MEDICAL POLICY – 5.01.536 Nulojix® (belatacept) for Adults Effective Date: Dec. 1, 2020 RELATED MEDICAL POLICIES: Last Revised: Nov. 3, 2020 11.01.523 Site of Service: Infusion Drugs and Biologic Agents Replaces: N/A Select a hyperlink below to be redirected to that section. POLICY CRITERIA | DOCUMENTATION REQUIREMENTS | CODING RELATED INFORMATION | EVIDENCE REVIEW | REFERENCES | HISTORY ∞ Clicking this icon returns you to the hyperlinks menu above. Introduction Nulojix® (belatacept) is a drug that suppresses the immune system to prevent the body from rejecting a transplanted kidney. It can be used for both right at the time of transplantation (induction) and long-term as a maintenance therapy. It was shown to be safe and effective in two large studies that compared it to other drugs used to prevent rejection after kidney transplant. In the study and based on the recommendation of the drug manufacturer, the drug needs to be given with other medications: all basiliximab, mycophenolate mofetil (MMF), and corticosteroids. Note: The Introduction section is for your general knowledge and is not to be construed as policy coverage criteria. The rest of the policy uses specific words and concepts familiar to medical professionals. It is intended for providers. A provider can be a person, such as a doctor, nurse, psychologist, or dentist. A provider also can be a place where medical care is given, like a hospital, clinic, or lab. This policy informs them about when a service may be covered. Policy Coverage Criteria This policy does not apply to members who are currently admitted to an acute hospital setting. We will review specific intravenous (IV) and injectable drugs for medical necessity for all ages. For those age 13 and older, we also will review the site of service for medical necessity. Site of service is defined as the location where the drug is administered, such as a hospital-based outpatient setting, an infusion center, a physician’s office, or at home. Drugs subject to site of service review addressed in this policy are: • Nulojix® (belatacept) Click on the links below to be directed to the related medical necessity criteria: Epstein-Barr Virus (EBV) seronegative or Prophylaxis of organ rejection, organs unknown serostatus other than kidney Prophylaxis of organ rejection, kidney Site of Service Site of Service Medical Necessity Administration Medically necessary sites IV infusion therapy of various medical or biologic agents will of service be covered in the most appropriate, safe and cost-effective • Physician’s office site: • Infusion center • These are the preferred medically necessary sites of service for • Home infusion specified drugs. Hospital-based outpatient IV infusion therapy of various medical or biologic agents will setting be covered in the most appropriate, safe and cost-effective • Outpatient hospital IV site. infusion department • Hospital-based outpatient This site is considered medically necessary for the first 90 days clinical level of care for the following: • The initial course of infusion of a pharmacologic or biologic agent OR Page | 2 of 14 ∞ Site of Service Medical Necessity Administration • Re-initiation of an agent after 6 months or longer following discontinuation of therapy* *Note: This does not include when standard dosing between infusions is 6 months or longer This site is considered medically necessary when there is no outpatient infusion center within 50 miles of the patient’s home and there is no contracted home infusion agency that will travel to their home, or a hospital is the only place that offers infusions of this drug. This site is considered medically necessary only when the patient has a clinical condition which puts him or her at increased risk of complications for infusions, including any ONE of the following: • Known cardiac condition (eg, symptomatic cardiac arrhythmia) or pulmonary condition (eg, significant respiratory disease, serious obstructive airway disease, %FVC ≤ 40%) that may increase the risk of an adverse reaction • Unstable renal function which decreases the ability to respond to fluids • Difficult or unstable vascular access • Acute mental status changes or cognitive conditions that impact the safety of infusion therapy • A known history of severe adverse drug reactions and/or anaphylaxis to prior treatment with a related or similar drug Hospital-based outpatient These sites are considered not medically necessary for infusion setting and injectable therapy services of various medical and biologic • Outpatient hospital IV agents when the site-of-service criteria in this policy are not infusion department met. • Hospital-based outpatient clinical level of care Page | 3 of 14 ∞ Condition Medical Necessity Prophylaxis of organ Nulojix® (belatacept) is