1. Introduction

1.2. Importance of Medicare Coverage It is important to question and analyze the potential of Medicare coverage for new expensive medications like Lokelma because it assesses the potential to provide an improved form of treatment for elderly patients with hyperkalemia and questions the allocation of resources towards the management of this condition. With the average Medicare beneficiary having several chronic conditions and taking multiple medications, affordability becomes a significant issue. Access to Medicare Part D will provide an opportunity for patients to substantially lower the cost of treatment of hyperkalemia provided Lokelma is a preferred drug in a formulary due to it being newly developed, excessively costly, and potentially effective. Access to Medicare Part D will enable patients to try Lokelma by providing more affordable coverage options than Medicare Advantage or Medigap insurance. Additionally, it assesses the grander time horizon effect of taking a preventative measure to avoid complications of hyperkalemia like hospitalization where it is suggested that better management of hyperkalemia can reduce overall costs to the healthcare system. Overall, the coverage with Medicare and potential cost to patients are important topics to analyze regarding the potential of using Lokelma as the preferred medication to treat chronic hyperkalemia in elderly patients. (Pricing, 2020)

1.1. Overview of Lokelma Lokelma (sodium zirconium cyclosilicate) is used in adults with persistent hyperkalemia in the form of an oral suspension. Lokelma is an expensive medication that would be unaffordable for a majority of the patients it could potentially be useful for without insurance and especially Medicare coverage. The overall goal of this paper is to explore the effectiveness and potential of Medicare coverage for a relatively new and excessively expensive patient-directed therapy used to treat hyperkalemia known as Lokelma.

1.1. Overview of Lokelma

Lokelma, created by AstraZeneca, is a sodium zirconium cyclosilicate that is used for treating hyperkalemia. It works by repeatedly disturbing and discharging potassium from the blood into the gastrointestinal tract via ion exchange. Recently, AstraZeneca failed to attain a distinct Q-Code (J-Code) inside the hospital outpatient setting for Lokelma, which means Medicare patients receiving Lokelma will default their acquired DRG payment as a substitute of being able to ask for extra pass-thru payment with purchase out choice. J-Code and/or carve-out payment is important to hospitals, significantly for new medicine and the worth is crucial from a Medicare standpoint. As well as, frequent dialysis is a standard process for managing hyperkalemia patients, however AstraZeneca had a selected exclusion of dialysis patients from the ZS-9 ACLIVITY study to confirm Lokelma’s efficacy. AstraZeneca has since invested into a type of Lokelma known as a “mini-tablet” to increase treatment portability, notably for patients on-the-go and dialysis patients, which boasts the identical efficacy and safety of present formulations. AstraZeneca stated they may current additional data of this miniature formulation in future scientific congresses and will search discussion with regulatory authorities. It’s quickly unclear the trade effect and annual Medicare spending for Lokelma, however it might show a significant increase contemplating present limitations with ZS-9’s production, distribution, and price following launch. This is able to be due to excessive supply of Lokelma’s freely given sulfate and calcium polymers to Medicare ESRD patients and/or long term Lokelma use as opposed to Loop Diuretics to manage persistent volume overload in AVOID-HF. Particulars are subject to updates of new ZS-9 evidence, Q-Code acquisition, and additional congresses of the Lokelma mini-pill. Note that J-Code acquisition is also relevant to private payers, so proceed to track future Medicare Lokelma coverage for potential influence in managed care and industrial settings.

