FDA's decree that Myozyme made by Genzyme for Pompe's disease at the 160-liter bioreactor scale is a different product from the same drug made at the 2,000-liter scale means a delay in approval of the latter, as the firm puts together a separate BLA.

That's the bad news.

The good news for Cambridge, Mass.-based Genzyme is that the firm had planned to submit results from the Late-Onset Treatment Study (LOTS) with the drug as post-marketing data by May 31 anyway.

FDA is "willing to have a form of a rolling BLA," with the regulatory clock starting as soon the agency has the LOTS data in hand, said Alison Lawton, Genzyme's senior vice president of regulatory affairs, during an April 21 conference call.

For makers of biosimilars, the news may not be so great, either. As shown by Myozyme's latest hurdle, FDA has "set a high bar" for such products, Lawton said.

Oppenheimer analyst Brian Abrahams had written in an April 15 research note that FDA's blessing for the 2,000-liter Myozyme plant was "probable near term, and likely already included in most Street estimates," though a delay "would not be impossible given the current regulatory environment."

It happened. Genzyme now expects a decision on the 2,000-liter scale Myozyme (alglucosidase alpha) by the end of the year. In the meantime, the delay hits the firm's top line to the tune of about $45 million, taking away 10 cents earnings per share.

"We are not changing in any way the outlook into the future," said Henri Termeer, chairman, president and CEO, repeating the vow of 20 percent compound average growth rate yearly through 2011.

"The LOTS trial was initiated a long time ago, and that's why we can file [the new BLA] so quickly," Termeer added.

FDA distinguished the two Myozymes from each other because of slight carbohydrate differences, though Lawton said regulators "made it very clear that they wanted to be able to use all of the review they've done to date" when considering the new BLA.

"Basically, we will plan to cross reference everything back to the 160-liter BLA," with LOTS the most important piece of the new filing, she said. "That, if you like, will be the pivotal study for approval of the 2,000-liter [BLA]."

Termeer summed up the situation.

"The way this stacks up in the very short run in the U.S., we will have two approved products for Pompe's disease - one for small scale and one for large scale [production]," he said.

It's not efficient, but Termeer said he expects the situation to be temporary.

Myozyme is already approved in the U.S. at the 160-liter scale. David Meeker, president of lysosomal storage disorder therapeutics for Genzyme, said he is "extremely confident" in the drug's safety and efficacy.

"We're finishing the first quarter with more than 900 patients on therapy," he said. The drug won clearance from FDA in April 2006 (¹ Also see "Myozyme Is First FDA-Approved Inherited Muscle Disorder Therapy" - Pink Sheet, 1 May, 2006.).

More than 800 patients have been treated with 2,000-liter material. Patients on 160-liter material have been switched to 2,000-liter, and vice versa, Meeker said.

To make certain that adults with Pompe's disease get the drug in the U.S., Genzyme with the FDA created Myozyme Temporary Access Program (MTAP) in May 2007, which is now treating about 140 patients.

But too few adults were transitioned into MTAP to guarantee the remaining infants, children and adults would have a steady supply of Myozyme until larger-scale manufacturing is cleared by FDA.

MTAP will quit enrolling, Termeer said, until Genzyme and the agency determine a better way forward.

In Europe, Myozyme made at the 2,000-liter level is the only approved drug. Genzyme is working on a 4,000-liter plant in Belgium.

Genzyme will report first-quarter earnings April 23.

- Randall Osborne (r.osborne@elsevier.com)

FDA To Genzyme: Another Myozyme BLA, Please

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