Non-orphan Drugs Research Articles

Valuation of Medical Innovation Handling with Uncertainty and Risk.

Background: The purpose of this paper is to address how to handle uncertainty when performing an economic valuation of a medical innovation R&D project in orphan diseases from the perspective of the investor. Methods: We describe the specific uncertainty related to cash flows and the cost of capital for innovation in orphan diseases. The uncertainty in cash flows relates to sales, manufacturing and R&D costs, and probabilities of failure for each phase in the clinical trial program. We consider different net present values (NPVs) and higher standard deviations for orphan drugs compared to non-orphan drugs. Results: Numerical case base examples showed the differences in trade-off by an investor for R&D projects with differences in NPV and level of uncertainty. The investor will transfer the additional uncertainty in cash flows in a higher cost of capital. An alternative approach is the application of an "acceptability curve" based on a probabilistic sensitivity analysis, which displays the cumulative probabilities at a range of different values for the NPV. Finally, we consider uncertainty in the cost of capital itself by applying the Capital Asset Pricing Model (CAPM). Conclusions: In this paper, we described various types of uncertainty and explored various approaches to how to handle uncertainty in the economic valuation of medical innovation in orphan diseases. The bridging of health economics with economic valuation theory in the healthcare market is to our knowledge a novel approach for the valuation of medical innovation by investors.

The Health Benefits, Costs, and Cost-Effectiveness of Ultraorphan Drugs

ObjectivesTo examine ultraorphan drugs in terms of incremental health, costs, and cost-effectiveness compared with more prevalent disease drugs. MethodsWe identified Food and Drug Administration drug approvals from 1999 to 2019. For drugs approved for multiple indications, we considered each drug-indication pair separately. Utilizing Food and Drug Administration’s orphan drug designation and US disease prevalence, we categorized drug-indication pairs as: ultraorphan (<10 000 patients), “other” orphan (≥10 000 and <200 000), and nonorphan (≥200 000). We searched the PubMed database for cost-effectiveness analyses and comparative effectiveness studies. We excluded manufacturer-funded studies. We extracted estimates of incremental health gains in terms of quality-adjusted life-years (QALYs) and incremental costs associated with drug-indication pairs compared with the standard of care at the time of their approval. We compared QALY gains, added costs, and incremental cost-effectiveness ratios (ICERs) using the Kruskal-Wallis, Mann-Whitney U (MWU), and Kolmogorov-Smirnov (KS) tests. ResultsMedian incremental QALYs, costs, and ICERs differed across nonorphan, “other” orphan, and ultraorphan categories (Kruskal-Wallis P < .01). Compared with nonorphan drugs, ultraorphan drugs had larger QALY gains (0.700 vs 0.050, MWU P < .01, KS P < .01), larger costs ($172 231 vs $3360, MWU P < .01, KS P < .01), and larger ICERs ($1 216 184/QALY vs $114 061/QALY, MWU P < .01, KS P <.01). Compared with “other” orphan drugs, ultraorphan drugs had larger QALY gains (0.700 vs 0.310, MWU P =.65, KS P =.32), larger costs ($172 231 vs $69 308, MWU P = .03, KS P = .03), and larger ICERs ($1 216 184/QALY vs $223 472/QALY, MWU P <.01, KS P <.01). ConclusionsNovel ultraorphan drugs typically offer larger incremental health gains than drugs for more prevalent diseases, but because of their substantial added costs, are typically less cost-effective.

Societal preferences for granting orphan drugs special status in reimbursement decisions

BackgroundOrphan drugs, for patients with a rare disease, are increasingly available but often do not meet standard cost-effectiveness criteria for reimbursement. Consequently, policymakers regularly face the dilemma whether to relax these criteria for reimbursing orphan drugs. We examined whether—and why—there would be societal support for such differential treatment of orphan drugs. MethodsWe conducted a labelled discrete choice experiment in a sample of the adult population (n = 1,172) in the Netherlands. Respondents were presented with ten choices on whether to reimburse an orphan drug given that a non-orphan drug with similar characteristics would not be reimbursed, because it was not cost-effective, and asked to explain their choices. We used random-intercept logit regression models and inductive coding for analysing the quantitative and qualitative data. ResultsOf the respondents, 36.4% consistently chose for reimbursing the orphan drug, mostly because “everyone is entitled to live a healthy life and good quality healthcare”, and 17.3% consistently for not reimbursing the orphan drug, mostly because “[this] is unfair to patients with a common disease”. The remaining 46.3% made alternating choices and were more likely to choose for reimbursing orphan drugs when patients were aged between 1 and 70 years, had moderate disease severity, and considerable health gain from treatment. ConclusionsThis study finds considerable support but also strong preference heterogeneity amongst members of the public in the Netherlands for differential treatment of orphan drugs in reimbursement decisions, when these drugs do not meet common cost-effectiveness criteria. However, a substantial minority opposes differential treatment, mostly on moral grounds.