1.2. Importance of Medicare Coverage

Lokelma is an oral suspension being used to treat hyperkalemia. It works on the loop of Henle in the kidney to enhance the excretion of K+, blood levels can be seen to decrease as early as 1 hour, but effective treatment equally holds good with sustained results for both hyperkalemia and shifting back to normokalaemia. In the disease state, ECG changes and arrhythmias are real concerns with severe hyperkalemia. Access to affordable medications would be beneficial for patients, particularly in hyperkalemia as continued treatment may be required. 703 patients were studied over a 12-month period examining cardiovascular outcomes, there was no increase in risk of hospitalization due to heart failure or disease progression for those taking spironolactone and discontinuing from hyperkalemic events. Medicare insurance is available for those who meet the specific criteria for ESRD or those 65 years and older, it provides coverage for approximately 80% of healthcare costs. Due to the MVP program, a capitated payment system, there is fear that certain medications may become inaccessible. Medicare Humana is the provider for approximately 20% of patients involved in the EAGLE study, which they may have to leave if they are to partake in the study as it will no longer be supported. (Yeung et al.2021)

2. Medicare Coverage for Lokelma

Lokelma is now widely available and approved for sale in the United States as a treatment for hyperkalemia. However, the immense cost of Lokelma raises the question of whether or not it is covered by insurance and if so, how much of the cost is covered. For seniors who rely on Medicare, the concerns are the same: will Medicare cover Lokelma and how much will it cover? Currently, there are no clear-cut decisions as to whether or not Lokelma is covered by Medicare as it is a new drug introduced into the market. Typically, new drugs are quickly added to the market, and before long, Medicare provides coverage. This occurs via two methods: through Medicare Part B coverage and Medicare Part D coverage. Following a study of the evidence, if Lokelma were to become covered by Medicare, it would likely be through Part B coverage. This is expected as it is cheaper to the patient and the government in the long run through lessened hospitalization for high potassium levels – a service that Medicare Part B is geared to keeping costs down by covering. Part B coverage implies that the costs will be 80/20 split between the patient/government and will out a fixed reimbursement rate for physicians who administer Part B drugs. Coverage for an 80/20 payment split can also be found under a Medicare Advantage plan when Lokelma becomes coded as a Part B drug. Offers for manufacturer rebates to provide coverage for Lokelma under Part D Medicare drug coverage will also be considered.

2.1. Eligibility Criteria for Coverage

Hyperkalaemia can be caused by disease or medications. Chronic kidney disease is the most common cause of hyperkalaemia and patients with this condition are often taking multiple medications that can increase their risk of developing hyperkalaemia. Treating patients with higher comorbidity who are taking multiple therapies can be complex, and helping these patients improve quality of life via clinical management can be significant. Lokelma delivers robust potassium control, allows for RAASi treatment continuation and clinical trials have shown significant decrease in serum potassium levels compared to placebo, regardless of whether the patient was taking RAASi at baseline. A1703-5 and A1703-6 demonstrated that patients taking Lokelma are still able to initiate or continue use of RAASi, this is significant as withdrawal or inadequate dosing of RAASi contributes to a 58% risk of death post discontinuation in chronic kidney disease patients. Efficacy to this extent can improve patient prognosis and potentially minimize further potassium-related morbidity. This can lead to a reduction in unscheduled and emergency care service usage for hyperkalaemia related events. (Murphy et al., 2021)

2.2. Coverage Options for Lokelma

A discussion of the options for coverage of ZS-9 (Lokelma) revolves heavily around the site of care. For Medicare Part B, which only covers drugs under limited circumstances, and Medicare Part D, drugs are often administered in the hospital outpatient setting. Medicare Part B would cover Lokelma only if it were prescribed to patients with heart failure (resulting in pulmonary or peripheral edema) or patients with acute or chronic kidney disease. Though the payment amount for hospital outpatient care may initially appear significantly less than for physician’s office, recent legislation mandated reductions in Part B payment which would make Lokelma administration in an outpatient setting relatively more attractive. A 2008 ruling, often referred to as the “MMA transition,” created for a several year period a higher payment for drugs in the physician’s office or hospital outpatient setting than the payment for the same drug in the patient’s home. At this time, over 10% of patients receive dialysis for CKD in the patient’s home, and are Medicare Part D beneficiaries. The MMA transition may incentivize physicians to encourage certain patients who would normally take Lokelma as an outpatient administered drug to Medicare Part D beneficiaries who would take this drug at home (or to inpatient dialysis patients who would administer the drug in between treatments). This is because as of right now, ESRD patients are excluded from Medicare Part D coverage for ZS-9 (Lokelma specially approved for use in ESRD is addressed down the line). With the aforementioned MMA transition and the recently improved financial outlook for Medicare Part D plans that dispense low-cost drugs, ZS-9 manufacturers may consider devising insurance coordination strategies for ESRD patients to help them pay for drugs provided by Part D plans, and thus increase the ESRD patient market for Lokelma. This is considered under a section specific to ESRD patient coverage.

