Ravulizumab

Structural formula
	No drawing available
General
Non-proprietary name	Ravulizumab
other names	ALXN1210
Molecular formula	C 6430 H 9888 N 1696 O 2028 S 48
External identifiers / databases
DrugBank	DB11580
Wikidata	Q55641547
Drug information
ATC code	L04 AA43
Drug class	Monoclonal antibody
Mechanism of action	Selective immunosuppression
properties
Molar mass	about 148 kD
safety instructions
	Please note the exemption from the labeling requirement for drugs, medical devices, cosmetics, food and animal feed
GHS hazard labeling ; no classification available
	As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Ravulizumab (trade name Ultomiris ; manufacturer Alexion ) is a drug from the group of monoclonal antibodies that is used in the treatment of paroxysmal nocturnal hemoglobinuria (PNH). The mode of action is based on the binding to the complement component C5 . This inhibits their splitting and reduces hemolysis (destruction of red blood cells). Ravulizumab was approved in the US in December 2018 and in the EU in July 2019.

properties

Biological and chemical properties

Ravulizumab is a recombinant humanized IgG _{2 / 4κ monoclonal} antibody that consists of two identical heavy chains of 448 amino acids and two identical light chains of 214 amino acids that are linked by disulfide bonds .

It is produced using recombinant DNA technology in cell cultures from ovarian cells of the Chinese hamster ( Chinese Hamster Ovary, CHO ).

Pharmacological properties

Ravulizumab binds to complement component C5 , which subsequently blocks complement- mediated intravascular hemolysis.

The substance is considered to be a further development of the drug eculizumab , from which it differs in four places by deviations in the amino acid sequence in the heavy chain. This modification favors the dissociation of the ravulizumab: C5 complex in the endosome , so that after the free antibody has been returned to the vascular compartment, its availability there is increased. This increase in the antibody half-life allows for less frequent administration compared to eculizumab.

Therapeutic steady-state drug concentrations (equilibrium concentrations) are reached after the first dose. Ravulizumab has a mean terminal elimination half-life of 49.7 days, which is three to four times longer than that of eculizumab (11.3 days). Ravulizumab therefore only needs to be administered every eight weeks, whereas eculizumab every two weeks. For the patients, the number of infusions drops from 26 to 6 per year.

Clinical information

application areas

Ravulizumab is indicated for the treatment of adult PNH patients with haemolysis and clinical symptoms suggestive of high disease activity, as well as in patients who are clinically stable after being treated with eculizumab for at least the previous six months.

The recommended dose of ravulizumab is based on the patient's body weight. Ravulizumab is given intravenously as an infusion.

Contraindications

Ravulizumab should not be given at

Hypersensitivity to the active substance,
Patients with uncured meningococcal infection (Neisseria meningitidis) at the start of treatment.
Patients without current vaccination against meningococci (Neisseria meningitidis), unless they are receiving appropriate antibiotic prophylaxis for up to two weeks after vaccination.

unwanted effects

The most common possible side effects are upper respiratory tract infections , inflammation of the lining of the nose and throat (nasopharyngitis) and headache. The most serious side effects in patients in clinical trials are meningococcal infection and meningococcal sepsis .

Therapy costs

In Germany, the annual therapy costs for the statutory health insurance (GKV) amount to 413,373.73 euros per patient (7 treatments of 3.27 mg based on a patient's average body weight of 77 kilograms; as of 2019).

Individual evidence

↑ This substance has either not yet been classified with regard to its hazardousness or a reliable and citable source has not yet been found.
↑ ^a ^b ^c ^d EMA: Summary of Product Characteristics. (PDF) Retrieved May 11, 2020 .
↑ McKeage K: Ravulizumab: First Global Approval. In: Drugs . tape 79 , no. 3 , February 2019, p. 347–352 , doi : 10.1007 / s40265-019-01068-2 (English).
↑ Austin G. Kulasekararaj et al .: Ravulizumab (ALXN1210) vs eculizumab in C5-inhibitor – experienced adult patients with PNH: the 302 study . In: Blood . tape 133 , 2019, pp. 540-549 , doi : 10.1182 / blood-2018-09-876805 .
↑ German Society for Hematology and Medical Oncology eV (DGHO): Ravulizumab DGHO Statement 2019112. (PDF) Retrieved on May 11, 2020 .
↑ ^a ^b K. Gräfe: New antibody for rare blood disease . In: Pharmaceutical newspaper . 5th September 2019.
↑ G-BA : Dossier on the benefit assessment according to Section 35a SGB V - Ravulizumab (Ultomiris®) from July 25, 2019. Accessed June 4, 2020 . (PDF).

[NV-1] This substance has either not yet been classified with regard to its hazardousness or a reliable and citable source has not yet been found.

[smpc-2] EMA: Summary of Product Characteristics. (PDF) Retrieved May 11, 2020 .

[3] McKeage K: Ravulizumab: First Global Approval. In: Drugs . tape 79 , no. 3 , February 2019, p. 347–352 , doi : 10.1007 / s40265-019-01068-2 (English).

[4] Austin G. Kulasekararaj et al .: Ravulizumab (ALXN1210) vs eculizumab in C5-inhibitor – experienced adult patients with PNH: the 302 study . In: Blood . tape 133 , 2019, pp. 540-549 , doi : 10.1182 / blood-2018-09-876805 .

[5] German Society for Hematology and Medical Oncology eV (DGHO): Ravulizumab DGHO Statement 2019112. (PDF) Retrieved on May 11, 2020 .

[pz2019-6] K. Gräfe: New antibody for rare blood disease . In: Pharmaceutical newspaper . 5th September 2019.

[7] G-BA : Dossier on the benefit assessment according to Section 35a SGB V - Ravulizumab (Ultomiris®) from July 25, 2019. Accessed June 4, 2020 . (PDF).