Exploring the Potential Challenges for Developing Generic Orphan Drugs for Rare Diseases: A Survey of US and European Markets.

The US Food and Drug Administration in 1983 and the European Union's European Medicines Agency in 2000 implemented the orphan drug development program for rare diseases. The study aimed to find the potential challenges encountered by generic companies in developing generics for rare diseases. We performed a thematic analysis, which consists of qualitative and quantitative research. For data analysis of approved orphan drugs, we used statistical methods, and for the industrial case study, we selected 14 generic companies and conducted semistructured interviews related to 10 critical areas of drug development. The orphan drug approvals were classified into 4 categories: the number of orphan approvals, pediatric claims, formulation, and therapeutic areas. We analyzed the approvals from 2001 to 2021; the Food and Drug Administration approved 815 drugs and European Medicines Agency approved 258 drugs. The pediatric orphan approvals were analyzed from 2010 to 2021; the average percentage of orphan drugs claim pediatric exclusivity during this period was found to be 31.8%. In formulation, we found the highest percentage of drugs belong to small molecules at 71%. In the therapeutic class, oncology drugs have a majority of approvals at 25%. The industrial case study responses revealed that the major challenge for drug development is the complexity of the disease at 21%, followed by the limited market at 17%. There is a high need for generic orphan drugs in the developing countries. The generic companies can use the opportunities provided by health authorities for the benefit of both the company and the patient perspective.

Murthannagari VR ，Gonna Nandhi Krishnan G ，Manu KV ，Jayachandraiah CT ，Mandadhi Rajendra PK ，Ahmed SS ... -  《-》

Effective Market Exclusivity of New Molecular Entities for Rare and Non-rare Diseases.

Kerr KW ，Glos LJ 《-》

Market Exclusivity for Drugs with Multiple Orphan Approvals (1983-2017) and Associated Budget Impact in the US.

Padula WV ，Parasrampuria S ，Socal MP ，Conti RM ，Anderson GF ... -  《-》

Ethical imperatives of timely access to orphan drugs: is possible to reconcile economic incentives and patients' health needs?

Rodriguez-Monguio R ，Spargo T ，Seoane-Vazquez E 《Orphanet Journal of Rare Diseases》

Modifying the Criteria for Granting Orphan Drug Market Exclusivity.

To examine policy options to deny orphan drug exclusivity after drugs exceed a target population of 200 000 across all orphan indications (combined prevalence threshold) or once drugs receive a nonorphan approval (market approval threshold). Retrospective analysis of drugs with 2 or more orphan approvals from 1983 to July 01, 2017 examining prevalence of orphan indications and approval years of orphan and nonorphan indications. Characteristics of drugs crossing either threshold are described. A budget impact analysis of Medicare and Marketscan® claims databases estimated potential savings from generic or biosimilar entry as a result of foregone market exclusivity periods determined by these policies. Out of 86 drugs with 2 or more orphan approvals, 21 drugs would be denied orphan drug exclusivity periods under the prevalence threshold and 18 drugs would be denied orphan drug exclusivity periods under the market approval threshold. Drugs with orphan approvals after 2010 were more likely to be denied orphan drug exclusivity. In 2017, Medicare could have saved about $2 billion on 8 drugs under the prevalence threshold policy and $1.3 billion on 12 drugs under the market approval threshold policy). Private insurers could have saved $814 and $919 million, respectively. Over half of the savings would come from 9 drugs that first entered the market for a nonorphan indication. Modifying the criteria for granting orphan drug exclusivity would affect a small number of orphan drugs but could generate large savings through increased competition. Other incentives such as grants or tax credits for clinical trials could be explored to incentivize research for new orphan indications for drugs that crossed either threshold.

Socal MP ，Parasrampuria S ，Anderson GF 《-》