Integrating Price Benchmarks and Comparative Clinical Effectiveness to Inform the Medicare Drug Price Negotiation Program.

OBJECTIVES: By September 2024, the Centers for Medicare and Medicaid Services (CMS) will publicly report the negotiated prices (Maximum Fair Prices) for the first 10 drugs selected for price negotiation. We estimate initial price offers based on net prices, statutorily defined ceilings, and comparative effectiveness data for the 10 drugs and their therapeutic alternatives. METHODS: We utilized net prices and other price benchmarks for the 10 drugs and their therapeutic alternatives. We searched for data on comparative clinical effectiveness for the primary indications. We outlined a range of plausible initial price offers based on CMS guidance and our interpretation of regulatory intent. RESULTS: For ibrutinib and ustekinumab, statutorily defined ceiling prices will likely determine the initial price offers. The integration of net pricing and clinical evidence from comparator branded products will inform the initial price offers for apixaban, empagliflozin, etanercept, and insulin aspart. Rivaroxaban and sacubitril/valsartan have therapeutic alternatives that are generics; therefore, CMS may apply a discount to current net prices. To achieve savings in the negotiation of dapagliflozin and sitagliptin, CMS will have to leverage additional negotiation factors because statutory defined ceilings and net prices of therapeutic alternatives are similar or higher. CONCLUSIONS: This analysis sheds light on important price benchmarks and clinical evidence factors for the determination of the initial price offers. Although we were not able to simulate the offer and counter-offer process, our findings provide a transparent and systematic way to produce initial offers that are consistent with CMS guidance.

Comparative Pharmacokinetics and Injection Site Histopathology in Nude Mice Treated with Long-acting Buprenorphine Formulations.

Two long-acting formulations of buprenorphine are commercially available as analgesics for rodents. However, these drugs have not yet been studied in nude mice. We sought to investigate whether the manufacturer-recommended or labeled mouse doses of either drug would provide and sustain the purported therapeutic plasma concentration of buprenorphine (1 ng/mL) over 72 h in nude mice and to characterize the injection site histopathology. NU/NU nude and NU/+ heterozygous mice were subcutaneously injected with extended-release buprenorphine polymeric formulation (ER; 1 mg/kg), extendedrelease buprenorphine suspension (XR; 3.25 mg/kg), or saline (2.5 mL/kg). Plasma concentrations of buprenorphine were measured 6, 24, 48, and 72 h after injection. The injection site was examined histologically at 96 h after administration. XR dosing yielded significantly higher plasma buprenorphine concentrations than did ER dosing at every time point in both nude and heterozygous mice. No significant difference in plasma buprenorphine concentrations were detected between nude and heterozygous mice. Both formulations yielded plasma levels of buprenorphine of over 1 ng/mL at 6 h; XR sustained buprenorphine plasma levels above 1 ng/mL for over 48 h, whereas ER sustained this level for over 6 h. Injections sites of both formulations were characterized by a cystic lesion with a fibrous/fibroblastic capsule. ER induced more inflammatory infiltrates than did XR. This study indicates that while both XR and ER are suitable for use in nude mice, XR has a longer duration of likely therapeutic plasma levels and induces less subcutaneous inflammation at the injection site.