      Document 0153
 DOCN  DRG0153
 UNIQUE IDENTIFIER        DRG-0094
 NAME OF SUBSTANCE        Sevirumab [USAN 1996]
 REGISTRY NUMBER          138660-96-5
 SYNONYMS                 HMA-CMV [FDA 071A]
 SYNONYMS                 SDZ MSL 109 [FDA 071A]
 SYNONYMS                 SDZ 89-109 [FDA 071A]
 SYNONYMS                 MSL-109 [AmFAR Tx Dir 1993;6(3)]
 SYNONYMS                 Protovir [NIAID ACTG 294]
 SYNONYMS                 Human monoclonal antibody to cytomegalovirus
                          [Int Conf AIDS 1992 Jul 19-24;8(2)]
 PROTOCOL ID NUMBERS      FDA 071A
 PROTOCOL ID NUMBERS      FDA 071B
 PROTOCOL ID NUMBERS      NIAID ACTG 266
 PROTOCOL ID NUMBERS      NIAID ACTG 294
 SECONDARY SOURCE ID      Study No. B102 [FDA 071A]
 SECONDARY SOURCE ID      Study No. B103 [FDA 071B]
 PHARMACOLOGICAL ACTION   MODE OF ACTION: In vitro, it has been shown
                          to bind to the surface membrane on
                          CMV-infected cells. It is an IgG1 with high
                          neutralizing activity against CMV strains and
                          no cross reactivity with other herpes
                          viruses. It is well tolerated with a T 1/2
                          approaching native immunoglobulin in HIV
                          seropositive recipients. An initial study of
                          MSL-109 in patients with AIDS showed that it
                          was well tolerated, the development of
                          antibody was not observed, and that at the
                          higher dose levels peak and trough serum
                          levels greatly exceed the in vitro
                          sensitivity of CMV to the antibody
                          preparation. [AmFAR Tx Dir 1993;6(3)] [Sixth
                          International Conference on AIDS, San
                          Francisco, 1990 Petersen et al., abstract no
                          Th.B.442]
 DISEASES STUDIED/TREATED Cytomegalovirus infection [AmFAR Tx Dir
                          1993;6(3)]
 CLASSIFICATION CODE      Antiviral [AmFAR Tx Dir 1993;6(3)]
 CLASSIFICATION CODE      Immunomodulator [FDA 071A]
 SUBSTANCE INTERACTIONS   Interacts with amphotericin B; fluconazole;
                          and biologicals including immunoglobulin
                          therapy, granulocyte macrophage-colony
                          stimulating factor (GM-CSF), erythropoietin
                          alpha, or any interleukin. [FDA 071A] [FDA
                          071B]
 ADVERSE EFFECTS          No adverse effects related to MSL-109 have
                          been noted in animals or bone-marrow
                          transplant patients. In a pharmacokinetics
                          and toxicity study, no laboratory
                          abnormalities, evidence for immune complex
                          formation or development of antiidiotypic
                          antibody were noted. [AmFAR Tx Dir 1993;6(3)]
                          [Sixth International Conference on AIDS, San
                          Francisco, 1990 Petersen et al., Abstract No
                          Th.B.442]
 CONTRAINDICATIONS        Contraindicated in patients with previous
                          history of or evidence of idiopathic
                          thrombocytopenia purpura, agammaglobulinemia,
                          or hypogammaglobulinemia; significant
                          pulmonary dysfunction; uncontrolled or
                          unstable diabetes; significant cardiovascular
                          disease including uncontrolled hypertension,
                          congestive heart failure, cardiac arrhythmia,
                          angina pectoris, or history of myocardial
                          infarction (within one year); coagulation or
                          hemorrhagic disorders; active severe
                          opportunistic infection; severe concomitant
                          clinical condition; or prior treatment with
                          monoclonal antibodies derived from any animal
                          species. Also contraindicated in pregnant or
                          breastfeeding women. [FDA 071B] [FDA 071A]
 CHEMICAL/PHYSICAL DATA   DRUG DESCRIPTION: An antiviral monoclonal
                          antibody produced in a stable hybridoma cell
                          line after in vitro stimulation with CMV
                          [AmFAR Tx Dir 1993;6(3)]
 CHEMICAL/PHYSICAL DATA   MOLECULAR WEIGHT: Approximately 150000
                          daltons [USAN 1996]
 SUBSTANCE DELIVERY DATA  MODE OF DELIVERY: Intravenous. [Sixth
                          International Conference on AIDS, San
                          Francisco, 1990 Petersen et al., abstract no
                          Th.B.442]
 MANUFACTURERS            Protein Design Labs
 REFERENCES               Tolpin M, Pollard R, Tierney M, Nokta M, Wood
                          D, Hirsch M. Combination therapy of
                          cytomegalovirus (CMV) retinitis with a human
                          monclonal anti-CMV antibody (SDZ MSL 109) and
                          either ganciclovir (DHPG) or foscarnet (PFA).
                          Int Conf AIDS. 1993 Jun 6-11;9(1):54
                          (abstract no. WS-B11-2).
 REFERENCES               Pollard R, Nokta MA, Pappas P, Holloway M,
                          Borucki MJ, Wood DL, Zitelli AM, Tolpin MD,
                          Nadler PI, Whitley RJ. An
                          anti-cytomegalovirus human monoclonal
                          antibody in individuals with AIDS: a phase
                          I/IIA study. Int Conf AIDS. 1992 Jul
                          19-24;8(2):B126 (abstract no. PoB 3237).
 REFERENCES               Emanuel DJ. Uses of immunotherapy for control
                          of human cytomegalovirus-associated diseases.
                          Transplant Proc. 1991 Jun;23(3 Suppl
                          3):144-6.
 REFERENCES               Drobyski WR, Gottlieb M, Carrigan D, Ostberg
                          L, Grebenau M, Schran H, Magid P, Ehrlich P,
                          Nadler PI, Ash RC. Phase I study of safety
                          and pharmacokinetics of a human
                          anticytomegalovirus monoclonal antibody in
                          allogeneic bone marrow transplant recipients.
                          Transplantation. 1991 Jun;51(6):1190-6.
 REFERENCES               Aulitzky WE, Schulz TF, Tilg H, Niederwieser
                          D, Larcher K, Ostberg L, Scriba M, Martindale
                          J, Stern AC, Grass P, et al. Human monoclonal
                          antibodies neutralizing cytomegalovirus (CMV)
                          for prophylaxis of CMV disease: report of a
                          phase I trial in bone marrow transplant
                          recipients. J Infect Dis. 1991
                          Jun;163(6):1344-7.
 REFERENCES               Petersen E, Kaplan C, Fish D, Hersh E,
                          Grayson J, Gray J, Masuho Y. Human monoclonal
                          antibody to cytomegalovirus (TI-23);
                          pharmacokinetics and toxicity study in HIV
                          seropositive patients. Int Conf AIDS. 1990
                          Jun 20-23;6(1):232 (abstract no. Th.B.442).
 REFERENCES               Skarp-Osberg I, Hokeberg I, Olding-Stenkvist
                          E, Tufveson G. Use of a human monoclonal
                          anti-cytomegalovirus antibody for the
                          treatment of severe cytomegalovirus after
                          renal transplantation. Transplant Proc. 1990
                          Feb;22(1):234.
 ENTRY MONTH              9011
 LAST REVISION DATE       951201
 

SOURCE: National Library of Medicine, Bethesda, MD.  Distributed by AEGIS.
