Orphan Drug Research Articles

HPR56 Rare Disease Policies and Orphan Drug Designation Processes in European and Asia-Pacific (APAC) Countries

HPR56 Rare Disease Policies and Orphan Drug Designation Processes in European and Asia-Pacific (APAC) Countries

HPR188 Orphan Drugs – How Will the New Proposed European Union (EU) Commission Pharmaceutical Regulation Impact Therapies for Rare Diseases?

HPR188 Orphan Drugs – How Will the New Proposed European Union (EU) Commission Pharmaceutical Regulation Impact Therapies for Rare Diseases?

HTA320 Predicting Value and Price of Orphan Drugs: A Comparison Across Europe and the US

HTA320 Predicting Value and Price of Orphan Drugs: A Comparison Across Europe and the US

HTA321 Factors Influencing the Shi Costs of Orphan Drugs After Their Renewed Regular Benefit Assessment Due to Exceeding the Sales Threshold in Germany

HTA321 Factors Influencing the Shi Costs of Orphan Drugs After Their Renewed Regular Benefit Assessment Due to Exceeding the Sales Threshold in Germany

HPR100 Orphan Drugs in Algeria and Six Other Countries: A Cross Comparison Study

HPR100 Orphan Drugs in Algeria and Six Other Countries: A Cross Comparison Study

HTA175 The Impact of Accelerated Regulatory Approval on Health Technology Assessment: An Evaluation of Orphan Drugs in Four Markets

HTA175 The Impact of Accelerated Regulatory Approval on Health Technology Assessment: An Evaluation of Orphan Drugs in Four Markets

HTA108 Willingness-to-Pay for Orphan Drugs – ICER Thresholds Approved by TLV in Sweden

HTA108 Willingness-to-Pay for Orphan Drugs – ICER Thresholds Approved by TLV in Sweden

HTA29 Analysis of the Change of the Added Benefit and Respective Reasons in Renewed Regular Benefit Assessments of Orphan Drugs Due to Exceeding the Sales Threshold in Germany

HTA29 Analysis of the Change of the Added Benefit and Respective Reasons in Renewed Regular Benefit Assessments of Orphan Drugs Due to Exceeding the Sales Threshold in Germany

HPR102 Factors Influencing Orphan Drug Net Prices in the EU4 and US – Insights from Payers

HPR102 Factors Influencing Orphan Drug Net Prices in the EU4 and US – Insights from Payers

HPR29 Evolution of the Utilization of the Aifa 5% Fund for Orphan Drugs and Rare Diseases

HPR29 Evolution of the Utilization of the Aifa 5% Fund for Orphan Drugs and Rare Diseases

EE394 Understanding Reasons of Negative Reimbursement Decisions for Orphan Drugs in the Spanish National Health System (APRIL 2019-MAY 2023)

EE394 Understanding Reasons of Negative Reimbursement Decisions for Orphan Drugs in the Spanish National Health System (APRIL 2019-MAY 2023)

EE248 Evolution in Price Levels of Orphan Medicinal Products (OMP): Looking Back at the Past Decade

EE248 Evolution in Price Levels of Orphan Medicinal Products (OMP): Looking Back at the Past Decade

Trofinetide in Rett syndrome: A brief review of safety and efficacy.

Rett syndrome (RTT) is a rare genetic neurological disorder that primarily affects girls and is caused by mainly mutations in the methyl-CpG-binding protein 2 (MECP2) gene, leading to critical issues in normal brain function. The condition has a global prevalence of 5 to 10 cases per 100,000 females, and there is currently no cure for RTT. However, therapy is available to manage the symptoms and improve quality of life. Trofinetide, an insulin-like growth factor 1, was originally developed as a stroke medication and progressed to Phase II clinical trials, where it exhibited favorable safety and efficacy profiles by improving several core RTT symptoms. Recently, Trofinetide received the US Food and Drug Administration (FDA) approval and orphan drug designation for the treatment of RTT, making it the first approved drug for this rare genetic disorder. It has also shown to be safe, well-tolerated and with no known drug interactions. These findings suggest that Trofinetide is a promising treatment option for individuals with RTT.

Vosoritide, a miracle drug, covering unmet need in achondroplasia: A regulatory update.

Dwarfism is a rare condition characterized by small stature. Achondroplasia is predominantly considered the leading cause of dwarfism. Although the condition is not life-threatening, it dramatically impacts the social life of the patient. The United States Food and Drug Administration (US FDA) first approved the drug Voxzogo (vosoritide) for achondroplasia. The drug also received approval from the European Medicines Agency (EMA) via the centralized procedure. The drug is associated with a decrease in blood pressure, a severe adverse event. However, this adverse event/risk has been overcome by benefits, i.e. fulfilling of unmet medical need. In the United States, the drug received accelerated approval as it satisfied the criteria of rare pediatric disease. This review includes a detailed orphan drug approval process with particular reference to vosoritide, which is considered a milestone for the treatment of achondroplasia.

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.

