with elranatamab.

Cost-of-Care Analysis

The respective primary drug and administration cost ($272,702) and total cost per patient ($337,838) were lower with elranatamab over a one-year period compared with teclistamab, talquetamab, cilta-cel, and ide-cel but higher compared with selinexor plus dexamethasone and PCT. Primary drug cost was the main cost contributor for most of the treatments except for selinexor plus dexamethasone and PCT where subsequent treatment cost was also high. Lower hospitalization cost due to step-up dosing or infusion were seen with elranatamab compared with the other bispecific treatments and CAR T-cell therapies ( Table 3 ). Of the evaluable treatments, elranatamab ($19,642) had a lower cost per mPFS than talquetamab, teclistamab, selinexor plus dexamethasone, PCT, and ide-cel, but it was slightly higher than cilta-cel ( Table 3 and Figure 3 ).

The 3-year time horizon analysis produced results that were consistent with the 1-year analysis, with a lower cost per month of mPFS with elranatamab than teclistamab, selinexor plus dexamethasone, PCT, and ide-cel ( Table 3 and Supplementary Figure 2 ). Total costs and cost per months of mPFS for talquetamab and cilta-cel could not be assessed since mOS was not reached.

Discussion

Understanding the economic impact of adding new therapies is important for health care decision makers. The objective of this study was to estimate the budget impact of introducing elranatamab as a treatment alternative for TCE MM patients who have received at least four prior LOTs including a PI, an IMiD, and an anti-CD38 mAb as well as a cost-of-care comparison of the primary treatments. Based on hypothetical one-million-members US commercial and Medicare health plans respectively, elranatamab was projected to result in a total budget impact of $553,607 (PMPM $0.05) and $2,351,515 (PMPM $0.20) over three years. Across both perspectives, the inclusion of elranatamab as a treatment option was estimated to have a small to limited impact on the overall budget of US payers, partly explained by the small eligible patient population per million members (commercial: N = 14; Medicare: N = 60).

To the best of our knowledge, no BIM analysis has been conducted on BCMA agents like elranatamab among patients with RRMM in the US, and no previous studies compared the total cost of care and the cost per month of PFS across treatment classes in RRMM. A few recently published studies evaluated the BIM of including selinexor, ide-cel, or cilta-cel. The budget impact of introducing selinexor for the treatment of penta-refractory RRMM in a commercial US payer healthcare perspective was estimated to be $302,571 (PMPM: $0.025) over 3 years, 59 which is lower than our estimate but mainly explained by lower drug cost and shorter PFS and treatment duration with selinexor. BIM analyses of CAR T-cell therapies from the US payer healthcare perspective predicted a significant total budget increase of $13.4 to $14 million (PMPM $1.11) per year with introducing ide-cel 60 and somewhat lower with introducing cilta-cel, 61 reflecting the high treatment costs of CAR T-cell therapies.

In RRMM, as in our study, primary drug and administration costs accounted for the largest share of the budget across payer perspectives. Adding elranatamab to the formulary increased the primary drug and administration costs by $934,044 (commercial) and $3,967,477 (Medicare). This increase was explained by elranatamab largely replacing lower cost drug combinations represented by the PCT basket, which accounted for the largest market share (between 30% and 40%). These findings aligned with the OWSA results, where inputs related to elranatamab drug cost (eg, cost per pack, RDI, and mean TD) were key budget impact drivers. An increase in AE costs was also seen (commercial [$131,722]; Medicare [$559,503]).

However, the addition of elranatamab indicated potential cost savings by $510,288 (commercial) and $2,167,510 (Medicare) due to lower subsequent treatment and administration costs. In the base case analysis, mean PFS was estimated to 37.5 months, and therefore, no subsequent treatment costs were added with elranatamab over the evaluated 3-year projections as opposed to treatments like PCT where PFS and OS were shorter than 3-years and therefore included such costs. For similar reasons, cost savings by $3664 (commercial) and $15,563 (Medicare) from reduced PPS MRU and monitoring costs were also observed. Finally, elranatamab was associated with cost savings by $70,883 (commercial) and $301,088 (Medicare) due to no end-of-life costs during the 3-year assessment period.

Across both US commercial and Medicare systems, OWSA indicated that the drug cost of elranatamab (eg, price per pack, RDI and treatment duration) was the most influential factor. For instance, a 20% increase in the drug cost per pack of elranatamab resulted in PMPM increase from $0.05 to $0.07 (US commercial) and from $0.19 to $0.31 (Medicare). In addition, the PCT market share in scenario 1 was also an important budget driver, reflecting increased drug costs of elranatamab when replacing drugs in the PCT basket with lower drug costs and shorter treatment duration.

In the cost-of-care analysis, our study indicated a better economic value with elranatamab compared with many other primary treatments for RRMM. Over one year, the total cost of care and cost per month of mPFS with elranatamab ($337,838 and $19,642) was lower than other bispecific treatments, including talquetamab ($407,039 and $33,391) and teclistamab ($427,039 and $37,791), as well as ide-cel ($673,903 and $78,361). These results were mostly attributed to lower total drug costs with elranatamab, explained in turn by shorter treatment duration and lower RDI. Patients treated with elranatamab also had fewer hospital days during step-up dosing or infusion versus the other bispecific and the CAR T-cell therapies. Elranatamab had a lower total cost of care than cilta-cel (ie, $337,838 vs $615,630), but a higher cost per month spent in PFS (ie, $19,642 vs $ 17,640) explained by the shorter mPFS with elranatamab than cilta-cel (ie, 17.2 vs 34.9 months). Although, selinexor plus dexamethasone ($180,499) and PCT ($184,480) had a lower total cost of care than elranatamab explained primarily by lower drug costs, these treatments suggested a lower economic value ($48,784 and $65,886, respectively) compared with elranatamab, given shorter mPFS.