Partial Orphan Cancer Drugs: US Food and Drug Administration Approval, Clinical Benefit, Trials, Epidemiology, Price, Beneficiaries, and Spending

ObjectivesThe Orphan Drug Act (ODA) incentivizes drug development for rare diseases with limited sales potential. Partial orphans—drugs used to treat rare and common diseases—frequently turn into multi-billion dollar blockbusters. This study analyzes partial orphan cancer drugs’ development, approval, and economics. Methods170 drugs with US Food and Drug Administration approval for 455 cancer indications were identified (2000-2021). 110 full, 22 partial, and 38 non-orphan drugs were compared regarding their approval, benefits, trials, epidemiology, price, beneficiaries, and spending with data from regulatory documents, Global Burden of Disease study, and Medicare and Medicaid. ResultsFull orphans, relative to partial and non-orphans, were more frequently monotherapies for hematologic cancers supported by smaller single-arm trials treating diseases with a lower incidence and higher severity. The time from first to second indication approval was 1 year shorter for partial than full orphans. Full orphans offered a greater overall survival (median: 4.0 vs 2.8 vs 2.8 months, P < .001) and progression-free survival benefit (median: 5.1 vs 2.5 vs 3.6 months, P < .001). Monthly prices were higher for full and partial than non-orphan drugs (median: $17 177 vs $13 284 vs $12 457, P < .001). Beneficiaries (8790 vs 4390 vs 1730) and spending ($570 vs $305 vs $156 million) per drug were greater for partial than non-and full orphans. ConclusionsAlthough partial orphans’ benefits, trials, and economics are more similar to non-than full orphans, they receive all of the ODA’s benefits and are swiftly extended to new indications; resulting in greater spending. A maximum ODA revenue/patient threshold could limit expenditure on partial orphans.

Uptake of orphan drugs in the WHO essential medicines lists.

We evaluated the uptake of medicines licensed as orphan drugs by the United States Food and Drug Administration (FDA) or European Medicines Agency (EMA) into the WHO Model list of essential medicines and the WHO Model list of essential medicines for children from 1977 to 2021. We collated and analysed data on drug characteristics, reasons for adding or rejecting medicines, and time between regulatory approval and inclusion in the lists. We compared trends in listing orphan drugs before and after revisions to the inclusion criteria of the essential medicines lists in 2001, as well as differences in trends for listing orphan and non-orphan drugs, respectively. The proportion of orphan drugs in the essential medicines lists increased from 1.9% (4/208) in 1977 to 14.6% (70/478) in 2021. While orphan drugs for communicable diseases have remained stable over time, we observed a considerable shift towards more orphan drugs for noncommunicable diseases, particularly for cancer. The median period for inclusion in the essential medicines lists after either FDA or EMA first approval was 13.5years (range: 1-28 years). Limited clinical evidence base and uncertainty about the magnitude of net benefit were the most frequent reasons to reject proposals to add new orphan drugs to the essential medicines lists. Despite lack of a global definition of rare diseases, the essential medicines lists have broadened their scope to include medicines for rare conditions. However, the high costs of many listed orphan drugs pose accessibility and reimbursement challenges in resource-constrained settings.

The Orphan Drug Act at 40: Legislative Triumph and the Challenges of Success.

Policy Points The Orphan Drug Act (ODA) was the result of patient advocacy and by many measures has been strikingly successful. However, approximately 95% of the more than 7,000 known rare diseases still have no US Food and Drug Administration-approved treatment. The ODA's success led to sustained criticism of high drug prices, often for products that have orphan drug indications. Critics misconstrue the ODA's intent and propose reducing its incentives instead of pursuing policies focused on addressing broader prescription drug price challenges that exist in both the orphan and nonorphan drug market. Patients and their families will continue to defend the purpose and integrity of the ODA and to drive investments into rare disease research and clinical development.

HTA134 The Impact of Non-Comparative Data for Non-Orphan Drugs on HTA and Pricing Outcomes in Germany: Can an Added Benefit Ever be Proven?

