(Consensus Interferon)
Infergen (Consensus Interferon) is a bio-optimized, selective and highly potent type 1 interferon alpha
launched in
the United States in 1997. It is currently indicated as monotherapy for the treatment of adult patients suffering from
chronic hepatitis C viral infections with compensated liver disease and is dosed three times per week.
Infergen is
the only interferon with data in the label regarding use in patients following relapse or non-response to non-pegylated
interferons.
Infergen, or Interferon alfacon-1, is a recombinant non-naturally occurring type-I interferon. The 166
amino acid
sequence of interferon alfacon-1 was derived by scanning the sequences of several natural interferon alpha subtypes and
assigning the most frequently observed amino acid in each corresponding position. Four additional amino acid changes
were made to facilitate the molecular construction, and a corresponding synthetic DNA sequence was constructed using
chemical synthesis methodology. Interferon alfacon-1 differs from interferon alfa-2b at 20/166 amino acids (88%
homology), and comparison with interferon-beta shows identity at over 30% of the amino acid positions. Interferon
alfacon-1 is produced in Escherichia coli (E. coli) cells that have been genetically altered by insertion of a
synthetically constructed sequence that codes for interferon alfacon-1. Prior to final purification, interferon
alfacon-1 is allowed to oxidize to its native state, and its final purity is achieved by sequential passage over a
series of chromatography columns. This protein has a molecular weight of 19,434 daltons and is also referred to as
consensus interferon (CIFN).
Interferons are a family of naturally occurring, small protein molecules with molecular weights of 15,000 to 21,000
daltons that are produced and secreted by cells in response to viral infections or to various synthetic and biological
inducers. Two major classes of interferons have been identified, type-I and type-II. Type-I interferons include a family
of more than 25 alpha interferons, as well as beta interferon and omega interferon. While all alpha interferons have
similar biological effects, not all the activities are shared by each alpha interferon and, in many cases, the extent of
activity varies substantially for each interferon subtype.
Valeant Pharmaceuticals is conducting a randomized, open-label, Phase 3 investigational research study, Daily-Dose Consensus Interferon and Ribavirin: Efficacy of Combined Therapy (DIRECT). DIRECT will evaluate the safety and efficacy of daily administration of subcutaneous interferon alfacon-1 plus ribavirin versus no treatment in HCV patients who have not responded to previous combination therapy with peglyated interferon alfa plus ribavirin. (Read more about the 24 week results of the DIRECT trial).
In addition, a multicenter, randomized open label, parallel group trial has been initiated. A Study of daily Consensus Interferon and Ribavirin in HCV Patients that Achieved a Partial Response to Peglyated Interferon and Ribavirin (ENHANCE) is underway. ENHANCE is aimed at evaluating the efficacy and safety of daily Consensus interferon and ribavirin in patients who were partial responders to combination therapy with peglyated interferon and ribavirin at week 12.
Valeant posts protocol information for all ongoing Phase 2, 3, and 4 trials to the National Institutes of Health’s (NIH) ClinicalTrials.gov website. To learn more about the clinical trials that are under way or to find out if a study is enrolling patients in your area, please visit www.clinicaltrials.gov.
According to the Centers for Disease Control and Prevention, an estimated 3.9 million Americans (1.8 percent) have been
infected with the hepatitis C virus (HCV). HCV causes an estimated 10,000 to 12,000 deaths annually in the United States
and is the leading cause of the need for liver transplants. The prevalence of HCV is increasing and approximately half
of all patients with chronic HCV disease do not respond to first-line treatment. The treated non-responder patient
population is expected to grow from 15,000 patients in 2003 to 161,000 patients in 2013.
HCV resides in blood and is spread when infected blood from one person enters the body of another. Common causes of
infection are intravenous drug use, accidental needle sticks in the healthcare environment, and children born to HCV
positive mothers. It is also possible to spread HCV sexually. HCV is not spread through casual contact.
Hepatitis C testing is recommended for those who*:
- Ever injected illegal drugs.
- Received clotting factors made before 1987.
- Received blood or organs before July 1992.
- Ever were treated with hemodialysis.
- Have undiagnosed liver disease.
- May have a needlestick/sharp or mucosal exposure to HCV-positive blood.
- Are 12 to 18 months of age, and are born to HCV-positive women.
* Hepatitis Foundation International, Hepatitis C, Rev. 02.2006
Alpha interferons, including Interferon alfacon-1, cause or aggravate fatal or life-threatening
neuropsychiatric, autoimmune, ischemic, and infectious disorders.