Approval Delay in Drugs from Non-Global Company in Europe and Japan: Analysis of Novel Drugs for Hematologic Malignancies

Background: Since most therapeutic agents for hematologic malignancies are developed and first approved in the US, it is important for each country to review and approve these agents without delay. Recently, the number of drugs developed by non-global companies including biotech start-ups has increased. Most of these non-global companies are located in the US, and typically do not have offices outside of the US. Thus, it is possible that drugs developed by non-global companies are likely to be approved later in countries other than the US, including the EU. However, their characteristics have not been fully evaluated. Study Design and Methods: Using the public database of the Food and Drug Administration (FDA) from January 2011 to December 2020, new molecular entity (NME) drugs for hematological malignancies that were approved in the US during the relevant period were identified. Cellular products, including chimeric antigen receptor (CAR)-T cells, were excluded from this analysis. NMEs for hematological malignancies were divided into two categories according to the applicant company: NMEs from non-global companies (non-Global group) and NMEs from global companies (Global group). Global companies were defined as those with branches or headquarters in all following regions: the US, the EU, and Japan. The others were classified as non-global companies. Based on the public databases of Japanese regulatory agency (PMDA) and European regulatory agency (EMA), we estimated the rate at which these drugs remained unapproved (unapproved rate) using the Kaplan-Meier method. The unapproved rate of NMEs was compared between the non-Global and Global groups. Results: A total of 39 NMEs for hematologic malignancies approved in the US during the study period were identified. Of these, 13 (33%) NMEs were from non-global companies (non-Global group) and 26 (67%) NMEs were from global companies (Global group). The proportion of orphan drug (13/13 vs. 26/26, p=1.000) and priority review designation (12/13 [92%] vs. 22/26 [85%], p=0.648) were not significantly different between the non-Global and Global groups. In the non-Global group, 12 (92%) NMEs were from the companies headquartered in the US, while 10 (39%) NMEs were from the US companies in the Global group. The proportion of pivotal phase Ⅰ/Ⅱ trial used for marketing authorization in the US was significantly higher in the non-Global group (11/13 [85%] vs. 13/26 [50%], p=0.045). The proportion of pivotal trials enrolling Japanese participants was lower in the non-Global group (0/13) than in the Global group (6/26 [23%]), while the proportion was similar in the EU (9/13 [69%] in the non-Global group and 16/26 [62%] in the Global group). In the EU, the unapproved rate 2 years after the US approval was higher in the non-Global group (54% vs. 22%), but the 5-year unapproved rate was rather lower than that in the Global group (15% vs. 22%) (Figure 1a). Similarly, in Japan, the unapproved rate of NMEs in the non-Global group was higher at 2 years (92% vs. 65%), but rather slightly lower than that in the Global group at 5 years (20% vs. 35%) (Figure 1b). After the US approval, 9 (69%) of the 13 NMEs filed by non-global companies had subsequently partnered with or been acquired by the global companies. Discussion and Conclusion: In both the EU and Japan, drugs in the non-Global group had a higher unapproved rate at 2 years. Notably, 54% of the drugs in the non-Global group were not approved in the EU, even though the participation rate in the pivotal trial used for US approval was similar between the non-Global and Global groups in the EU. However, at 5 years, the unapproved rate had decreased to approximately 20% in both the EU and Japan, presumably due to the fact that lots of the non-global companies were subsequently partnered with or acquired by the global companies.

Cost of Exempting Sole Orphan Drugs From Medicare Negotiation

The Inflation Reduction Act (IRA) requires Medicare to negotiate prices for some high-spending drugs but exempts drugs approved solely for the treatment of a single rare disease. To estimate Medicare spending and global revenues for drugs that might have been exempt from negotiation from 2012 to 2021. This cross-sectional study analyzed drugs that met the IRA threshold for price negotiation (Medicare spending >$200 million/y) in any year from 2012 to 2021 and had an Orphan Drug Act designation. We stratified drugs into 4 mutually exclusive categories: approved for a single rare disease (sole orphan), approved for multiple rare diseases (multiorphan), initially approved for a rare disease and subsequently approved for a nonrare disease (orphan first), and initially approved for a nonrare disease and subsequently approved for a rare disease (non-orphan first). The primary outcomes were the number of sole orphan drugs, estimated Medicare spending on those drugs from 2012 to 2021, and global revenue since launch. Among 282 drugs, 95 (34%) were approved to treat at least 1 rare disease, including 25 sole orphan drugs (26%), 20 multiorphan drugs (21%), 13 orphan first drugs (14%), and 37 non-orphan first drugs (39%). From 2012 to 2021, Medicare spending on sole orphan drugs increased from $3.4 billion to $10.0 billion. Each year, a median (IQR) of $2.5 ($1.9-$2.6) billion in Medicare spending would have been excluded from price negotiation because of the sole orphan exemption. The cumulative global revenue of the median (IQR) sole orphan drug was $11 ($6.6-$19.2) billion. The sole orphan exemption will exclude billions of dollars of Medicare drug spending from price negotiation. The high level of global revenues achieved by these drugs, however, suggests that special exemption is unnecessary for them to achieve financial success. Congress could consider removing the sole orphan exemption to obtain additional savings for patients and taxpayers and to eliminate any potential disincentive for developing additional indications for these drugs.