HTA134 The Impact of Non-Comparative Data for Non-Orphan Drugs on HTA and Pricing Outcomes in Germany: Can an Added Benefit Ever be Proven?

Quality and quantity of data used by Health Canada in approving new drugs

BackgroundThis study examined multiple aspects about the approval of new drugs: the characteristics of the drugs, the quality and quantity of information that Health Canada discloses about the demographics of patients enrolled in clinical trials, the characteristics of the trial, and the type of review that it uses. It examines whether there have been changes in these measures between 1 September 2012 and 31 March 2022.MethodsA list of all new drugs approved, type of review used, and drug characteristics was generated from Health Canada annual reports. Therapeutic categories were identified from the World Health Organization Collaborating Center for Drugs Statistics Methodology. The Summary Basis of Decision documents of Health Canada were used to identify patient demographics in clinical trials and clinical trial characteristics.ResultsHealth Canada approved 326 new drugs for 407 indications. The percent of orphan drugs approved increased from 35.6 to 51.3%. The number of indications per drug decreased (p = 0.0817) as did the number of pivotal trials per drug (p = 0.0091). The percent of Phase 3 trials dropped from 76.3% in 2012–2015 to 64.8% in 2019–2022 (p = 0.005). There was also a statistically significant decrease in the percent of trials that were randomized, controlled, and blinded. The clinical trial characteristics of orphan drugs and the type of review used were both significantly different compared with non-orphan drugs. The percent of trials which had information about the number of patients enrolled, the percent of trials that provided the age of the patients, and the sex breakdown all significantly increased.ConclusionThe results show that there has been a change in regulatory standards that may be due to them becoming less rigorous, because of an adaptation to the number of orphan drugs being submitted or a combination of both reasons. At the same time, there has been some improvement in the transparency of data. Health Canada has recently embarked on a series of reforms in drug regulation and clinical trial management. These changes need to be closely evaluated to be sure that they enhance the efficacy and safety of new drugs.

Launch and Post-Launch Prices of Injectable Cancer Drugs in the US: Clinical Benefit, Innovation, Epidemiology, and Competition.

Rising cancer drug prices adversely affect patients' adherence and survival. We aimed to identify and quantify factors associated with launch prices and post-launch price changes of injectable cancer drugs in the US from 2005 to 2023. All anticancer drugs with US FDA approval between 2000 and 2022 were identified in the Drugs@FDA database. The sample was then restricted to cancer drugs covered under Medicare Part B (injectable drugs). Data characterizing each drug's clinical benefits, disease epidemiology, approved indications, competition, and price were obtained from FDA labels, the Global Burden of Disease study, and the Centers for Medicare and Medicaid Services. The association between launch/post-launch prices and collected variables was assessed in random-effects regressions. Of 170 cancer drugs with FDA approval between 2000 and 2022, we identified 66 (39%) injectable cancer drugs with quarterly price data from 2005 to 2023. In 2023, mean prices amounted to $27,688 per month, with an average price increase of 94% from 2005 to 2023. Launch and post-launch price changes were significantly associated with the treated disease epidemiology. A 1% decline in disease incidence was associated with a 0.2511% (p=0.008) increase in launch prices and a 0.0086% (p=0.032) annual increase in post-launch prices. Accordingly, launch prices were 120% (p=0.051) higher for orphan than non-orphan drugs, with 3% (p=0.008) greater annual post-launch price increases. Post-launch prices declined by up to -2% annually as new supplemental indications were approved for the same drug. We found no consistent association between launch/post-launch prices and the drugs' clinical benefit in terms of overall survival, progression-free survival, and tumor response. The market entry of new competitors was not associated with price reductions. 28 of 33 drug pairs within the same class had positive correlation coefficients. Pearson correlation coefficients were high (>0.80) for PD-1/PD-L1 inhibitors, CD38 antibodies, CD20 antibodies, HER2 antibodies, and mTOR inhibitors. Cancer drug prices regularly increase faster than inflation; however, there is no evidence that launch prices and post-launch price changes are aligned with the clinical benefit a drug offers to patients. In particular, patients with rare diseases experience greater price increases for their orphan drugs. There is no evidence that brand-brand competition results in drug price reductions.

HTA92 A Review and Evaluation of Successfully Reimbursed Orphan and Non-Orphan Drugs in Ireland

To analyse the number of drugs successfully achieiving National Centre of Phamacoeconomics (NCPE) reimbursement in 2022 with non-orphan drug status compared to orphan drug status, and to identify any impacts achieving orphan drug status might have on reimbursement success.

