PATIENT SAFETY and quality improvement in the US health care system have been the focus of national reports.^1,2 These reports have called for redesigning the health care system from the perspective of optimizing responsiveness to patients' needs. When the needs are related to the use of medications, patients benefit from collaborative efforts between physicians and pharmacists toward achieving intended goals of drug therapy while avoiding or minimizing adverse consequences. Several methods of effective collaboration in drug therapy management have been described.^3- 5

Background The past 10 years witnessed a significant increase in the approval of cellular and gene therapy products worldwide. The US Food and Drug Administration (FDA) approved 3 gene therapy products within the last 4 months of 2017. The objective of this study was to examine the approval characteristics, discontinuations and cost of all cellular and gene therapy products approved worldwide. Data and Methods We conducted an electronic search of approved cell and gene therapy products from the databases of the main drug regulatory agencies including the US Food and Drug Administration, the European Medicines Agency (EMA), the Korea Ministry of Food and Drug Safety (MFDS), and Japan’s Pharmaceuticals and Medical Devices Agency, China Food and Drug Administration, Ministry of Health and Social Development-Russia, Health Canada, and the Food and Drug Administration of the Philippines. We also searched the literature using MEDLINE/PubMed, Cochrane Library, Google Scholar and EMBASE databases. Cost information from the US was derived from the Reb Book (Truven Health Analytics). Costs from Europe were derived from Health Technology Assessments and from public sector, financial news and company’s web pages. Where available, we also obtained cost for products approved in other countries from public sector, financial news and company’s web pages. All cost data were converted to USD. Results There were 52 cell and gene therapy products marketed in the world as of September 2018. Of these, 39 (75.0%) were cell therapy medicinal products and 13 (25.0%) were gene therapy medicinal products. Of the approved products, 29 (74.3%) cell and 8 (61.5%) gene therapy products were first approved in the past 10 years (2008-present). Korea had the greatest number of approved cellular therapy-19 followed by US-12, Japan -4, Europe -3 and Canada -1. While Europe had the highest number of approved gene therapies - 5 followed by US - 3, China -2 and Korea, Russia and Philippines one each. Overall, 8 (66.7%) of the approved gene therapy products were granted orphan designation. Three products approved by the EMA were withdrawn or discontinued from the market. Of them, 2 remain currently marketed in the US. Cost of treatment from Gene therapy in US ranged from $447600 to $1,020,000 while in Europe the range was $370000 to $962890. Gene therapies outside US and Europe were relatively cheaper. Cell therapies in North America had a price range from $30,370-$200,000, European cell therapies ranged from $17,658-$105,000. Conclusion In the study period, more autologous cell therapy products were approved than allogenic agents. The cost of gene and cell therapy drugs is much higher in the EU and North America in comparison to Asia. Majority of the gene therapies received orphan designation by the regulatory authorities and had conditional approvals while less than a quarter of cellular therapies received the orphan designation. Most of the gene therapies are approved for rare diseases with smaller patient population, companies find it difficult to make profits which results in market withdrawal of the therapies.

The increasing number and high prices of orphan drugs have triggered concern among patients, payers, and policymakers about the affordability of new drugs approved using the incentives set by the Orphan Drug Act (ODA) of 1983. This study evaluated the factors associated to the differences in the treatment cost of new orphan and non-orphan drugs approved by the FDA from 2017 to 2021. A generalized linear model (GLM) with the Gamma log-link analysis was used to ascertain the association of drug characteristics with the treatment costs of orphan and non-orphan drugs. The results of the study showed that the median and interquartile range (IQR) drug cost was USD 218,872 (IQR = USD 23,105) for orphan drugs and USD 12,798 (IQR = USD 57,940) for non-orphan drugs (p < 0.001). Higher market entry prices were associated with biologics (108%; p < 0.001), orphan status (177%; p < 0.001), US sponsor companies (48%; p = 0.035), chronic use (1083%; p < 0.001), treatment intent (163%; p = 0.004), and indications for oncology (624%; p < 0.001) or genetic disorders (624%; p < 0.001). Higher market entry treatment cost for newly approved drugs were associated with biologics, orphan status, US sponsor companies, chronic use, therapeutic intent, and indications for oncology or genetic disorders.