Prevalence and nature of manufacturer-sponsored patient support programs for prescription drugs in Canada: a cross-sectional study.

Globally, pharmaceutical companies offer patient support programs in tandem with their products, which aim to enhance medication adherence and patient experience through education, training, support and financial assistance. We sought to identify the proportion and characteristics of such patient support programs in Canada and to describe the nature of supports provided. We conducted a crosssectional study to identify and characterize all marketed prescription drugs available in Canada as of Aug. 23, 2022, using the Health Canada Drug Product and CompuScript databases. To describe the nature of supports provided, we conducted a content analysis of publicly available patient support program websites and Web-based documents. Using logistic regression, we identified characteristics of drugs associated with having a patient support program including brand-name or branded generic (generic medications with a proprietary name), orphan (medications for rare diseases) or biologic drug status; estimated total cost of prescriptions dispensed at retail pharmacies; and price per unit. Of the 2556 prescription drugs marketed by 89 companies in the study period, 256 (10.0%) had a patient support program in Canada. Many of the 89 drug manufacturers (n = 55, 61.8%) offered at least 1 patient support program, frequently relying on third-party administrators for delivery. Brandname and branded generic medications, biologic agents and drugs with orphan status were more likely to have a patient support program than generic drugs. Compared with drugs priced $1.01-$10.00 per unit, drugs priced $10.01-$100.00 per unit were nearly 8 times more likely to have a patient support program (adjusted odds ratio 7.54, 95% confidence interval 4.07- 14.64). Most sampled patient support programs included reimbursement navigation (n = 231, 90.2%) and clinical case management (n = 223, 87.1%). About 1 in 10 drugs marketed in Canada has a manufacturersponsored patient support program, but these are concentrated around brand-name, branded generic, biologic and high-cost drugs, often for rare diseases. To understand the impact of patient support programs on health outcomes and sustainable access to cost-effective medicines, greater transparency and independent evaluation of patient support programs is necessary.

Analysis of the provisions of national and EAEU legislation regulating pharmaceuticals before and after 1 January 2026

Scientific relevance. The gradual transition to the common pharmaceutical market within the Eurasian Economic Union (EAEU) is expected to be completed by the end of 2025, and a new regulatory framework is currently being developed at both the national and supranational levels. The main changes in Russian national legislation are aimed to harmonise it with EAEU legislation. However, Russian national legislation will continue regulating a range of issues related to the life cycle of medicines.Aim. This study aimed to compare the Russian and EAEU legal frameworks regulating medicines before and after January 2026, as well as to analyse the risks of conflicts of laws between these legal systems.Discussion. Analysing the causes of potential conflicts of laws between Russian and EAEU legislation, the authors consider solutions for such conflicts outlined in the legal system of the Russian Federation, as well as the applicability of these solutions to specific situations in the national and supranational regulation of medicines. This study analyses the stages in the life cycle of medicines associated with the highest risk of conflicts of laws, including clinical trials, the development of pharmacopoeial requirements, and the designation of orphan medicines. The authors examine the relationships between authorisation procedures during the transition period with both legal systems in effect. The analysis highlights the issues that will continue to be regulated under Russian national legislation after the completion of the transition period, such as the inclusion of active substances in the Russian State Register of Medicines, the authorisation of medicines during armed conflicts or other emergencies, and the interchangeability of medicines. Given the evolving requirements of the regulatory environment, this study provides suggestions for enhancing the regulatory framework and recommendations for applicants.Conclusions. After the complete transition to the common market in the EAEU, certain requirements of Russian Federal Law No. 61-FZ “On Circulation of Medicines” of 12 April 2010 will remain effective in the Russian Federation. Therefore, during the transition period, applicants for authorisation should consider the partial continuation of national regulation after 2026 when developing their regulatory affairs strategies.

Investigation of the diagnostic importance and accuracy of CT in the chest compared to the RT-PCR test for suspected COVID-19 patients in Jordan

This article aims to synthesize the existing literature on the implementation of public policies to incentivize the development of treatments for rare diseases, (diseases with very low prevalence and therefore with low commercial interest) otherwise known as orphan drugs. The implementation of these incentives in the United States (US), Japan, and in the European Union (EU) seems to be related to a substantial increase in treatments for these diseases, and has influenced the way the pharmaceutical research & development (R&D) system operates beyond this policy area. Despite the success of the Orphan Drug model, the academic literature also highlights the negative implications that these public policies have on affordability and access to orphan drugs, as well as on the prioritization of certain disease rare areas over others. The synthesis focuses mostly on the United States’ Orphan Drug Act (ODA) as a model for subsequent policies in other regions and countries. It starts with a historical overview of the creation of the term “rare diseases”, continues with a summary of the evidence available on the US ODA’s positive and negative impacts, and provides a summary of the different proposals to reform these incentives in light of the negative outcomes described. Finally, it describes some key aspects of the Japanese and European policies, as well as some of the challenges captured in the literature related to their impact in Low- and Middle-Income Countries (LMICs).