Orphan Drug Development Policies in India and the United States: A Comparison

Abstract: Background: A pharmacological agent known as an orphan drug was created to address rare or orphan diseases. The Food and Drug Administration (FDA) claims that the Orphan Drug Act has certainly encouraged the development of treatments for rare diseases. The Orphan Drug Act was passed in the United States in 1983 to encourage pharmaceutical companies to develop treatments for rare diseases. Global sales of orphan drugs are anticipated to increase at a Compound Annual Growth Rate (CAGR) of 12.3% from 2019 to 2024, which is roughly double the rate anticipated for the non-orphan drug industry. India has between 72 and 96 million people who are affected by rare diseases. There are no specific orphan drug laws in India. The Ministry of Health and Family Welfare of India established a National Policy for the Treatment of Rare Diseases in July 2017 (NPTRD). However, there were challenges to the execution of the policy. The Orphan Drug Act, which was passed on January 4, 1983, gave orphan medications legal status in the United States. The lack of orphan drug regulation hurts the Indian pharmaceutical businesses' ability to thrive economically. Contrarily, the US's orphan drug regulations have been effective in bringing therapies to people with rare disorders. The assessment of the scope and impact of orphan diseases, as well as a widespread awareness campaign about orphan diseases, are urgently needed in the current situation. Orphan drug development requires strong policies and initiatives from both public and private institutions. Materials and Methods: This review article is based on the information collected from various sources from FDA and NPTRD and the articles mentioned. Results: The different guidelines and regulations for the development and manufacture of orphan pharmaceuticals should be put into place to ensure that orphan diseases get the necessary treatment and care. Conclusion: The FDA regularly updates and the Orphan Drug Act provides direction for the overall rules and regulations in the United States. In India, being a semi-regulated market, there are no such specific rules and regulations regarding development. The National Policy for Rare Disease in India 2021 helps as a guidance document regarding the policies related to orphan drugs in India. Keywords: Orphan Drugs, Orphan diseases, Rare diseases, Initiative, Treatment.

Disentangling the Cost of Orphan Drugs Marketed in the United States

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.

Orphan drugs' clinical uncertainty and prices: Addressing allocative and technical inefficiencies in orphan drug reimbursement.

Legislations incentivising orphan drug development and scientific advances have made orphan drugs pharma's high-end favourite for the past two decades. Currently, around 50% of new marketing authorizations are for orphan drugs. For third-party healthcare payers ("payers") the rise of orphan drugs presents new challenges, including a high degree of uncertainty around clinical benefits and harms, a moderate effect size (for many orphan drugs), and a high price tag. The association of high clinical uncertainty and moderate effect sizes is not surprising in small target populations but in combination with high prices creates the risk of allocative and technical inefficiencies for payers. We here discuss and illustrate these risks. A combination of policies is needed for mitigation of allocative inefficiency: while there may be a rationale for higher prices for orphan than non-orphan drugs, a focus of pricing and reimbursement negotiations should include considerations of product profitability and of the consequences of orphan drug costs on the distribution inequality of medication costs for individual insured persons, coupled to knowledge generation from reimbursement contracts covering high-price orphan drugs that would benefit the wider patient community. Performance-based managed entry agreements could help to de-risk the economic consequences of clinical uncertainty and to mitigate technical inefficiency.

Evaluation of clinical trials done for orphan drugs versus nonorphan drugs in infectious diseasesan eleven year analysis [2010-2020

The 1983 US Orphan Drug Act provided impetus for the development of new therapies for rare diseases. Several studies focused on the number of orphan designations over time. However, very few focused on clinical trials that lead to their approval, particularly for infectious diseases. All new drug approvals (orphan and non-orphan) by the US Food and Drug Administration (FDA) from January 2010 to December 31, 2020, were identified and details of approvals were taken from the US-FDA labels and summary reports for each drug. The pivotal trials for each were characterized based on their design. We tested the association of the type of drug approval with respect to the characteristics of trial using Chi-square test and generated crude odds ratios with 95% confidence intervals. From the total 1122 drugs approved, 84 were for infectious diseases, of which 18 were orphan drugs and 66 were nonorphan. A total of 35 pivotal trials supported 18 orphan drug approvals, while 115 pivotal trials supported 66 nonorphan drugs. The median number of participants enrolled/trial for orphan drugs was 89, while for nonorphan drugs, it was 452 (P < 0.0001). Blinding was done for 13/35 (37%) orphan drugs versus 69/115 (60%) nonorphan drugs (P = 0.029); randomization was done for 15/35 (42%) orphan drugs versus 100/115 (87%) nonorphan drugs (P < 0.0001) and 20/35 (57%) of the orphan drugs got approval in phase II versus 8/115 (6%) of nonorphan drugs (P < 0.00001). A significant number of orphan drugs get approval based on early phase, nonrandomized, and unblinded with a smaller sample size as compared to nonorphan drugs.

