Rare disease advocates are wondering whether it may be time to strengthen the Orphan Drug Act and at least one organization is researching potential improvements that could be made to the pathway.

The talk is not surprising, given that negotiations to reauthorize the Prescription Drug User Fee Act are nearing completion. Incentives or other changes for drugs targeting rare diseases could be packaged with the reauthorization bill.

It also is likely some proposed changes may target patient costs for the drugs. Rare disease advocates believe already high prescription costs may be growing out of control.

Peter Saltonstall, CEO of the National Organization for Rare Disorders, said Feb. 28 the group is developing priorities for how to improve the Orphan Drug Act, which was enacted in 1983.

Saltonstall said NORD will issue a position soon on whether any “improved incentives” are needed.

Last year the biggest structural challenge to the Orphan Drug Act in its 28-year history emerged. The biosimilars approval pathway, created as part of the Affordable Care Act, offers innovator biologics 12 years of exclusivity, dwarfing the seven years given to orphan products as a formal development incentive from the government.

“NORD is actually working with a group of board members and outside individuals looking at [whether] is it time to think about enhancing the orphan drug act in some way,” Saltonstall said during Rare Disease Day activities at the National Institutes of Health. “I don’t have the answer to that right now. We’re having meetings. We’re talking about it.”

Orphan drugs are increasingly popular, especially among large pharma companies, because of the available incentives. That was the intent of the act, which offers seven years of marketing exclusivity for successful approvals.

The Pharmaceutical Research and Manufacturers of America reported last month 460 rare disease drugs are in the late stages of the development pipeline. The largest number target cancer, followed by genetic and neurological disorders.

Orphan designations, a precursor to marketing approval that qualifies the sponsor for incentives, reached an all-time high of 192 in 2010, according to Christine Mueller, a medical officer in the Office of Orphan Products Development. FDA has issued 35 designations so far this year, according to agency information.

The new popularity already appears to have consequences for rare disease patients. Saltonstall said the escalating cost of rare disease drugs is a particular problem. Insurance companies are beginning to refuse off-label uses as the number of large pharma companies in the space increases, he said.

It appeared from his comments that suggested improvements to the act may include ideas for cost control.

“It’s important for us to make sure that we make the pathway as attractive as we can without being abused,” Saltonstall said. “I have to say to you that some of the costs of some of the drugs ... I recognize that [companies] have to have a return on investment, but let’s try to figure out how to do it in a more equitable fashion.”

NORD's target date to issue its position is unclear, except that it is coming “in the near future.” The group said it could be released fairly soon if PDUFA was to be involved.

Legislation May Be In The Works Already

Meanwhile, Congress already could be working on potential changes.

A Senate staffer recently said legislation was expected in the near future addressing rare diseases. The staffer said there has been a lot of discussion about how to incentivize rare disease drug development and senators are interested in the issue.

Questions include how the legislation would be structured. It could be modeled after the Orphan Drug Act or be introduced as an amendment, the staffer said.

The House of Representatives relaunched the Rare Disease Congressional Caucus on Feb.28, but the group has not taken any formal policy positions. A spokesman for caucus member Rep. Robert Dold, R-Ill., said no Orphan Drug Act changes had been discussed as of the kick-off meeting.

Changes also could come packaged in the PDUFA reauthorization and rare disease issues already are set to be included in the FDA-industry agreement.

Both sides have agreed on a proposal to allow user fee revenue to add agency staff to CDER and CBER to focus on rare disease development, according to minutes of a Jan. 10 negotiation.

The proposal also includes guidance and policy development and outreach to patient organizations about drug development and a public meeting to talk about clinical trial issues (Also see "PDUFA V Agreement Set In Four Areas, But Broad FDA/Industry Talks Continue" - Pink Sheet, 7 March, 2011.).

The agency also has announced a training schedule to help staff better understand rare disease issues (Also see "FDA To Offer Reviewers Rare Disease Training; Patient Groups Want Separate ODE" - Pink Sheet, 6 December, 2010.).

Orphan Scientific Requirements To Change?

The agency also could adjust its pre-approval requirements for orphan applications. At a March 2 meeting, FDA’s Advisory Committee for Pharmaceutical Science and Clinical Pharmacology offered recommendations on how the agency could increase its flexibility in pre-approval data requirements for orphan drugs.

The meeting follows the agency’s efforts to boost orphan drug development, but also indicates concern about approving drugs with minimal safety data (see Also see "Orphan Drugs Warrant Flexibility On Clinical Pharmacology Data, FDA Panel Says" - Pink Sheet, 21 March, 2011.).

Rare disease advocates have been arguing the agency needs to relax its policies in order to spur more rare disease drug development.

NORD and others continue to ask FDA to allow the use of biomarkers and surrogate endpoints to grow the development pipeline.

They also said the classic double-blind, placebo-controlled clinical trial may not be the only design the agency should accept (Also see "Orphan Drug Reviews: Industry Wants FDA To Move Out Of Its Comfort Zone" - Pink Sheet, 5 July, 2010.).

By Derrick Gingery

Does The Orphan Drug Act Need A Facelift? Advocates Consider Changes

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