Patients should be monitored closely with periodic clinical and laboratory evaluations. Patients with
persistently severe or worsening symptoms of these conditions should be withdrawn from therapy. In many but
not all cases, these disorders resolve after stopping Interferon alfacon-1 therapy.
See CONTRAINDICATIONS, WARNINGS, PRECAUTIONS and ADVERSE REACTIONS.
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INFERGEN is contraindicated in patients with known hypersensitivity to alpha interferons or to any
component of the
product, in patients with decompensated hepatic disease and autoimmune hepatitis. Development of or exacerbation of
autoimmune disorders (e.g. autoimmune thrombocytopenia, idiopathic thrombocytopenic purpura, psoriasis, rheumatoid
arthritis) have been reported in patients receiving alpha interferon therapies, including INFERGEN.
Treatment with INFERGEN should be administered under the guidance of a qualified physician, and may lead to
moderate-to-severe adverse experiences requiring dose reduction, temporary dose cessation, or discontinuation of further
therapy.
Severe psychiatric adverse events may manifest in patients receiving therapy with alpha interferons, including INFERGEN.
Depression, suicidal ideation, suicide attempt, and suicide may occur. Other prominent psychiatric adverse events may
also occur, including psychosis, aggressive behavior, nervousness, anxiety, emotional lability, abnormal thinking,
agitation, apathy and relapse of drug addiction. INFERGEN should be used with extreme caution in patients who report a
history of depression. Physicians should monitor all patients for evidence of depression and other psychiatric symptoms.
In severe cases, therapy should be stopped immediately and psychiatric intervention instituted.
Bone Marrow Toxicity: Alpha interferons suppress bone marrow function and may result in severe cytopenias including very
rare events of aplastic anemia. It is advised that complete blood counts be obtained pretreatment and monitored
routinely during therapy. Alpha interferon therapy should be discontinued in patients who develop severe decreases in
neutrophil (0.5 x 109/L) or platelet counts (<50 x 109/L).
Hypertension, tachycardia, palpitation, and tachyarrythmias have been reported in patients treated with INFERGEN.
INFERGEN should be administered with caution to patients with preexisting cardiac disease. Supraventricular arrhythmias,
chest pain, and myocardial infarction have been associated with alpha interferon therapies.
Pneumonia and interstitial pneumonitis, some resulting in respiratory failure and/or patient deaths, have been induced
or aggravated by alpha interferon therapy, including INFERGEN. Patients who develop persistent or unexplained pulmonary
infiltrates or pulmonary function impairment should discontinue treatment with INFERGEN.
Chronic hepatitis C patients with cirrhosis may be at risk of hepatic decompensation when treated with alpha
interferons, including INFERGEN. During treatment, patients' clinical status and hepatic function should be closely
monitored, and INFERGEN treatment should be immediately discontinued if symptoms of hepatic decompensation, such as
jaundice, ascites, coagulopathy, or decreased serum albumin, are observed.
Ophthalmologic Disorders: Decrease or loss of vision, retinopathy including macular edema, retinal artery or vein
thrombosis, retinal hemorrhages and cotton wool spots; optic neuritis, and papilledema are induced or aggravated by
treatment with INFERGEN or other alpha interferons. All patients should receive an eye examination at baseline. Patients
with preexisting ophthalmologic disorders (e.g., diabetic or hypertensive retinopathy) should receive periodic
ophthalmologic exams during interferon alpha treatment. INFERGEN therapy should be discontinued in patients who develop
new or worsening ophthalmologic disorders.
Ischemic and hemorrhagic cerebrovascular events including hemorrhagic stroke have been observed in patients being
treated with INFERGEN. In addition, transient ischemic attack has been reported in young patients being treated with
INFERGEN without other reported risk factors.
INFERGEN should be discontinued immediately and appropriate medical treatment instituted if hypersensitivity reactions
occur. INFERGEN should be administered with caution to patients with a history of endocrine disorders and should be
discontinued immediately in patients who develop signs and symptoms of colitis. In addition, INFERGEN should be
suspended in patients with signs and symptoms suggestive of pancreatitis and discontinued in patients diagnosed with
pancreatitis.
The most common adverse events reported for INFERGEN during clinical studies were headache (82%), fatigue (69%), fever
(61%), myalgia (58%), rigors (57%), body pain (54%), arthralgia (51%), nausea (40%), insomnia (39%), pharyngitis (34%),
nervousness (31%), infection upper respiratory (31%), diarrhea (29%), depression (26%), anorexia (24%), injection site
erythema (23%), granulocytopenia (23%), dizziness (22%), cough (22%), dyspepsia (21%), thrombocytopenia (19%), anxiety
(19%), sinusitis (17%), influenza-like symptoms (15%) and leucopenia (15%).
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