HTA46 Outcomes of Benefit Assessments of Orphan Drugs Without Orphan Designation in Germany

Orphan drugs with orphan designation (OD) are granted an added benefit by law in the German HTA process. However, some drugs indicated for rare diseases do not obtain or lose OD, leading to regular benefit assessments without orphan privilege. The objective of the current study is to investigate the outcomes of benefit assessments of orphan drugs without OD in Germany compared to non-orphan drugs and orphan drugs with OD.

The actual status of drug prices and adjustment factors for drug price calculation: an analysis of ultra-orphan drug development in Japan

BackgroundExtremely high prices facilitate drug development for ultra-rare diseases (ultra-orphan drugs). However, various problems arise in terms of healthcare financing and fairness, and the status of ultra-orphan drug pricing remains ambiguous. In this study, we investigated ultra-orphan drug prices in Japan relative to that of other drugs. We examined the relationship between annual expected drug prices and expected sales, and the expected number of patients, for 393 drugs containing new active ingredients for therapeutic use that were listed on the National Health Insurance drug price list in Japan between April 16, 2010 and August 26, 2020. In addition, we compared prices, the drug price calculation method, and price calculation adjustment factors for ultra-orphan and other drugs.ResultsDrug prices tended to increase as the expected number of patients to whom the drug was administered decreased; however, this trend diminished when the expected number of patients was less than 1000. On the other hand, the expected sales tended to decrease as the number of expected patients decreased, and this tendency was reinforced when the expected number of patients was less than 1000. The cost accounting method tended to be used for the price calculation of ultra-orphan drugs, but there were no price differences based on the drug price calculation method. Regarding the price calculation adjustment factors, the premium for usefulness tended to be higher for ultra-orphan drugs. The premium for marketability was higher for non-orphan drugs but did not differ from that for orphan drugs, except for ultra-orphan drugs.ConclusionsThe status of drug prices and expected sales differed beyond a threshold of 1000 expected patients, indicating that recovering the development cost for ultra-orphan drugs is difficult. In addition, the higher premium for usefulness for ultra-orphan drugs reflects the largely unmet need of the associated diseases. Scarcity among orphan drugs is not considered for marketability, highlighting the need for a new framework to promote the development of ultra-orphan drugs.

Pricing and reimbursement policy for new orphan drugs in South Korea: focused on patient accessibility and budget impact

ABSTRACT Background This study aims to analyze the policy and its effects as they apply to new orphan drug (OD) and the budget impact after reimbursement listing in South Korean National Health Insurance (NHI). Methods We analyzed 198 new drugs listed by South Korea’s NHI from July 2007 to March 2017. A comparison of the time to listing for ODs and non-orphan drugs (NODs) was conducted via the Mann–Whitney U test. The budget impact of ODs was analyzed by the NHI claim data from the listing date of new drugs until 31 December 2018. Results An analysis of the time shows that the period (median) for NOD (13.2 months) was shorter than for OD (17.4 months) (Mann–Whitney U test: p = 0.018). The annualized budget impact of OD was 4,967,049 US$/year and that of NOD was 7,800,924 US$/year. Additionally, the percentage of oncology orphan drugs in the total pharmaceutical expenditure was 1.1%; as such, the percentage of non-oncology orphan drug was only 0.9%. Conclusions There has been no significant evidence for patient accessibility improvement regarding new ODs. The proportion of ODs in South Korea’s NHI total pharmaceutical expenditure is not high and the proportion of ODs among new drugs is even lower.

Clinical pharmacology information in regulatory submissions and labeling: A comparative analysis of orphan and non-orphan drugs approved by the FDA.

