Generic Biologics Legislation Unlikely, But Issue Not Going Away

The push for legislation creating a follow-on biologics pathway is "cooling off," Senate Aging Committee majority counsel Steve Irizarry told the Stanford Washington Research Group conference in Washington, D.C. May 5.

The recent concerns about drug safety coupled with the European Union's rejection of a follow-on growth hormone application have helped take the steam out of the issue on Capitol Hill, Irizarry said.

"Currently, there is no legislation that has been introduced...nor to my knowledge is there any legislation currently being considered by the Senate Health Committee or the House Commerce Committee," Irizarry noted.

Even proponents of creating a pathway, like Sen. Orrin Hatch (R-Utah), do "not intend to introduce legislation" this year, he said.

One reason there is not much legislative activity involving follow-on biologics, Irizarry said, is "the recent spate of highly publicized drug withdrawals. Of course, I'm referring to not just the COX-2 inhibitors Vioxx and Bextra , but I think more to the point and more relevant to this debate is Tysabri ."

Elan and Biogen Idec suspended the launch of the monoclonal antibody multiple sclerosis therapy Tysabri (natalizumab) on Feb. 28 after reports of fatalities in clinical trials.

In light of the concerns about drug safety, it is hard to push for abbreviated testing procedures for follow-on biologics, Irizarry maintained.

"Those in favor of generic biologics basically say that while their product is not the same as the innovator product, it is similar enough that they should not have to perform the usual battery of clinical tests," he said.

"It is hard to reconcile advocating to the FDA that they need to perform a more rigorous review process for drugs while at the same time proposing a far less strenuous review of a product that arguably presents more of a risk to humans than small molecule drugs."

"You are seeing that drugs that have supposedly gone through the very rigorous rigmarole of FDA approval and yet here they are being withdrawn from the market," he said.

"If that is the case, then it really makes it difficult to argue that on the other hand we should provide less rigorous review for other drugs, particularly biologics which are shown to have a much greater risk than others."

The European Commission's 2004 rejection of Sandoz' growth hormone product Omnitrope also played a role in reducing interest in legislation in the U.S., Irizarry said.

The Novartis subsidiary appeared on the brink of receiving approval under a "biosimilar" process set up by the European Medicines Agency, but the EC declined to license the product under those procedures.

"We don't really know why" the application was rejected "because all of the proceedings are secret," Irizarry noted. "It will be very interesting to see what happens and hopefully get some more information."

Nevertheless, "the European Commission's rejection of Omnitrope really struck a powerful blow to the follow-on biologics movement," Irizarry said. "Looking back on it, it actually played a significant role in the cooling off of this issue on Capitol Hill."

FDA subsequently declined to approve Omnitrope in the U.S., citing the lack of an appropriate regulatory pathway (¹ (Also see "Follow-On And Wait: FDA Defers Action On Sandoz’s Human Growth Hormone" - Pink Sheet, 6 Sep, 2004.), p. 35).

Human growth hormone is one of a handful of biologic products regulated under the FD&C Act and therefore at least theoretically eligible for approval under existing abbreviated pathways in the U.S. (see ² (Also see "USP Human Growth Hormone Monographs Issued; Generics Status Unresolved" - Pink Sheet, 16 May, 2005.)).

However, Irizarry noted, FDA backed away from plans to issue a guidance that would have defined a potential route to approval for those products.

The agency essentially finalized a document in early 2004 but ultimately decided to convene workshops to further define the scientific and regulatory issues rather than formalize a policy (³ (Also see "FDA Follow-On Biologics Background Document To Be Released By Year-End" - Pink Sheet, 1 Nov, 2004.), p. 16).

"Looking back at the reaction from industry and also Congress, FDA's decision to switch to that format was actually not very surprising," Irizarry said.

"Many in Congress, in particular [former Health Committee] Chairman Gregg, made clear to FDA that it was inappropriate to develop a guidance at this time without first receiving express Congressional authorization." Irizarry was previously on the majority staff of the Health Committee under Judd Gregg (R-N.H.).

"The biggest obstacle and the one that really worries industry and even many members of Congress...has to do with trade secrets and proprietary information," Irizarry said.

"Safety and efficacy of biologics is highly dependent on process-specific manufacturing, and without such information, which is protected from disclosure under law, it is impossible to exactly replicate both the process and the product."

"In that sense, it is unclear how FDA would or could approve a follow-on biologic that claims to be the same or similar to an innovator product unless they were actually able to get that trade secret information from the innovator."

Despite the obstacles and the loss of momentum on Capitol Hill, Irizarry believes the pressure for a follow-on biologics pathway is not going away.

In fact, "the pressure to develop a follow-on biologic is only going to increase over time," as biotechnology products consume an ever increasing share of pharmaceutical spending.

"Five years down the road you are finally going to start to have some data as to the cost of the Medicare program," Irizarry noted. "If those costs are through the roof - which I believe they will be - I think you are going to have a serious look at all manner of trying to reduce drug costs."

"I think that you will see the issue of generic biologics come about again."