Genzyme Says Work At Allston Plant Will Resume As Planned Later This Month

Viral contamination in one of the plant's bioreactors caused a complete shutdown, stopping new production of Cerezyme and Fabrazyme.

Genzyme will restart operations at its Allston Landing, Mass., plant next week, resuming the production of orphan drugs Cerezyme and Fabrazyme . However, during its second-quarter 2009 earnings call on July 22, the biotech conceded that supplies of those two drugs probably won't be available until November or December.

At the time Genzyme shut down the plant in mid-June, the biotech explained that Vesivirus 2117 was found in material used to make Cerezyme, raising concerns about quality control. But the biotech pledged the site would return to operation before the end of July, a goal that Genzyme execs were quick to note is being met (Also see "Genzyme Plant Cleanup Brings Temporary Halt To Fabrazyme, Cerezyme Production" - Pink Sheet, 16 Jun, 2009.). Just the same, it remains unclear how the virus found its way into the plant.

The episode prompted so many unanswered questions that, in recent weeks, there was growing industry speculation that Genzyme would not be able to meet its schedule. This intensified after the FDA invited two companies developing experimental drugs for Gaucher disease to file treatment INDs, which are intended to bring those drugs to market more quickly. Cerezyme (imiglucerase) is the only drug currently approved for Gaucher.

Some industry watchers took FDA's call to Shire - to accelerate development of human cell-produced velaglucerase - and to Protalix - to speed up its work on plant-cell expressed recombinant glucocerebrosidase - as an indication the agency believed Cerezyme shortages may be worse than Genzyme originally projected ( (Also see "Shortage Could Cause Early Access To Developmental Gaucher Disease Drugs" - Pink Sheet, 13 Jul, 2009.), p. 23).

The biotech makes Cerezyme and Fabrazyme only at the Allston facility and in June warned that Cerezyme shortages would be felt in August and that Fabrazyme shortages would be noticeable in September or October. To address the problem, Genzyme developed dose-reduction recommendations with the FDA and the European Medicines Agency for both drugs.

In Europe and the U.S., stable adult Gaucher patients have been asked to cut their Cerezyme doses in half in order to preserve existing supplies for more vulnerable populations, including children with the lysosomal storage disorder. U.S. patients taking Fabrazyme, which treats Fabry disease, have been asked to skip two doses between July 1 and Sept. 30, while in Europe, a reduced dose has been recommended for female patients.

Allston site will be dedicated solely to Cerezyme, Fabrazyme

Genzyme did not have large stockpiles of the two drugs on hand at the time of the shutdown because it also was using the Allston site to make the 2,000 liter formulation of Pompe disease drug Myozyme .

When the Allston plant goes back into production, chief executive Henri Termeer told analysts that all six bioreactors will be dedicated solely to making Cerezyme and Fabrazyme, while all Myozyme production will take place at a 4,000 liter facility in Belgium. Myozyme produced on the 4,000 liter scale has been approved by EMEA, but still awaits FDA approval.

Genzyme said the shutdown cost $13 million in Cerezyme revenue during the second quarter. For the full year, the biotech has reduced its sales guidance for the drug significantly - the original $1.25 billion to $1.275 billion range being cut to between $750 million and $1 billion.

In a July 22 note, J.P. Morgan analyst Geoff Meacham called this guidance "worse than expected" and noted the company also lowered its total revenue guidance for the year from a range of $5.15 billion to $5.35 billion, to a range of $4.6 billion to $5 billion.

According to David Meeker, Genzyme's executive vice president for genetic diseases, biosurgery and transplant, the broad range in guidance reflects the still unanswered question of how much "work in progress" Cerezyme material can be completed and sold. The lower end of the guidance reflects the possibility that no work-in-progress material will be deemed usable by regulators.

This is not a factor for Fabrazyme because viral contamination was not found in the bioreactors used to make that drug, according to Genzyme execs, who noted there was no work-in-progress material available at the time of the shutdown.

In a supply update shortly after the Allston plant shutdown, Genzyme reported that Vesivirus 2117 was not detected in any released lots of Cerezyme and the virus has not been shown to cause health problems in humans. The virus can interfere with the growth of Chinese hamster ovary cells that Genzyme uses to make Cerezyme, Fabrazyme and Myozyme.

PCR assay unable to detect source of virus

To bring the facility back online, all six bioreactors were "pulled apart and sanitized top to bottom," Termeer said. Genzyme says it also is using an enhanced polymerase chain reaction assay to test the bioreactors for viral content, a process that will continue during drug manufacturing.

Despite these efforts, Meeker said that PCR testing to date has not revealed the source of the virus. But Genzyme is still rebuilding the bioreactors, which will be inoculated next week, he said.

To reach and maintain needed levels of both drugs next year, Genzyme decided it has to dedicate the Allston plant entirely to the production of Cerezyme and Fabrazyme, according to Geoff McDonough, senior vice president. Genzyme also has accelerated construction of a second plant to make the two drugs in Framingham, Mass., and expects FDA approval of that facility in 2011.

"We will need the Allston plant throughout next year, and the recovery is not that quick," McDonough said. "We need full production ... we clearly need safety inventories into the system throughout the world."

Reflecting the fact that it no longer makes the 2,000 liter formulation of Myozyme at Allston, Genzyme has decided to stop making that formulation entirely, even though its BLA is pending at FDA. The drug currently is approved in the U.S. at the 160 liter production scale.

The PDUFA date for the 2,000 liter application is Nov. 14. Genzyme's strategy, assuming it gains approval, is to follow FDA's okay with an immediate supplemental BLA for the 4,000 liter formulation, which it believes FDA could review within four months. That would mean Myozyme made at the firm's Belgian facility could win U.S. approval by March 2010.

-Joseph Haas ([email protected])