Velaglucerase Alfa and Taliglucerase Alfa (VPRIV and Elelyso)

Velaglucerase alfa and taliglucerase alfa are two separate enzyme-replacement drugs for Gaucher disease, developed by two different companies, that reached the market faster than they otherwise would have because of the 2009-2012 shortage of imiglucerase (Cerezyme) described on this site's companion page. Each has its own real placebo- or active-comparator-controlled trial evidence, and each uses a genuinely different, non-animal manufacturing method than the CHO-cell process behind Cerezyme — one grown in a human cell line, the other the first plant-cell-expressed drug the FDA had ever approved.

Two drugs whose timing owes something to another drug's shortage

This site's imiglucerase page covers the 2009 viral contamination that shut down the only plant manufacturing Cerezyme, the sole enzyme-replacement therapy for Gaucher disease at the time, and the resulting shortage that left patients rationed or without treatment into 2010 and beyond. Two other companies already had competing Gaucher disease enzymes in development when that shortage hit, and both received an FDA Priority Review — an expedited timeline reserved for drugs addressing a serious unmet need — with the ongoing Cerezyme shortage cited at the time as part of the urgency. Neither drug was invented because of the shortage; both had it not existed, would very likely have reached the market on a normal timeline. But the shortage measurably compressed how fast patients could get access to a genuine alternative.

VPRIV: a human cell line, reviewed on an expedited track

Shire's velaglucerase alfa is produced in a human cell line (HT-1080, a fibrosarcoma-derived line engineered to secrete the enzyme) rather than the Chinese hamster ovary cells used for imiglucerase — a manufacturing choice intended to produce a glycosylation pattern closer to the natural human enzyme. The FDA approved it on 26 February 2010, under Priority Review, for adults and children with type 1 Gaucher disease; contemporaneous coverage of the approval explicitly noted the ongoing Cerezyme shortage as context for why a fast review mattered. The supporting evidence included an open-label Phase 1/2 study and extension (Zimran A, Loveday K, Fratazzi C, Elstein D, "Phase 1/2 and extension study of velaglucerase alfa replacement therapy in adults with type 1 Gaucher disease: 48-month experience," Blood 2010;115(23):4651-4656, PMID 20299511)¹ and a randomized, double-blind, dose-comparison Phase 3 trial in 25 treatment-naive patients, which found significant improvements in hemoglobin, platelet counts and spleen volume at both tested doses over 12 months (Gonzalez DE, Turkia HB, Lukina EA, et al., "Enzyme replacement therapy with velaglucerase alfa in Gaucher disease: results from a randomized, double-blind, multinational, Phase 3 study," Am J Hematol 2013;88(3):166-171, PMID 23386328).² Because approval came quickly, the evidence most relevant to the shortage itself — how patients already stable on imiglucerase did after being switched to velaglucerase alfa — was only published afterward: an open-label study of Gaucher disease type 1 patients transitioned from imiglucerase found hemoglobin, platelet counts and organ volumes remained stable through 12 months on the new drug (Zimran A, Pastores GM, Tylki-Szymanska A, Hughes DA, Elstein D, et al., "Safety and efficacy of velaglucerase alfa in Gaucher disease type 1 patients previously treated with imiglucerase," Am J Hematol 2013;88(3):172-178, PMID 23339116).³

Elelyso: the first plant-cell-expressed drug the FDA had approved

Taliglucerase alfa, developed by the Israeli biotech Protalix BioTherapeutics and marketed in partnership with Pfizer as Elelyso, took a still more unusual manufacturing route: it is expressed in genetically engineered carrot plant cells grown in disposable bioreactors (Protalix's ProCellEx platform), rather than any mammalian cell line at all. The FDA approved it on 1 May 2012 — the first plant-cell-expressed recombinant protein drug the agency had ever approved, a genuine manufacturing first rather than a marketing claim. The pivotal evidence was a randomized, double-blind, dose-comparison Phase 3 trial in 31 treatment-naive adults with type 1 Gaucher disease, comparing 30 U/kg and 60 U/kg doses every two weeks over nine months; both doses met the primary endpoint of a statistically significant reduction in spleen volume, with corresponding improvements in hemoglobin and platelet counts (Zimran A, Brill-Almon E, Chertkoff R, et al., "Pivotal trial with plant cell-expressed recombinant glucocerebrosidase, taliglucerase alfa, a novel enzyme replacement therapy for Gaucher disease," Blood 2011;118(22):5767-5773, PMID 21900191, DOI: 10.1182/blood-2011-07-366955).⁴

What the shortage changed, and what stuck

During 2009-2012, a substantial number of Gaucher disease patients who had been stable on imiglucerase were switched — some more than once — to whichever alternative enzyme-replacement therapy had supply available, out of medical necessity rather than a head-to-head preference. Once Cerezyme's own supply normalized in 2012, imiglucerase did not regain the position it had held before the shortage: both VPRIV and Elelyso retained meaningful shares of the treated Gaucher disease population, a pattern company financial disclosures and trade press have both described as a lasting effect of the shortage rather than a temporary bridge. This is a genuinely unusual outcome for a drug shortage — the disruption outlasted the supply problem that caused it, because it gave patients and physicians real, working alternatives they had reason to stay on.

Current status

Both drugs remain FDA-approved and currently marketed. VPRIV is marketed by Takeda, which acquired Shire in a deal completed 8 January 2019 (the same acquisition that brought Cinryze under Takeda, as described on this site's Berinert & Cinryze page). Elelyso continues to be marketed by Pfizer under its manufacturing and commercialization agreement with Protalix. Together with imiglucerase and the oral substrate-reduction drugs eliglustat and miglustat, Gaucher disease patients today have a genuinely wider set of approved treatment options than existed before 2009 — an indirect but real legacy of the manufacturing crisis that briefly left the disease with only one approved treatment at all.