Limitations

The current BIM was developed to sufficiently capture features of the disease of interest, with inputs collected from appropriate sources including clinical trials, government databases, and published literature. However, the results of this analysis should be considered in the context of the following limitations. The BIM was developed from a payer perspective and did not consider high indirect costs related to long periods of drug administration that have been reported in patients with RRMM. 62

Some data (references collected until January 16, 2024) used in the current analysis were immature, eg mOS for elrantanamab, 28 talquetamab, 44 cilta-cel 47 , 50 were not reached or included significant censoring. As the BIM analysis was based on estimates of mean PFS and OS from Kaplan–Meier curves in clinical trials, updated analysis using more mature data could impact the results.

In addition, market shares in a three-year horizon are difficult to predict given the rapidly evolving treatment landscape in RRMM with potential arrival of new treatments. 63 As indicated by the OWSA, a lower uptake of other bispecific treatments would increase the budget impact of elranatamab if replacing lower cost drugs in the PCT basket, whereas a higher uptake of other bispecific and CAR T-cell therapies would decrease the budget impact, given lower costs with elranatamab.

Apart from grade 1–2 CRS and ICANs, which were deemed AEs of special interest, only costs of grade 3/4 AEs were included. However, patients with triple-refractory MM are heavily pretreated and more susceptible to AEs, and there may be other lower grade AEs, like hypogammaglobulinemia, which incur additional costs. Unfortunately, data on the incidence of hypogammaglobulinemia were limited and could not be included in this model. Future research with more complete data could explore these potential costs further.

Finally, for the bispecific regimens, the current analyses used dosing frequencies sourced from the respective labels. In the literature, it has been shown that lowering the dosing frequency of these regimens might lead to improved long-term safety without compromising efficacy in patients with RRMM. 27 , 64 These findings warrant further exploration into how the addition of elranatamab with lower dosing frequency impacts the RRMM formulary budget.

The cost-of-care comparison, and particularly the cost per month of mPFS, should be treated with caution, as results were descriptive, not based on randomized controlled trials, and patient characteristics were heterogeneous across studies. For example, patients in MagnetisMM-3 were older, more likely to have extramedullary disease, and almost all were TCR compared with patients in MajesTEC-1. 27 , 43 Adjusting for baseline characteristics would likely result in longer PFS and OS for elranatamab versus teclistamab, as recently shown in a matching-adjusted indirect treatment comparison of elranatamab and teclistamab. 65 However, similar adjustments to TD (not reported) would increase drug costs with elranatamab, affecting the comparative economic values of the treatments. Given several treatment options and combinations for RRMM, it was not possible to provide comparable adjusted analyses for all treatment options. Finally, an updated analysis, based on more mature OS data for all primary treatments, including bispecific antibody and CAR T-cell therapies, is warranted.

Conclusion

Our study suggests that introducing elranatamab to the US market for the treatment of patients with TCE MM would result in a minimal to small budget impact over three years, partly explained by a small eligible patient population. Over one and three years, the respective total cost of care with elranatamab was lower than the other bispecific and CAR T-cell therapies. The cost per month of PFS with elranatamab was lower than other therapies except for cilta-cel. Elranatamab has demonstrated promising benefits in terms of OS and PFS, and may support good economic value, providing patients with a novel treatment option for TCE MM.

Acknowledgments

This study was funded by Pfizer. Editorial support was provided by Kerry Garza, PhD, of Nucleus Global and funded by Pfizer. An abstract on this content was presented at ISPOR 2024 as a poster presentation with interim findings. The abstract was published in ‘Poster Abstracts’ in ISPOR: https://www.ispor.org/conferences-education/conferences/past-conferences/ispor-2024/program/program/session/intl2024-3900/138907 .

Funding Statement

Funding for this study was provided by Pfizer Inc.

Data Sharing Statement

Upon request and subject to review, Pfizer will provide the data that support the findings of this study. Subject to certain criteria, conditions, and exceptions, Pfizer may also provide access to the related individual de-identified participant data. See https://www.pfizer.com/science/clinical-trials/trial-data-and-results for more information.

Ethics Statement

Ethical approval was not required for this updated analysis as per federal regulations 45 CFR 46.104(d), since it utilized data from published phase 2 trials. Please refer to the respective trial publication for the ethical standards followed for the MagnetisMM-3 trial. 27

Author Contributions

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Disclosure

BS: participated on an advisory board for Pfizer. YL, YH, and IM: employed by Cytel, which received funding from Pfizer in connection with the development of this manuscript. LB: participated on an advisory board for Pfizer. RS, DH, JH, and PH: employed by Pfizer and earn stock and/or stock options. AS: formerly employed by Pfizer and earns stock and/or stock options. The authors report no other conflicts of interest in this work.

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Associated Data

Data Availability Statement

Upon request and subject to review, Pfizer will provide the data that support the findings of this study. Subject to certain criteria, conditions, and exceptions, Pfizer may also provide access to the related individual de-identified participant data. See https://www.pfizer.com/science/clinical-trials/trial-data-and-results for more information.