Due to the complexity and fragility of biological drug products, several challenges exist in their formulation development. Excipients are added to increase product stability, maintain tonicity, and facilitate drug delivery. The potential implications of these additive substances merit clinical consideration. We assessed the safety risk of excipients on the basis of their type and variability through an assessment framework, which quantifies excipient complexity in 230 biological formulations, and identifies excipient-related adverse events through published case reports. A biologic on average contained 4.45 excipients, half of that found in oral medications. The frequency distribution was heavily skewed towards the most commonly occurring excipients: water (40.4%), sodium chloride (38.3%), polysorbate 80 (28.7%), sucrose (24.4%), and mannitol (20.9%), with 44.4% of formulations not listing the concentration of the most commonly occurring inactive ingredients. A literature search revealed only 17 case reports of excipient-related adverse events, suggesting the need for more clarity for clinicians on the safety of chemical additives. These cases included injection site reactions, anaphylaxis, hyperglycemia, and acute renal failure. With the expansion of the biopharmaceutical market, it is important to consider the safety data of biologic excipients, so that therapy can be tailored appropriately for a specific patient.

Background and objectives

Durvalumab and atezolizumab are approved as first-line therapy in extensive-stage small-cell lung cancer. Although cost-effectiveness analyses compared these immunotherapy drugs with standard chemotherapy-alone regimens, no head-to-head cost-effectiveness comparisons for these treatments exist. The aim of the present analysis is to determine the cost-effectiveness of durvalumab and atezolizumab as first-line therapy for extensive-stage small-cell lung cancer from the US payers' perspective.

Methods

This study is based on two placebo-controlled, phase 3 clinical trials: CASPIAN and IMpower133. A Markov model was developed to simulate the three health states: progression-free survival, progressed disease, and death in patients with extensive-stage small-cell lung cancer. Transition probabilities were estimated from the clinical trial survival curves and extended with life-time modelling. Health utilities and direct costs of adverse event treatment were included. Main outcome was the incremental cost-effectiveness ratio (ICER) using quality-adjusted life-years saved (QALYS). Sensitivity analysis was performed to assess the impact of variables on the ICER.

Results

Durvalumab group has a cost of $187,503 with an effectiveness of 1.08 while atezolizumab has a cost of $160,219 and an effectiveness of 0.932. Durvalumab is not cost-effective compared to atezolizumab with an ICER of $165,182 QALYS, which is over the willingness-to-pay threshold of $150,000. The model was most sensitive to durvalumab cost and the cost of treating durvalumab adverse effects.

Conclusions

With the ICER of durvalumab treatment group being very close to $150,000, setting a higher willingness-to-pay threshold or decreasing the drug cost through contract pricing can increase the cost-effectiveness of durvalumab compared to atezolizumab.