Gusperimus

Gusperimus

Clinical data
Routes of administration	Intravenous infusion in normal saline or subcutaneous injection
ATC code	L04AA19 (WHO)
Legal status
Legal status	Rx-only (available only as orphan drug and for clinical studies)
Pharmacokinetic data
Bioavailability	100% (i.v. application)
Identifiers
IUPAC name 1-Amino-19-guanidino-11-hydroxy-4,9,12-triazanonadecane-10,13-dione
CAS Number	84937-45-1
PubChem CID	91271
E number	{{#property:P628}}
ECHA InfoCard	{{#property:P2566}}
Chemical and physical data
Formula	C17H40Cl3N7O3
Molar mass	496.903 g/mol

Gusperimus is an immunosuppressive drug. It is a derivative of the antitumor antibiotic spergualin, and inhibits the interleukin-2-stimulated maturation of T cells to the S and G2/M phases and the polarization of the T cells into IFN-gamma-secreting Th1 effector T cells, resulting in the inhibition of growth of activated naive CD4 T cells.

Gusperimus was developed by Bristol-Myers Squibb. Currently, it is manufactured and sponsored for use as an orphan drug and for clinical studies by the Japanese company Euro Nippon Kayaku. The patent claim (see quotation) is that gusperimus may be useful for a variety of hyperreactive inflammatory diseases such as autoimmune diseases. The drug is available in vials containing 100 mg each.

There is little information about the pharmacokinetic properties of gusperimus.

Indications

Approved

The European Commission assigned orphan drug status to gusperimus in 2001 for the treatment of Wegener's granulomatosis, a serious form of vasculitis frequently associated with permanent disability and/or fatal outcome. There have been cases of most ill patients resistant to all forms of usual treatment responding very well to gusperimus.

Investigational

It has been proposed that gusperimus may benefit patients with the neurological disease amyotrophic lateral sclerosis (ALS or Lou Gehrig's disease). ALS causes permanent motor deficits and disabilities up to the point that almost all motor functions, including breathing and bladder control, are lost. Patients usually have no intellectual impairments. Currently, there are no results from controlled studies in ALS patients.

There have also been positive and negative anecdotal reports in patients with multiple sclerosis. As with ALS, there are no sufficient studies in MS patients.

Gusperimus may possibly be of use in more common diseases and conditions such as rheumatoid arthritis, Crohn's disease, lupus erythematosus, and the prevention and therapy of transplant rejection or graft-versus-host disease.

Adverse effects

Currently, only provisional and preliminary data about side-effects is available. The following side-effects have been noticed so far:

• Dysgeusia (=abnormal or bad taste)
• Drug induced leukopenia (very common)
• Significant infections related to therapy.

It is not known if therapy with gusperimus may increase the risk of malignant diseases (lymphoma, leukemia, solid tumors), as is the case with other highly potent immunosuppressant agents such as ciclosporin or tacrolimus.

Interactions

There has been little experience about clinically relevant interactions. These might be:

• Other immunosuppressant drugs : Risk of infections increased.
• Myelotoxic drugs like 6-Mercaptopurin : Risk of serious bone marrow damage increased.
• Certain NSAIDs : Increased risk of hepatotoxic reactions.

Dosage

Gusperimus is used in therapeutic cycles. The daily dose and the length of each cycle as well as the length of the treatment free interval depend on the degree of leukopenia/neutropenia caused by gusperimus. It is recommended to obtain complete WBC (White Blood Cell) counts during and after each cycle frequently.

Synonyms

Common references are:

• (+−)-15-Deoxyspergualin,
• 1-Amino-19-guanidino-11-hydroxy-4,9,12-triazanonadecane-10,13-dione,
• 15-Deoxyspergualin,
• 15-Deoxyspergualin Hydrochloride,
• 7-{(Aminoiminomethyl)amino]-N-[2-[[4-[(3-aminopropyl)amino]butyl]amino]-
  1-hydroxy-2-oxoethyl]heptanamide,
• Gusperimus (Trihydrochloride),
• N-[[[4-[(3-Aminopropyl)amino]-butyl]carbamoyl]hydroxymethyl]-
  7-guanidinoheptanamide,
• Spanidin