2.3. Limitations and Restrictions

Services provided by Medicare are subject to certain limitations and restrictions. The law imposes restrictions on the amounts that can be paid for covered services, and the amounts deemed “reasonable charges” are the limiting factors on payment. In cases where the fee schedule amounts are lower than the National Limit amounts, the limit on what the beneficiary can be charged is 115% of the fee schedule amount. This 115% limiting charge applies only to certain services. However, there is no balance billing allowed for services paid at the fee schedule rate. Fee schedule and National Limit amounts do not apply to services paid on a cost basis. Pricing is not applicable for drugs because they are paid on the basis of the average sales price. Finally, there are exceptions to these limitations and restrictions such as the Physician Services Increased Payment Act which allowed for increases in payment rates between 2000 and 2007. (Buchman et al.2020)

Despite the benefits offered by a Medicare-covered Part D drug, there are still restrictions in place. Patients can acquire coverage for Lokelma through a Medicare Advantage Plan (Part C) or a Medicare Prescription Drug Plan (Part D) if it’s on the plan’s formulary (list of covered drugs). Patients must be aware that receiving coverage for Lokelma through a Medicare Advantage Plan may have different restrictions and cost-sharing compared to a stand-alone Part D plan. Patients should communicate with their plan provider to find out more details on costs and coverage details.

3. Applying for Medicare Coverage

Applying for Medicare benefits can be a complex and sometimes frustrating process. Terms and conditions are subject to changes in legislation and interpretation, so the materials provided here should be used as a reference to the specific drug coverage policies. For a general overview of how to apply for Medicare benefits, visit [Link] Most Medicare drug plans have their own formulary, or list of covered medications. Each formulary must include a minimum of two drugs in the same category and class, but not all drugs are covered. If a patient is to receive coverage for a specific drug, the prescribing physician may need to provide a statement explaining that this particular medication is medically necessary. This can be the case for patients requiring a potassium binder, as many drugs in this category are alternatives to or generic formulations of the active drug, making them less likely to be covered. For specific information on the required documentation for a given medication, it is best to directly contact the patient’s Part D plan. The Medicare coverage process for specific medications can vary, but in many cases the prescriber will need to submit a written statement explaining the medical necessity of the drug, and a request for a formulary exception. This process can usually be completed by the physician or the patient’s Part D plan. If the statement and exception request are approved, the patient will likely be able to obtain the drug with partial or full coverage. For detailed information on how to request a formulary exception with a specific Part D plan, it is best to contact the plan directly.

3.1. Required Documentation

There are various forms of “required documentation” for an entity submitting a proposal that will determine whether Lokelma will be covered under Medicare. More specifically, CMS requires specific information to properly identify the product being reviewed (i.e., brand name, manufacturer, generic name, how it is packaged/available, etc.). This is crucial because Medicare coverage is specific to the product that is being reviewed. If there isn’t enough information to determine exactly what is being reviewed, this could lead to a determination for a different product than what was intended. CMS may also request a product label and or package insert. These are needed to further identify the product and how it is used. Having a package insert is crucial for a favorable coverage determination, as it provides information on the indicated population, how the product is administered, and suggested dosing. Finally, CMS may request clinical studies or published literature comparing the product in question to existing treatment options. This will help determine if the product is medically superior to existing options, as this will be a requirement for certain products to be eligible for coverage. Failure to submit any of these forms of documentation could result in an incomplete review, ultimately leading to a declination for Medicare coverage. If a “non oral” formulation of Lokelma were to become available, there could be an addition of further clinical documentation requirements. For example, if there is an IV formulation, but CMS determines that IV administration is not covered under Medicare, the product will not have an opportunity for a coverage determination. This happened with IV ferric gluconate (Ferrlecit®) in the past. From a physician in the Division of Nephrology at the University of Missouri and his colleagues were very disappointed after going through an extensive process applying for coverage, only to learn there was no window of opportunity to submit a proposal for a coverage determination. This was due to the fact that some years prior, CMS made a National Coverage Determination (NCD) that IV iron therapy was not reasonable and necessary in the treatment of ESRD. The decision to not allow a proposal was based off information from the NCD and no substantial documentation was requested. In this scenario, published literature comparing the IV iron therapy to the existing PPC oral iron therapy and its impact on patient outcomes would have been valuable, to see if IV iron was or was not in fact medically superior to the existing treatment options. This information would need to be presented in such a way that it could be used to request a reversal of the NCD, along with a request for reconsideration for the specific product. This could be a complex and extensive process, but if the option of a coverage determination is available, it would give the product a better opportunity to prove medical superiority and become covered under Medicare.

