Imiglucerase (Cerezyme)

Imiglucerase is a recombinant enzyme-replacement drug for Gaucher disease, a genetic disorder in which a missing enzyme lets fatty material build up in the liver, spleen, bone marrow and bones. Approved in 1994 as a lab-made successor to an earlier drug purified from human placentas, it became the standard of care worldwide for over a decade — until a 2009 virus contamination shut down its only production plant, triggered a years-long global shortage, drew a $175 million FDA penalty, and reshaped who makes Gaucher disease drugs today.

From human placentas to recombinant cells

Gaucher disease is a rare inherited disorder in which a deficiency of the enzyme glucocerebrosidase (also called acid beta-glucosidase) lets a fatty substance, glucocerebroside, accumulate inside macrophages throughout the body. In its most common form (type 1), that buildup enlarges the liver and spleen, crowds out normal bone marrow function causing anemia and low platelet counts, and damages bone. Before enzyme-replacement therapy existed, the only options were symptomatic — splenectomy, blood transfusions, joint replacement — and did nothing to stop the underlying disease. The first real treatment, alglucerase (Ceredase), was approved by the FDA in April 1991: a genuine breakthrough, but one built on an impractical supply chain, since the enzyme had to be purified and chemically modified from pooled human placental tissue — thousands of placentas were needed to treat a single patient for a year. Genzyme developed a recombinant alternative, imiglucerase, produced in genetically engineered Chinese hamster ovary (CHO) cells rather than human tissue, and the FDA approved it on 23 May 1994 under the brand name Cerezyme.

The trial that let Cerezyme replace Ceredase

Because imiglucerase was intended as a direct, more scalable successor to an already-approved drug rather than a first-in-class treatment, the key evidence was a head-to-head comparison rather than a placebo-controlled trial. A randomized, double-blind, parallel-group trial assigned 30 Gaucher disease patients (15 children and adults on each arm) to receive either Ceredase or Cerezyme, both dosed at 60 U/kg by infusion every two weeks for nine months, and tracked hemoglobin, platelet counts, and liver and spleen volume. The two drugs produced statistically indistinguishable improvements across those measures (Grabowski GA, Barton NW, Pastores G, et al., "Enzyme therapy in type 1 Gaucher disease: comparative efficacy of mannose-terminated glucocerebrosidase from natural and recombinant sources," Ann Intern Med 1995;122(1):33-39, PMID 7985893).¹ That result, together with the practical case for a manufacturing process that did not depend on human placental tissue, supported Cerezyme's approval, and it steadily replaced Ceredase as the standard Gaucher disease treatment worldwide over the following years.

2009: a virus shuts down the only plant that makes it

This was not a finding about whether Cerezyme worked for patients who could get it — it is a manufacturing and supply-chain failure, distinct from the drug's own clinical evidence. But it is a real regulatory story worth being accurate about: a single point of failure at one facility left a population of patients with a serious, progressive disease without reliable access to their only approved treatment for an extended period.

The consent decree, the $175 million, and a change of owner

In May 2010, Genzyme signed a consent decree with the FDA governing the Allston facility, and in November 2010 paid $175 million as a disgorgement of past profits tied to the manufacturing violations — on top of ongoing remediation requirements and third-party oversight of the plant. Genzyme itself changed hands during this period: on 16 February 2011, Sanofi-aventis announced a deal to acquire Genzyme for $74.00 per share in cash, plus a contingent value right tied partly to future Cerezyme and Fabrazyme production milestones, in a transaction valued at roughly $20.1 billion; it closed later that year. Cerezyme has been manufactured and marketed by Sanofi's Genzyme division ever since.

Current status

Imiglucerase remains FDA-approved and marketed today as Cerezyme, and the underlying manufacturing crisis has not recurred. But the shortage had a lasting competitive effect: it created the opening for two newer enzyme-replacement drugs — velaglucerase alfa and taliglucerase alfa, covered on this site's companion page — to reach the market faster than they otherwise would have, and a meaningful share of patients who switched to one of those alternatives during the shortage never switched back once Cerezyme's supply normalized. Cerezyme also now competes with an entirely different, non-infused approach: oral substrate-reduction drugs such as eliglustat (Cerdelga, approved 2014, also marketed by Genzyme/Sanofi), which lower glucocerebroside production instead of replacing the missing enzyme. Patients today have a genuinely wider set of real, approved options than existed before 2009 — a direct, if unintended, consequence of the shortage this page describes.