Pharmaceutical

IFN Indications

Viruses | Influenza

Influenza (the flu) is a contagious respiratory illness caused by influenza viruses. It can cause mild to severe illness, and at times can lead to death. Influenza usually starts suddenly and may include the following symptoms: 1) fever (usually high), 2) headache, 3) tiredness (can be extreme), 4) cough, 5) sore throat, 6) runny or stuffy nose, 7) body aches, and 8) digestive problems such as diarrhea, nausea and vomiting. Complications of the flu can include bacterial pneumonia, ear infections, sinus infections, dehydration, and worsening of chronic medical conditions, such as congestive heart failure, asthma, or diabetes. Flu viruses spread mainly from person to person through coughing or sneezing. Sometimes people may become infected by touching something with flu viruses on it and then touching their mouth or nose. Most healthy adults may be able to infect others beginning 1 day before symptoms develop and up to 5 days after becoming sick. That means that a person may be able to pass on the flu to someone else before they know they are sick, as well as while they are sick.

Because interferon is naturally produced in the body, low dose IFN-αhas the potential to be a safe and effective prophylactic against the flu, as well as to lessen the severity and shorten the duration of infection.


Viruses | Hepatitis C

Hepatitis C is an infectious disease affecting the liver, caused by the hepatitis C virus (HCV). The infection is often asymptomatic, but once established, chronic infection can progress to scarring of the liver (fibrosis), and advanced scarring (cirrhosis) which is generally apparent after many years. In some cases, those with cirrhosis will go on to develop liver failure or other complications, including liver cancer. Those who develop cirrhosis or liver cancer may require a liver transplant, but the virus universally recurs after transplantation. An estimated 270-300 million people worldwide are infected with hepatitis C. No vaccine against hepatitis C is currently available.

The hepatitis C virus (HCV) is spread by blood-to-blood contact. Most people have few, if any, symptoms after the initial infection, yet the virus persists in the liver (chronic infection) in about 85% of those infected. The standard therapy for chronic HCV infection has historically been a combination of high-dose injectable interferon-alpha and oral ribavirin. The effectiveness of this treatment regimen is related to viral load and viral genotype. Up to half of patients with certain genotypes who initially respond to standard treatment by clearing the virus (complete virologic response), will relapse as evidenced by a re-emergence of HCV in their blood. In recent years, new direct-acting anti-viral drugs, such as boveprevir or telaprevir, have enhanced the combination of interferon and ribavirin, bringing the sustained virologic response rates to as high as 90%! This triple therapy of interferon + ribavirin + direct-acting anti-viral drug has become the new norm in treating hepatitis C. ABI’s lozenges could be ideal in combination with ribavirin and the direct-acting anti-virals making all three of the triple therapy drugs in hepatitis C treatment oral dosage forms, greatly improving the cost, convenience, and compliance of treatment. Additionally, the triple therapy that still includes high dose injectable interferon is not without side effects, and thrombocytopenia is one of the severe adverse effects that has been noted. Low-dose oral IFN-α has been shown to reverse thrombocytopenia, making it the ideal version of interferon to use in hepatitis C treatment. Furthermore, resistance has been of some concern with the new direct-acting antiviral drugs and relapse is always an issue with hepatitis C. Low-dose oral IFN-α has the potential to be used prophylactically to reduce relapse. In summary, ABI’s lozenges could make hepatitis C treatment more convenient and longer lasting with fewer of the harmful side effects.