Clinical pharmacology is an integral discipline supporting the development, regulatory evaluation, and clinical use of drugs for the treatment of both common and rare diseases. Here, we evaluated the recommendations and information available from select clinical pharmacology studies in the therapeutic product labeling of new molecular entities (NMEs) approved from 2017 to 2019 for both common and rare diseases. A total of 151 NMEs, including 72 orphan and 79 non-orphan drugs, were analyzed for recommendations and information available related to food-drug interaction, drug-drug interaction, renal impairment, hepatic impairment, QT assessment, and human radiolabeled mass balance studies using data collected from the original labeling and other regulatory documents. The analysis showed no statistically significant difference in the recommendations between orphan and non-orphan drugs except for renal impairment related recommendations in section 8 of the labeling. Although not significant, fewer hepatic impairment labeling recommendations were available for orphan drugs when compared with non-orphan drugs. At the time of initial approval, 79 postmarketing requirements (PMRs) and postmarketing commitments (PMCs) for 33 orphan drugs and 39 PMRs and PMCs for 19 non-orphan drugs were established; with most difference observed for drug-drug interaction, hepatic impairment, and QT assessment. Overall, although there was a trend for more labeling recommendations and fewer postmarketing studies and clinical trials for non-orphan drugs, there appeared to be no substantial differences in how these select clinical pharmacology studies are leveraged during the development and approval of orphan and non-orphan drugs.

Drug Lag and Associated Factors for Approved Drugs in Korea Compared with the United States.

(1) Background: Drug lag, the delay between the first global regulatory approval and approval by the national health authorities in other countries, impacts the accessibility of drugs. Although the Korean pharmaceutical market has grown significantly, most of its innovative drugs for public health depend on imports from foreign pharmaceutical markets. (2) Methods: We extracted data from the official websites of the Korean Ministry of Food and Drug Safety (MFDS) and the US Food and Drug Administration. Information on new molecule entity drugs, approved as imported drugs by MFDS from 2000 to 2019, was extracted. Multivariate Cox proportional hazard models on drug approval were estimated. (3) Results: In total, 424 drugs were analyzed. Orphan drugs designated by MFDS were less likely to receive approval (HR = 0.731, 95% CI: 0.572–0.934). The drugs with Korean MAHs were less likely to obtain drug approval than those with MAHs of subsidiaries of multinational pharmaceutical companies (HR = 0.524, 95% CI: 0.371–0.738). In the analyses for non-orphan drugs (n = 37), oncology drugs that need local clinical study (HR = 0.247, 95% CI: 0.093–0.657) and drugs that need more patients in a local clinical study (HR = 0.993, 95% CI: 0.988–0.999) were less likely to receive approval, with longer drug lag. The higher number of clinical studies in Korea was associated with a shorter drug lag (HR = 2.133, 95% CI: 1.196–3.805). (4) Conclusions: Our findings imply that Korean pharmaceutical companies should augment their research capabilities for new drug development. Furthermore, consideration of orphan drugs used in rare diseases is needed for drug approval to ensure the availability of these drugs in the market without approval delays.

POSB270 Does Orphan Drug Status Confer Any Benefits for Products Undergoing HTA Appraisal By NICE in England?

Orphan drug status is granted for medicines proposing to target rare diseases with a high level of unmet need, offering incentives for such products. Health Technology Assessment (HTA) agencies will often consider orphan status during their assessments. The purpose of this study is to compare the assessments of orphan and non-orphan drugs by the National Institute of Health and Care Excellence (NICE) since 2018 and determine if orphan status confers any benefit. Single Technology Appraisals and Highly Specialised Technologies published by NICE between January 2018 and June 2021 were identified. For each appraisal, data were extracted on the outcomes, the use of financial agreements and the time from final scope to FAD/FED. The data were analysed to compare the outcomes of orphan and non-orphan drugs. 163 STAs were identified, of which 22% were orphan drugs. A further 8 HSTs (100% orphan drug status) were identified. The overall STA success rate was 90.8%, with no significant difference between the orphan (90.6%) and non-orphan (91.4%) group. In contrast, the HST success rate was 100%. Orphan drugs were more likely to require a financial agreement: 87% STAs and 87.5% HSTs had one, compared to 77% of non-orphan drugs. The timelines for orphan drugs also took ∼10% longer on average, 412 days for STAs and 542 days for HSTs, with non-orphan drugs taking an average of 369 days. Orphan drug status does not confer any benefit during a NICE assessment. The STAs of orphan and non-orphan drugs have a comparable success rate, and orphan drugs are more likely to require a financial agreement and take longer to be assessed. The 100% success rate of HSTs is an exception, but with so few orphan drugs meeting the strict criteria for the HST process, it is a small one.