Eight Months And Counting: Santen Still Waiting For Final Marketing Decision On Drug Fast-Tracked By EMA
Executive Summary
It has been eight months since the European Medicines Agency recommended market approval for a drug that was reviewed under its fast-track mechanism, but the sponsor has yet to receive a final decision from the European Commission. The company ran into problems when seeking to renew the drug's orphan status before approval.
Not all drugs that are reviewed under the European Medicines Agency’s accelerated assessment pathway go on to receive a timely marketing authorization decision. A case in point is Santen's orphan drug Verkazia (ciclosporin) for treating the rare and severe eye condition vernal keratoconjunctivitis (VKC) in children from four years of age and in adolescents.
Santen’s EU marketing authorization application (MAA) for Verkazia received a positive opinion from the EMA's human medicines scientific committee, the CHMP, in July 2017. However, the European Commission, which issues a legally binding decision on MAAs usually around 67 days after the CHMP adopts an opinion, has still not issued a decision.
Moreover, Santen’s MAA had been reviewed under the EMA’s accelerated assessment process, which is reserved for products deemed by the agency to be of major interest for public health and therapeutic innovation. Accelerated assessments can reduce the review time for MAAs from 210 days (not counting clock stops when applicants must provide additional information) to 150 days.
The delay lies with Santen’s legal obligation to renew Verkazia’s EU orphan designation. At the time of a marketing authorization, orphan drug sponsors must submit an application for the maintenance of the orphan designation in order to be eligible for the 10-year market exclusivity incentive available under the EU Orphan Regulation.
The commission told the Pink Sheet that the delay in Verkazia's case related to the need to renew the drug's orphan status before a marketing authorization decision can be made. The commission said that its decision-making process with respect to Verkazia was still ongoing.
Problems With Renewing The Orphan Status
Verkazia was designated an orphan drug by the EMA's Committee for Orphan Medicinal Products in April 2006. Orphan drugs are eligible for various incentives including free scientific advice on the clinical and non-clinical aspects of the medicine's development.
When the CHMP adopted a positive opinion for Verkazia last July, and recommended that the product be authorized, it clarified that the drug's orphan status would have to be reviewed by the COMP. During the review, the COMP would determine whether, based on the latest information available, the product still met the orphan designation criteria and could, therefore, maintain its orphan status and have access to the 10-year market exclusivity incentive.
The COMP, however, recommended removing Verkazia from the EU Community Register of Orphan Medicinal Products on July 28. Its recommendation was based on its assessment of the therapeutic indication, the prevalence of vernal keratonconjunctivitis, the significant benefit of Verkazia over authorized medicinal products such as anti-histamines and corticosteroids, and magistral/officinal preparation of ciclosporin, the commission explained.
Santen on Oct. 13 appealed against the COMP's recommendation. The COMP on Oct. 30 requested that the company provide the committee with an oral explanation. Following its consideration of the appeal and a request for clarification by the commission, the COMP adopted an opinion in January 2018 confirming its recommendation for the removal of Verkazia's orphan designation.
The commission said it received that COMP’s opinion at the end of January 2018, and that its “decision making process” was still ongoing.
Santen told the Pink Sheet that it does not comment on applications that are under regulatory review. The company said it was "waiting to hear the results regarding ciclosporin 1mg/mL eye drops, emulsion, for the treatment of severe vernal keratoconjunctivitis (VKC) in paediatric populations."
No Significant Benefit
While reviewing Santen’s request for the maintenance of Verkazia's orphan designation, the COMP said the company had failed to demonstrate that the drug would offer a clinically relevant advantage based on better safety, when compared with magistral/officinal formulations.
Santen had argued that there had been a reduction in the production of officinal formulations due to safety concerns associated with manufacturing practices, such as concerns associated with bacterial load and excipients which cause topical irritation. However, this view was not supported by sufficient evidence, the COMP said.
Santen’s assumption that there would be a major contribution to patient care due to improved availability of Verkazia was also rejected by the COMP due to the widespread use of magistral/officinal preparations of ciclosporin in most EU member states. Thus, the assumption that Verkazia may still be of potential significant benefit to those affected by the orphan condition does not hold, the COMP concluded.
From the editors of Scrip Regulatory Affairs.