subject to review for site of service rejection in adult patients administration. receiving a kidney transplant Nulojix® (belatacept) may be considered medically necessary for the induction therapy (ie, immunosuppression immediately post-transplant) when used in combination with: • Basiliximab induction • Mycophenolate Mofetil (MMF) • Corticosteroids Nulojix® (belatacept) may be considered medically necessary for maintenance therapy (ie, immunosuppression post- induction) when used in be combination with: • Mycophenolate Mofetil (MMF) • Corticosteroids Patient must have seropositive test result for Epstein-Barr Virus (EBV). Note: Patients should be monitored for new or worsening neurological, cognitive, or behavioral signs and symptoms. Prophylaxis of organ Nulojix® (belatacept) is subject to review for site of service rejection in transplanted administration. organs other than kidney The use of Nulojix® (belatacept) is considered investigational. Use in liver transplant patients is not recommended by the manufacturer due to increased risk of graft loss and death. EBV seronegative or Nulojix® (belatacept) is subject to review for site of service unknown serostatus administration. Nulojix® (belatacept) is contraindicated for use in patients who are EBV seronegative or with unknown serostatus because the risk of PTLD (post-transplant lymphoproliferative disorder) is particularly increased in patients who are EBV seronegative. Page | 4 of 14 ∞ Investigational The use of Nulojix® (belatacept) in patients under the age of 18 for any indication is considered investigational because there have been no studies to support use, safety, and efficacy in pediatric patients. Length of Approval Approval Criteria Initial authorization Nulojix® (belatacept) may be approved up to 6 months. Re-authorization criteria Future re-authorization of Nulojix® (belatacept) may be approved up to 12 months as long as the drug-specific coverage criteria are met and chart notes demonstrate that the patient continues to show a positive clinical response to therapy. Documentation Requirements The patient’s medical records submitted for review for all conditions should document that medical necessity criteria are met. The record should include the following: • Office visit notes that contain the type of transplant, EBV serostatus, concurrent medication use, relevant history and physical evaluation Coding Code Description HCPCS J0485 Injection, belatacept (Nulojix®), 1 mg Note: CPT codes, descriptions and materials are copyrighted by the American Medical Association (AMA). HCPCS codes, descriptions and materials are copyrighted by Centers for Medicare Services (CMS). Related Information Page | 5 of 14 ∞ Nulojix® (belatacept) inhibits T lymphocyte proliferation by binding to CD80 and CD86 on antigen-presenting cells, which blocks CD28 co-stimulation of the T cell. It also inhibits the production of interleukin-2&4, interferon-, and TNF-α. Immunologic rejections are mostly mediated by activated T lymphocytes. In primate models, graft survival was extended and anti- donor antibodies were diminished. Nulojix® (belatacept) has also been studied and is considered off-label in islet cell transplantation in type 1 diabetic patients and liver transplant patients; the latter is warned against in labeling. Nulojix® (belatacept) has the advantage of not requiring therapeutic drug monitoring, due to its predictable PK profile in trials among both healthy and kidney transplant patients. Bioavailability is 100%, the PK profile is linear and the exposure increased proportionately to doses of 1 go 20 mg/kg. In an extended phase 2 trial at 5 mg/kg, the measured Cmin was consistent from year 1 through 5 (Cmin range of 3.43-4.85 mcg/mL). A trend of higher clearance was found among patients with higher body weight. Subgroups determined to have no effect on clearance included age, gender, race, renal function, hepatic function, diabetes, and concomitant dialysis. Table 5 from the package insert (previous page) summarizes PK variability among healthy and post-transplant patients. The FDA approved dose is 10mg/kg on day 1, day 5, week 2, week 4, week 8, week 12, and 5 mg/kg every 4 weeks thereafter. Renal Transplantation Renal transplant is considered for most patients when the glomerular filtration rate (GFR) falls below 10 mL/min, while renal failure is considered permanent when the GFR reaches this level or a serum creatinine exceeds 8 mg/dL. After transplantation, the survival of the graft and patient continues to be a challenge, and many therapies are targeted to help prevent rejection of the graft by the host’s immune system. Both dialysis and renal replacement therapy are options once the patient reaches end stage renal disease (ESRD). ESRD is most frequently caused