Complete response letter and warning notice regarding production plant were issued.
Genzyme received notices from the FDA detailing further requirements before Lumizyme™ can be approved for the treatment of Pompe disease. The agency’s complete response letter asks for more details on the planned postapproval studies. A warning letter was also issued regarding deficiencies at the manufacturing facility.
Severely affected adults with Pompe disease in the U.S. already have access to Lumizyme under the Myozyme Temporary Access Program (MTAP), which was established with the FDA in May 2007. Myozyme contains the same active ingredient but is produced in a 160 L bioreactor. Since this limits supply, the drug has marketing approval for infants and children.
Assuming a six-month delay, Genzyme anticipates the impact on 2009 non-GAAP earnings will be approximately $0.12 per share. This reflects both foregone commercial sales margin and the costs of continued administration of the MTAP program. Genzyme now expects Myozyme revenue of $370 to $380 million in 2009, down from $430 to $440 million as was previously expected.
The warning letter was issued as a result of FDA’s visit to Genzyme’s 2,000 L bioreactor that produces Lumizyme in September and October 2008. It noted problems related to aspects of microbiological monitoring and controls, production equipment maintenance, and certain process controls.
Genzyme reports that it initially responded to the agency on October 31, 2008, with a detailed plan and timeline to address all its concerns. The company adds that it provided a progress update on February 23 confirming that all corrective actions had either been completed or were on schedule to be completed by the original commitment date of March 31. Thus Genzyme was surprised to receive this warning letter.
The complete response letter noted that Genzyme and the FDA must finalize the design of a postapproval verification study to demonstrate the clinical benefit of Lumizyme, as required under the accelerated approval process. In addition, Genzyme and the agency need to finalize the risk evaluation and mitigation strategy.
Genzyme believes that all the information requested by the agency is readily at hand and that the company will be able to submit this information within approximately one month.
The company also plans to submit an sBLA for 4,000 L scale production during the first half. Myozyme produced at the 2,000 L scale has been sanctioned for use in all patients with Pompe disease in more than 40 countries including those in the EU.