3.2. Application Process

There are two methods to gain approval of the Part D plan sponsor or Medicare Advantage (MA) organization. First, the Part D plan sponsor or MA organization and the manufacturer may request issuance of a National Coverage Determination (NCD) or a Local Coverage Determination (LCD) by submitting a formal written request to CMS. Second, if there is no NCD or LCD, the Part D plan sponsor or MA organization may submit an exception request involving a particular enrollee. An exception request is an extension of coverage that allows a Part D plan sponsor or MA organization to request additional time to make a formulary or utilization management exception, or to request an extension of an automatic exception period. An exception request is submitted through the Medicare Prescription Drug Redetermination Request Form or through the Health Insurance Benefits Agreement and Referral Form for MA organization enrollees. (Dusetzina et al.2022)

3.3. Timelines and Approval

The entire Medicare coverage determination process should be done in 180 days. Within 90 days of the request, CMS makes a decision regarding the sufficiency of the evidence for a Local Coverage Determination (LCD) by the Medicare contractor. If a decision favorable to the applicant’s point of view is not rendered by the contractor, the next level of appeal is triggered by filing a request for redetermination with the contractor, which must be done within 60 days of the LCD denial. The redetermination is then reviewed by the contractor who has 60 days to make a decision. If the redetermination is not in the applicant’s favor, the case is automatically forwarded to a Qualified Independent Contractor (QIC) and the amount in controversy amount is met for QIC review is now $160. Timeframes for a decision at the QIC level are within 90 days, however, they can be extended 14 days. If the QIC unfavorable, this amount in controversy requirement now triggers an Administrative Law Judge hearing and the case is placed on the docket. ALJ decisions must be made within 90 days of the request with the ability to be extended by 14 days. (Jin et al., 2022)The appeals process within the judicial system has varying time requirements, but in depth discussion of each level is beyond the scope of this article. Overall, if a decision is not made by a certain entity within the specified time, the applicant has the option to move to the next level of appeal. Thus, procedural fairness is maintained by time standards at each level of the appeals process. This is extremely beneficial to Medicare beneficiaries who are seeking a change in Medicare coverage policy and gives them closure on their issue within a reasonable amount of time.

4. Conclusion

There is recognition of the clinical and economic benefits to patients and the Medicare program by covering Lokelma. Lokelma offers a treatment option at various stages of CKD that can help avoid hospital admissions for SBC events. The Medicare ESRD and CKD population is especially susceptible to SBC events especially in the summertime. Covering Lokelma for this population can help avoid high cost medical events at a much lower overall cost to the program. Providing access to Lokelma for Medicare patients with ESRD and CKD can help avoid disruptions in their treatment regimens and progress to using alternative SBC event treatments that have higher safety risks and a higher overall cost. Under SS&C rules, payment under Part D for ESRD is required. AMCP will continue to follow this issue and work with industry stakeholders and Medicare officials to facilitate access to Lokelma for Medicare patients.

