Berinert and Cinryze

Berinert and Cinryze are the two original, plasma-derived C1 esterase inhibitor (C1-INH) replacement drugs for hereditary angioedema — purified directly from pooled human donor plasma, approved a year apart for opposite purposes: Berinert (2009) for treating an attack already underway, Cinryze (2008) for routine prophylaxis to prevent attacks before they start. Both predate, and set up the comparison for, this site's Conestat Alfa page, which covers the newer recombinant, rabbit-milk-derived alternative to both.

The originals, replacing the protein itself

Hereditary angioedema (HAE) is usually caused by a deficiency or dysfunction of C1 esterase inhibitor (C1-INH), a protein that normally restrains the kallikrein-bradykinin pathway; without enough working C1-INH, bradykinin builds up and causes sudden, painful swelling attacks. This site's icatibant and ecallantide pages cover drugs that work further downstream in that pathway. Berinert and Cinryze take the most direct route: they replace the missing or malfunctioning C1-INH protein itself, purified directly from pooled human donor plasma. They were the first two C1-INH replacement products approved in the US, arriving a year apart for two different jobs — Cinryze first, for prevention, then Berinert, for treating an attack once it starts.

Berinert: acute attacks, and the IMPACT trial

CSL Behring's Berinert was approved by the FDA on 9 October 2009 for treating acute abdominal and facial HAE attacks in adults and adolescents, based on the IMPACT1 trial: a randomized, double-blind, placebo-controlled study in 125 patients comparing Berinert at 10 U/kg or 20 U/kg against placebo. At the approved 20 U/kg dose, the median time to onset of symptom relief was 0.5 hours, versus 1.5 hours on placebo — a statistically significant difference (p=0.0025) that was even larger for severe attacks specifically (Craig TJ et al., J Allergy Clin Immunol 2009;124(4):801-808, PMID 19767078). The label was expanded in January 2012 to cover self-administration and treatment of laryngeal attacks, the most dangerous kind, based on further open-label data (the I.M.P.A.C.T.2 extension study, PMID 21884533).

Cinryze: prophylaxis, and the trial that ran both directions at once

Cinryze — then developed by Lev Pharmaceuticals — was approved by the FDA on 10 October 2008 for routine prophylaxis against HAE attacks, the first C1-INH product approved in the US for that preventive use rather than for treating an attack in progress. The pivotal evidence was a placebo-controlled crossover trial in 22 patients, comparing twice-weekly 1,000-unit Cinryze injections against placebo across two 12-week periods: patients had a mean of 6.26 attacks per 12 weeks on Cinryze versus 12.73 on placebo, roughly halving attack frequency, with the milder and shorter attacks that did occur. A companion study in the same publication tested Cinryze for acute attacks instead — a different, non-prophylactic use — finding a median time to relief of 2 hours versus more than 4 hours on placebo (both studies: Zuraw BL et al., N Engl J Med 2010;363(6):513-522, PMID 20818886). Cinryze's approved US label covers only the prophylaxis use; the acute-treatment data in that same paper did not itself become a separate approved indication for the drug.

Ownership and manufacturing, not a safety story

Cinryze changed hands repeatedly after approval: ViroPharma acquired Lev Pharmaceuticals in 2008, Shire acquired ViroPharma for roughly $4.2 billion in a deal that closed 24 January 2014, and Shire itself became part of Takeda when that company completed its $62 billion acquisition of Shire on 8 January 2019. In 2017, a shortage at Cinryze's Dutch contract manufacturer (Sanquin) disrupted supply, prompting Shire to transfer some production to its own Vienna, Austria facility — a real operational disruption worth naming plainly, but a manufacturing and business story, not a finding about the drug's efficacy or its approved safety profile. Berinert, by contrast, has stayed with a single manufacturer (CSL Behring) throughout its US history.

Current status

Both remain FDA-approved and currently marketed: Cinryze by Takeda for prophylaxis, Berinert by CSL Behring for acute attacks. CSL Behring later added a third plasma-derived option, Haegarda, approved 22 June 2017 as the first subcutaneous C1-INH for prophylaxis — its Phase 3 COMPACT trial found a 95% reduction in the median number of attacks at the approved 60 IU/kg dose compared with placebo. All three sit alongside the newer recombinant Conestat Alfa as approved options along the same replacement-therapy approach, distributed only through specialty pharmacies to diagnosed HAE patients — not a drug class with any presence among "research chemical" grey-market vendors.