Cancer

Immunotherapy is emerging as a new pillar in cancer treatment with greater potential to cure; however, many patients still fail to respond. The immunosuppressive tumor microenvironment is the pathological feature that underlies cancer therapy failure and allows tumors to continue to grow, undetected by the immune system. Exciting new research has shown that IFN-α has the ability to reprogram the leukemia microenvironment in a mouse model which enhances the anti-tumor activity of engineered T cell therapy. Furthermore, many cancers have mutations in toll-like receptors, which inhibit natural interferon production, and IFN-α treatment, as with ABI’s lozenge, could by-pass these blockades of normal immune function. Hematopoietic stem cell transplantation is the only hope for cure for patients with leukemia whose cancer has not responded to chemotherapy. In order to enhance the efficacy of stem cell transplants, efforts have been made to activate plasmacytoid dendritic cells (pDCs), the biggest producer of interferon-α, with synthetic oligonucleotides that bind to toll-like receptors on pDCs stimulating them to secrete interferon. While these experiments have been successful in-vitro, it has been observed that pDCs in humans are unable to produce interferon for up to 9 months post transplantation from either bone marrow or cord blood. An oral IFN-α lozenge could potentially bypass the need for functional pDCs and provide the immunostimulatory effect needed to enhance the efficacy of stem cell transplants.

Traditional chemotherapy regimens have many adverse effects and one of the more dangerous ones is thrombocytopenia in which platelets, the cells necessary for blood clotting, fall to dangerously low levels. Patients with unresolved thrombocytopenia are at risk for hemorrhaging. Low-dose oral IFN-α has been shown to prevent or reverse thrombocytopenia and ABI has the patent for treating thrombocytopenia with oral interferon. Given the ability of IFN-α to activate the immune system in the tumor microenvironment improving cancer immunotherapy, stimulate the immune system improving outcomes with hematopoietic stem cell transplantation, and prevent or reverse thrombocytopenia, a dangerous potential side-effect of chemotherapy, low-dose oral IFN-α in the form of ABI’s lozenges could be an ideal adjuvant therapy in most, if not all cancers!

There are certain cancers however, in which IFN-α might be of particular benefit. It is estimated that 15-25% of cancers are due to infection with an oncogenic virus. There are at present seven viruses known to exist that can cause cancer in humans: hepatitis B virus (HBV), hepatitis C virus (HCV), human Papillomavirus (HPV), gammaherpesviruses, namely Epstein-Barr virus (EBV), Kaposi’s Sarcoma-associated Herpesvirus (KSHV), Merkel Cell Polyomavirus (MCV), and Human T-cell lymphotrophic virus-1 (HTLV-1). These oncogenic viruses secrete viral interferon regulatory factors (vIRFs) that block endogenous production of interferons, allowing the viruses to escape detection by the immune system, sometimes remaining dormant for years. High-dose IFN-α has been used in the treatment of many of these cancers and in-vitro studies have shown that IFN-α suppresses HTLV-1 gene expression, while IFN-α combined with zidovudin induces apoptosis in HTLV-1-infected cells. High-dose injected IFN-α causes numerous adverse effects, whereas ABI’s lozenge delivers IFN-α to the mucus membranes at such a low dose that side effects are virtually eliminated.

Other Diseases of Interest


Myeloproliferative disorders

Influenza (the Polycethemia Vera (PV) is a myeloproliferative disorder in which a gain of function mutation in the Jak2 gene causes spontaneous erythropoiesis, resulting in an abnormally high hemoglobin, hematocrit, and red blood cell volume, putting patients at risk for thrombosis. Interestingly, although physiologic levels of interferon-α can stimulate hematopoiesis under certain conditions (like during an inflammatory response or in the case of thrombocytopenia), IFN-α is also able to bring abnormally elevated platelet levels back into the normal range, functioning as more of a hematopoietic regulator. This makes sense in terms of interferon’s dual anti-viral (sometimes needing to increase blood flow to an acute injury) and anti-proliferative (keeping a tight control on abnormal cell growth) activities.


Warts, cold sores, and canker sores

Warts are caused by HPV and cold sores are caused by HSV, both viruses that Interferon-α has been used to treat. Canker sores, also known as apthous stomatitis, are painful ulcerative sores in the mouth of unknown origin. While not life threatening, warts, cold sores, and canker sores are unpleasant and decrease quality of life. Individual warts can be removed, but if the underlying HPV virus is not treated, the warts will continue coming back. Cold sores and canker sores are especially vulnerable to ABI’s lozenges that dissolve in the oral mucosa in that they are on the receiving end of both the local and systemic immunostimulatory effects of the IFN-α at the same time.

Go to top