4.1. Benefits of Medicare Coverage for Lokelma

The Part D benefit provided under Medicare for Lokelma would enable renal patients who have hyperkalemia to receive an important advance in treatment access. Renal insufficiency is often a consequence of diabetes or cardiovascular disease, and up to half of patients with kidney failure develop hyperkalemia, which is a potentially life-threatening condition caused by increased potassium levels. The presence of hyperkalemia may exacerbate the progression of chronic kidney disease (CKD) and may be exacerbated by the use of medicines which are often necessary for the management of CKD and diabetes, including medicines that inhibit the renin-angiotensin-aldosterone system (RAAS), and/or potassium supplements. Since cardiac patients with hyperkalemia have to stop RAAS inhibitors and β-blockers which prevent heart failure and chronic kidney disease progression, the condition can result in increased morbidity, mortality and utilization of healthcare resources. Despite the harmful effects of hyperkalemia in renal and cardiac patients, the condition has often been under-treated because primary care physicians and specialists had few treatment options available and were reluctant to add another medicine or raise the dose of an existing medicine for fear of causing further potassium increases.

4.2. Ensuring Access to Lokelma through Medicare

Patients with hyperkalaemia who are Medicare eligible and Part D enrolled will have access to Lokelma to help manage their condition. Like with Lokelma, Veltassa and Patiromer will undergo a similar process to secure a HCPCS code but this will not occur before 2020. This essentially signifies that for the next four years, the introduction of Lokelma will have an extended period of market exclusivity to Veltassa and Patiromer provided they also have a HCPCS code to enable Part D coverage. What is crucial for Pharmas is that patients are able to access their drugs in a timely manner and market access is pivotal in achieving this. A HCPCS code enables patients to access Lokelma under an affordable copay through Part D plans in the Medicare space compared to trying to seek access under a medical benefit where patients may be subject to a higher coinsurance and Pharmas may need to provide free product via cost assistance programs. High coinsurance levels can also be a significant obstacle for patients trying to remain compliant on their drugs. In the Medicare space, a 30% or greater spread between the cost of a drug and a lower cost therapeutic alternative within the same class will trigger the need for automatic substitution under a Part D plan or the drug will risk losing access to patients. This essentially results in the higher priced drug becoming a non-preferred option with a large disincentive for prescribers and patients to continue utilizing this product. A HCPCS code and competitive pricing will also provide Lokelma with access to Medicare coverage gap discounts which is of benefit to patients.

References:

Pricing, P. D., 2020. REPORT TO CONGRESS. hhs.gov

Yeung, K., Dorsey, C.N. and Mettert, K., 2021. Effect of new Medicare enrollment on health, healthcare utilization, and cost: a scoping review. Journal of the American Geriatrics Society, 69(8), pp.2335-2343. [HTML]

Murphy, D., Ster, I. C., Kaski, J. C., Anderson, L., & Banerjee, D., 2021. The LIFT trial: study protocol for a double-blind, randomised, placebo-controlled trial of K+-binder Lokelma for maximisation of RAAS inhibition in CKD …. BMC nephrology. springer.com

Buchman, T.G., Simpson, S.Q., Sciarretta, K.L., Finne, K.P., Sowers, N., Collier, M., Chavan, S., Oke, I., Pennini, M.E., Santhosh, A. and Wax, M., 2020. Sepsis among medicare beneficiaries: 1. The burdens of sepsis, 2012–2018. Critical care medicine, 48(3), pp.276-288. lww.com

Dusetzina, S.B., Huskamp, H.A., Rothman, R.L., Pinheiro, L.C., Roberts, A.W., Shah, N.D., Walunas, T.L., Wood, W.A., Zuckerman, A.D., Zullig, L.L. and Keating, N.L., 2022. Many Medicare beneficiaries do not fill high-price specialty drug prescriptions. Health Affairs, 41(4), pp.487-496. [HTML]

Jin, G. Z., Lee, A., & Lu, S. F., 2022. Patient routing to skilled nursing facilities: The consequences of the medicare reimbursement rule. Management Science. [HTML]