Genzyme Ready To Launch Fabrazyme And Aldurazyme; User Fee Dates Near

Genzyme is ready to launch both Fabrazyme and Aldurazyme simultaneously if FDA approvals come through in April, the company says.

"We are...preparing to launch these products together," Therapeutics President Christi van Heek told an April 16 analysts conference call.

FDA's user fee deadline for the Fabry's disease therapy Fabrazyme (agalsidase beta) is April 24. Genzyme expects a decision on the mucopolysaccharidosis I agent Aldurazyme (laronidase), developed under a joint venture with Biomarin, by April 30.

Assuming both products are approved, Genzyme will be ready for a simultaneous launch, relying on its platform for the Gaucher's disease therapies Ceredase (aglucerase) and Cerezyme (imiglucerase).

"We are leveraging what we built in the past with Gaucher's disease and now expanding and continuing to build on that," van Heek said.

"The treating physicians are predominantly within the centers of excellence in the U.S." for lysosomal transfer disorders, van Heek noted. "We are also building many satellite centers, referring centers if you will, and infusion centers," she said. "So whether it is a Fabrazyme patient, a Gaucher's patient, or an Aldurazyme patient, we are going to leverage this infrastructure that we have been working on."

The company has been training its Gaucher's sales force for the launches, van Heek added. "We have been working with the payors...doing a lot of focus groups with them and a lot of one-on-one meetings."

Genzyme CEO Henri Termeer advised analysts to consider the company's experience in the Gaucher's market as a model for the long-term prospects of Fabrazyme and Aldurazyme.

The Cerezyme/Ceredase franchise has grown "every year...for now 12 years," Termeer said. "This is very typical of what you can expect of these ultra-orphan diseases. We would expect Fabrazyme also to continue to grow over long periods of time. We would expect the same for Aldurazyme." Sales of Cerezyme were up 13% during the first quarter to $167.2 mil. There are now 3,700 patients worldwide receiving Cerezyme or Ceredase, Genzyme said.

The timing of Genzyme's first quarter conference call made questions about the likelihood of approval for Fabrazyme and Aldurazyme inevitable. During a March conference call, Termeer indicated confidence that Aldurazyme would be approved by the deadline, but less certainty about Fabrazyme (¹ (Also see "Genzyme Revises Fabrazyme Phase IV Proposal In Bid For April Approval" - Pink Sheet, 10 Mar, 2003.), p. 24).

On the April 16 call, Termeer said his assessment of the outlook remains the same.

With just one week remaining for a decision on Fabrazyme, it may be interpreted as a positive sign that Genzyme still sees approval as a possibility.

"We feel very good about the discussions we've had with the agency" about Fabrazyme, Termeer said. "We believe that approval can take place while maintaining the integrity of the currently ongoing Phase IV trial, and we will wait to see how the FDA will act on April 24."

[Editor's Note: Genzyme has previously cited April 23 as the user fee deadline for Fabrazyme. However, Genzyme said that date was off by one day, due to an "error" in FDA's calculation.]

"It is tricky of course at this moment to make a precise prediction" of how the agency will respond, Termeer added.

The "primary" focus of discussions over Fabrazyme has been on ensuring that a clinical endpoint trial can be completed if the agent is commercialized. An FDA advisory committee recommended approval of the drug in January, provided the trial's integrity can be protected (² , p. 12).

During the March conference call, Termeer explained that Genzyme has modified its proposal to capture data from the study if the placebo arm is lost. He suggested that the proposal was receiving careful consideration at FDA, raising the chances for approval on the user fee date. The alternative, Genzyme believes, is approval in December or January, once the pivotal study is essentially complete.

Termeer was asked whether FDA has raised the possibility of granting approval on the condition that Genzyme agree not to launch until the pivotal trial wraps up. "I think that there are probably a thousand such variations that one could think of," Termeer said, "and it really is not very helpful to discuss many of these here...so I'm not going to."

Approval of Fabrazyme would secure orphan drug exclusivity for the Genzyme product, blocking TKT's agalsidase product Replagal . The TKT agent was not recommended for approval by the advisory committee (³ (Also see "TKT Replagal Surrogate Data Should Be Reworked For Accelerated Approval" - Pink Sheet, 20 Jan, 2003.), p. 14).

One factor in FDA's decision on Fabrazyme is the likelihood that the orphan drug race could lead to litigation.

Genzyme wants its claim to orphan exclusivity to be "in as strong a position as possible," Termeer noted. The company is "working very constructively with FDA, making sure that the right conclusions are reached for the right reasons, with very strong data underlying the decisions."

The outcome of the advisory committee reviews of the Fabry's products may already be paying off for Genzyme.

Both Fabrazyme and Replagal are already on the market in Europe. During the quarter, Genzyme saw 15 switches of patients from Replagal to Fabrazyme. The company has not seen any recent switches in the opposite direction.

Genzyme estimates that there are close to 600 patients on therapy in Europe, with approximately 350 receiving Fabrazyme (including about 90 in clinical trials).

For Aldurazyme, Termeer was less guarded in his optimism. "The regulatory work that is going on between Biomarin and FDA is making tremendous progress."

Biomarin has "submitted information related to post-marketing commitments and product labeling that the agency requested in its complete response letter of Jan. 28," Genzyme said. "In addition, the inspection process for the Aldurazyme manufacturing facility has been completed."

The two companies "recently established a global patient registry as part of broad-ranging preparations in anticipation of product launch."

Termeer noted that post-marketing studies for Aldurazyme will be "in the commercialized setting," with patients enrolled followed "on particular criteria more intensely."