Eculizumab & Ravulizumab (Soliris & Ultomiris)

Eculizumab is the original antibody drug this site's own pegcetacoplan and zilucoplan pages already reference as the comparator: the first monoclonal antibody ever approved to block complement protein C5, cleared by the FDA in March 2007 for a rare blood disease and since expanded, indication by indication, to three more. Ravulizumab is Alexion's own engineered successor — same target, same company, four amino-acid substitutions that stretch its dosing interval from every two weeks to every eight. Between them they built a genuine regulatory and legal record beyond the drug itself: a decade-plus run as the world's most expensive medicine, an SEC bribery settlement, a $125 million investor settlement, and — after 17 years of exclusivity — the first biosimilar competition in 2024.

The first antibody built to block C5

Eculizumab is a humanized monoclonal antibody, developed by Alexion Pharmaceuticals, that binds complement protein C5 and blocks it from being cleaved into C5a and C5b — the same terminal step in the complement cascade this site's pegcetacoplan page (acting further upstream, at C3) and zilucoplan page (a small peptide hitting the identical C5 target) both describe. Eculizumab got there first, and by a wide margin: the FDA approved it, as Soliris, on 16 March 2007 for paroxysmal nocturnal hemoglobinuria (PNH), a rare disorder in which uncontrolled complement activity destroys red blood cells — the first approved treatment of any kind for that disease. The pivotal TRIUMPH trial randomized 87 transfusion-dependent PNH patients to eculizumab or placebo for 26 weeks; the median transfusion requirement fell from 10 units per patient on placebo to 0 on eculizumab, and 49% of eculizumab patients achieved hemoglobin stabilization versus 0% on placebo (Hillmen P, Young NS, Schubert J, et al., "Effect of Eculizumab on Hemolysis and Transfusion Requirements in Patients with Paroxysmal Nocturnal Hemoglobinuria," N Engl J Med 2006;355(12):1233-1243, PMID 16990386, DOI: 10.1056/NEJMoa061648).¹

From one rare blood disease to four separate diseases

Eculizumab's label grew through three further approvals over the following twelve years, each in an unrelated disease sharing only the same complement-driven mechanism. In September 2011 the FDA granted accelerated approval for atypical hemolytic uremic syndrome (aHUS) — a genetic disease causing complement-driven blood-clot formation in small vessels — on the strength of two prospective, open-label Phase 2 trials totaling 37 adult and adolescent patients (17 in one trial, 20 in the other) plus a retrospective pediatric case series; the full trial results, later published, found eculizumab produced a rapid, sustained hematologic response, with 82% of patients in the acute-TMA trial reaching a normal platelet count by week 26 (Legendre CM, Licht C, Muus P, et al., "Terminal Complement Inhibitor Eculizumab in Atypical Hemolytic-Uremic Syndrome," N Engl J Med 2013;368(23):2169-2181, PMID 23738544, DOI: 10.1056/NEJMoa1208981).² On 23 October 2017, eculizumab became the first new FDA-approved treatment for generalized myasthenia gravis (gMG) in more than sixty years, based on the Phase 3 REGAIN trial: 125 anti-acetylcholine-receptor-antibody-positive patients randomized to eculizumab or placebo for 26 weeks, with a statistically significant improvement on the MG-Activities of Daily Living scale (Howard JF Jr, Utsugisawa K, Benatar M, et al., "Safety and efficacy of eculizumab in anti-acetylcholine receptor antibody-positive refractory generalised myasthenia gravis (REGAIN): a phase 3, randomised, double-blind, placebo-controlled, multicentre study," Lancet Neurol 2017;16(12):976-986, PMID 29165251, DOI: 10.1016/S1474-4422(17)30369-1).³ On 27 June 2019, it became the first approved drug for anti-aquaporin-4 (AQP4) antibody-positive neuromyelitis optica spectrum disorder (NMOSD), a rare autoimmune disease of the central nervous system: the Phase 3 PREVENT trial found a relapse in just 3% of eculizumab-treated patients versus 43% on placebo over 48 weeks — a 94% reduction in relapse risk (Pittock SJ, Berthele A, Fujihara K, et al., "Eculizumab in Aquaporin-4-Positive Neuromyelitis Optica Spectrum Disorder," N Engl J Med 2019;381(7):614-625, PMID 31050279, DOI: 10.1056/NEJMoa1900866).⁴

