The fight against the growing Ebola epidemic seems to illustrate a regulatory paradox that may complicate FDA and sponsors’ efforts to encourage drug development for emerging diseases.

While the Ebola treatments in development could qualify for a number of orphan drug incentives, a vaccine for the disease likely would not except in special cases.

The difference between the two seems logical given the interpretation of the legal requirements governing rare disease incentives, but may force some companies away from developing a vaccine, which could prove just as important as a treatment for the disease.

World governments are working feverishly to not only prevent the spread of Ebola, but also to develop treatments and vaccines for the virus.

Attention has grown as cases have been diagnosed in the U.S., including a physician in New York who had just returned from treating patients in Guinea, according to multiple reports. NIH also announced Oct. 24 that Nina Pham, the Dallas nurse treated for Ebola at its clinical center, has been discharged and is virus free.

FDA is one of several agencies working on the U.S. response in an effort to streamline the clinical trial and approval processes for Ebola products ([A#14141016005]).

Among the incentives that may be used is the exclusivity provided through the Orphan Drug Act. Ebola is in fact a rare disease because of its very low incidence rate in the U.S.

FDA Commissioner Margaret Hamburg said Oct. 22 during the National Organization for Rare Disorders’ Rare Diseases and Orphan Products Breakthrough Summit that Mapp Biopharmaceutical Inc.’s ZMapp already has gained an orphan product designation. If approved, it could receive seven years of marketing exclusivity, as well as other incentives.

FDA also could employ its flexibility in efficacy standards for approval of orphan products. FDA has used some form of flexibility in two-thirds of its non-cancer orphan drug approvals (see related story, Also see "FDA Orphan Approval Flexibility Remains Steady As Pressure Increases" - Pink Sheet, 27 October, 2014.).

“We’re responding as flexibly as we can using mechanisms to enable access to investigational medical products when appropriate after the risks and benefits have been weighed,” Hamburg said.

The European Medicines Agency is encouraging companies developing treatments to apply for its orphan status. In addition, EMA and FDA will consider parallel designations (see related story,[A#00141027003]).

The Ebola threat has also pushed EMA to increase its focus on adaptive licensing to speed up approvals of treatments and vaccines Also see "Ebola Threat Prompts EU To Focus On Adaptive Licensing" - Pink Sheet, 16 October, 2014..

FDA hopes its orphan designation will spur further development. But Hamburg and Gayatri Rao, the director of FDA’s Office of Orphan Products Development, both said during the conference an Ebola vaccine likely would not qualify for the same incentive.

Rao said when it comes to judging whether a vaccine gains orphan drug incentives, rather than looking at the incidence of Ebola, the agency considers how many people would be given the vaccine. She concluded it likely would be many more than the 200,000 person threshold that treatments must be under for the designation.

“We would look at who the vaccine would be administered to – is it all health care professionals? Is it all those traveling to West Africa? – in which case those numbers would be significantly higher. So they may not qualify,” Rao said.

A vaccine could gain an orphan designation if its toxicity profile is such that it can only be used by a certain subpopulation of patients, Rao said.

Vaccine Development Continues

Several manufacturers are advancing Ebola vaccine candidates, including one developed by NIH and GlaxoSmithKline PLC. Another vaccine being developed by Profectus BioSciences Inc. received $5.8 million for toxicology studies from the HHS Office of the Assistant Secretary for Preparedness and Response. Janssen Pharmaceutical Cos. also is fast-tracking a combination vaccine with Bavarian Nordic A.S. Also see "“More Is Better” Says J&J As It Takes Up The Ebola Challenge" - In Vivo, 22 October, 2014..

NIH also said Oct. 22 that a Phase I trial for a vaccine developed in Canada and licensed to NewLink Genetics Corp. has started.

NIH already has said clinical trials for an Ebola vaccine would not be conventional in order to make the product available faster ([A#14140916009]).

Orphan incentives certainly would be only one of a number of FDA and government incentives that could encourage development of an Ebola vaccine.

A vaccine also would have a much larger market for potential sales than a treatment, meaning an extended exclusivity inducement may not be as important.

In addition, the European Commission may consider indemnifying sponsors from losses if treatments or vaccines are unsuccessful, according to multiple published reports.

Drug-resistant infections, a sector that has seen development problems in recent years, also have been largely shut out of orphan incentives. FDA has been worried in part that companies would target antibiotics at small populations, knowing that once approved they likely would be used by a much larger group of patients.

A proposal to allow special labeling designating certain new antibiotics for small populations was one idea thought to potentially open the drugs to the incentive Also see "Orphan Antibiotics? Woodcock Says It May Be Possible If IDSA’s New Pathway Is Implemented" - Pink Sheet, 31 March, 2012..

Ebola As Springboard For Broader Reform?

Meanwhile, a company CEO wants to use the alternative ideas and regulatory flexibility employed in the Ebola fight to streamline other drug development efforts.

Robert Hugin, Celgene Corp. chairman and CEO, said during the conference that the Ebola crisis is an opportunity for the rare disease community.

“Why wouldn’t we take the same extraordinary measures to challenge clinical trial strategies, to challenge regulatory requirements, testing requirements for drugs for people that are so, so underserved?” he said. “I think it’s an opportunity for us to reexamine as this crisis we hope fades into control and containment and ultimately a solution.”

Ebola Treatments Could Be Orphan Candidates – But Vaccines, Probably Not

More from Approval Standards

More from Pathways & Standards