FDA Analyst Counters Critiques of Orphan Drug Act

Regulatory NewsRegulatory News | 18 October 2017 |  By 

While recent reports have claimed that drugmakers are manipulating the incentives provided by the Orphan Drug Act, Mike Lanthier, an operations research analyst at the US Food and Drug Administration (FDA), says that in most cases, the act is working as intended.

"My sense is that the Orphan Drug Act has been a successful catalyst for spurring rare disease development," Lanthier said at the National Organization for Rare Disorders' (NORD) Summit in Washington, DC on Tuesday.


Congress passed the Orphan Drug Act in 1983 to incentivize the development of drugs to treat rare diseases by offering drugmakers tax credits, fee waivers and a seven-year period of marketing exclusivity for an approved orphan indication. To qualify for orphan drug designation, a product must be intended to treat a disease that affects fewer than 200,000 people in the US, or more than 200,000 if the drugmaker can show that it is not expected to recoup its costs to develop and market the drug.

Critics of the act claim it has allowed drugmakers to charge exorbitant prices for many orphan drugs and argue that drugmakers have taken advantage of its incentives by repurposing existing drugs to treat rare diseases or getting approval of a drug in multiple subtypes of a disease, a practice known as salami-slicing.

According to FDA, only 10 treatments for rare diseases were developed in the decade leading up to the Orphan Drug Act. Another estimate finds that 34 drugs that would have qualified for orphan drug designation were approved between 1967 and 1983.

Between 1983 and 2016, FDA approved 451 orphan drugs for 590 rare disease indications. It is estimated that there are some 7,000 rare diseases, most of which have no approved treatments.


According to Lanthier, the vast majority of those drugs (374, 83%) were initially approved for orphan indications and only 12% were first approved to treat a common condition before being approved for an orphan indication.

Lanthier then said he wanted to find out whether companies are "getting orphan approval at the outset … just to get their foot in the door to add non-rare indications later on."

Based on his analysis, three quarters of the 374 drugs that were first approved as orphan products were never approved for an additional indication. Another 11% were approved for additional indications within the same disease as the initial approval, such as the addition of a pediatric indication.

Only 8% of the drugs were approved for indications in other rare diseases and only 7% were later expanded for use in a non-orphan indication.

"Most drugs that encounter the Orphan Drug Act start out as a rare disease treatment and throughout their marketing history actually remain rare disease treatments," Lanthier said.

He also addressed the fact that many of the top-selling drugs on the market have been approved for orphan indications.

"One of the things that's been pointed out by people is that there are a lot of high revenue drugs on the market—some of the top selling drugs—have at least one orphan indication approved," Lanthier said.

To examine the issue more closely, Lanthier looked at the 20 top selling drugs of 2016 based on data from QuintilesIMS. While eight of those drugs had at least one orphan indication, only three were approved first as orphan drugs before being expanded to a more common indication.

Lanthier also said that these top-selling drugs are somewhat atypical with regard to how many indications they've been approved for, as six of the eight drugs had between 6 and 15 approved indications. Of the remaining two drugs, Copaxone (glatiramer acetate) was only approved for a single indication and Neulasta (pegfilgrastim) was approved for a single orphan indication following its initial approval.

"The sheer number of indications approved in these products is unusual, they've expanded their indications in multiple ways, including multiple indications for non-rare indications, which probably accounts for a lot of the revenue that's being generated by these drugs," Lanthier said.

He also pointed to the number of orphan products qualifying for FDA's expedited review programs as evidence that orphan drugs often have the potential to bring a meaningful benefit to patients.

"The high proportion of these approvals that are qualifying for FDA's priority review and breakthrough therapy designation suggests a need or potential of orphan drugs to have a positive impact on the rare diseases they treat," Lanthier said.


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