Ravulizumab: the same target, engineered for far fewer infusions

Eculizumab's biggest practical burden is its dosing schedule: an IV infusion at a clinic every two weeks, indefinitely, after an initial once-weekly loading phase. Ravulizumab is Alexion's own answer to that problem — not a new drug target, but the identical anti-C5 antibody re-engineered with four amino-acid substitutions (two that make its C5 binding pH-dependent, two in the Fc region that improve recycling through the neonatal Fc receptor back into circulation instead of being degraded), extending its half-life to roughly four times eculizumab's. That lets ravulizumab be dosed by IV infusion every 8 weeks instead of every 2, after a single loading dose — cutting a patient's infusions from about 26 a year to about 6 or 7. Two head-to-head, active-controlled Phase 3 trials backed its first approval (as Ultomiris, 21 December 2018, for PNH): the "301" study randomized 246 complement-inhibitor-naive PNH patients to ravulizumab or eculizumab and found ravulizumab noninferior on transfusion avoidance and LDH normalization (Lee JW, Sicre de Fontbrune F, Wong Lee L, et al., "Ravulizumab (ALXN1210) vs eculizumab in adult patients with PNH naive to complement inhibitors: the 301 study," Blood 2019;133(6):530-539, PMID 30510080, DOI: 10.1182/blood-2018-09-876136);⁵ the "302" study found the same noninferiority in 195 patients already stable on eculizumab who switched to ravulizumab (Kulasekararaj AG, Hill A, Rottinghaus ST, et al., "Ravulizumab (ALXN1210) vs eculizumab in C5-inhibitor-experienced adult patients with PNH: the 302 study," Blood 2019;133(6):540-549, PMID 30510079, DOI: 10.1182/blood-2018-09-876805).⁵ Ravulizumab went on to pick up the same three further indications as eculizumab — aHUS (18 October 2019), gMG (28 April 2022, on the Phase 3 CHAMPION-MG trial's 175 patients), and NMOSD (25 March 2024, the first long-acting C5 inhibitor approved for that disease) — effectively replacing eculizumab as Alexion's lead product across the same four-disease franchise.

A famous price, and a real legal record to go with it

AstraZeneca announced its acquisition of Alexion in December 2020 and completed the roughly $39 billion deal on 21 July 2021, making Soliris and Ultomiris AstraZeneca-subsidiary products. That didn't end the drug's legal history: on 16 April 2025, health insurer EmblemHealth filed a proposed antitrust class action in the US District Court for the District of Massachusetts alleging AstraZeneca/Alexion obtained additional patents on Soliris after its original patents were due to expire in 2021, delaying biosimilar entry through what the complaint calls "sham" patent litigation against would-be competitors, and estimating resulting US purchaser overpayments at more than $2 billion. The presiding judge has since dismissed the complaint's claim that the patents themselves were fraudulently obtained, while allowing the separate sham-litigation claim to proceed — an unresolved allegation, not a court finding of liability, as of this review.

Biosimilars arrive, 17 years later

Soliris's original patent protection ran out around 2021, but the first actual biosimilar competition didn't reach the US market until 2024 — the gap the 2025 antitrust suit above puts at the center of its complaint. On 28 May 2024 the FDA approved Bkemv (eculizumab-aeeb, Amgen), the first interchangeable biosimilar to Soliris, for PNH and aHUS; on 19 July 2024 it approved a second, Epysqli (eculizumab-aagh, Samsung Bioepis), also interchangeable and cleared across all four of Soliris's indications. Ravulizumab, protected by its own separate, later patent estate, has no biosimilar competition as of this review. Both eculizumab and ravulizumab remain in active clinical use across PNH, aHUS, gMG and NMOSD, prescribed and monitored by treating specialists under REMS-mandated meningococcal vaccination — with no wellness, off-label or grey-market interest of any kind, the same pattern this site's other complement-inhibitor pages describe.