Avicine, tested and developed by

AVI BioPharma Sarepta Therapeutics, Inc. () is a medical research and drug development company with corporate offices and research facilities in Cambridge, Massachusetts, United States. Incorporated in 1980 as AntiVirals, , archiveurl = http://www.gene-tools. ...

, and also known as CTP-37 was trialled as a possible

cancer vaccine A cancer vaccine is a vaccine that either treats existing cancer or prevents development of cancer. Vaccines that treat existing cancer are known as ''therapeutic'' cancer vaccines or tumor antigen vaccines. Some of the vaccines are "autologous", ...

to treat a number of different

cancer Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal b ...

s. These included

colorectal cancer Colorectal cancer (CRC), also known as bowel cancer, colon cancer, or rectal cancer, is the development of cancer from the colon or rectum (parts of the large intestine). Signs and symptoms may include blood in the stool, a change in bowel m ...

pancreatic cancer Pancreatic cancer arises when cell (biology), cells in the pancreas, a glandular organ behind the stomach, begin to multiply out of control and form a Neoplasm, mass. These cancerous cells have the malignant, ability to invade other parts of t ...

and

prostate cancer Prostate cancer is cancer of the prostate. Prostate cancer is the second most common cancerous tumor worldwide and is the fifth leading cause of cancer-related mortality among men. The prostate is a gland in the male reproductive system that sur ...

. The treatment was trialled as and intended to be induced via

intramuscular injection Intramuscular injection, often abbreviated IM, is the injection of a substance into a muscle. In medicine, it is one of several methods for parenteral administration of medications. Intramuscular injection may be preferred because muscles have ...

into the bloodstream, the location dependent on the treatment area. Common

side effect In medicine, a side effect is an effect, whether therapeutic or adverse, that is secondary to the one intended; although the term is predominantly employed to describe adverse effects, it can also apply to beneficial, but unintended, consequence ...

s during

clinical trial Clinical trials are prospective biomedical or behavioral research studies on human participants designed to answer specific questions about biomedical or behavioral interventions, including new treatments (such as novel vaccines, drugs, dietar ...

s included

fever Fever, also referred to as pyrexia, is defined as having a body temperature, temperature above the human body temperature, normal range due to an increase in the body's temperature Human body temperature#Fever, set point. There is not a single ...

and

chills Chills is a feeling of coldness occurring during a high fever, but sometimes is also a common symptom which occurs alone in specific people. It occurs during fever due to the release of cytokines and prostaglandins as part of the inflammatory r ...

as experienced with many other conventional

vaccine A vaccine is a biological Dosage form, preparation that provides active acquired immunity to a particular infectious disease, infectious or cancer, malignant disease. The safety and effectiveness of vaccines has been widely studied and verifie ...

s. The vaccine operated by eliciting

antibodies An antibody (Ab), also known as an immunoglobulin (Ig), is a large, Y-shaped protein used by the immune system to identify and neutralize foreign objects such as pathogenic bacteria and viruses. The antibody recognizes a unique molecule of the ...

against

human chorionic gonadotropin Human chorionic gonadotropin (hCG) is a hormone for the maternal recognition of pregnancy produced by trophoblast cells that are surrounding a growing embryo (syncytiotrophoblast initially), which eventually forms the placenta after implantation ...

(hCG) a cancer associated

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...

expressed by most

cancer cell Cancer cells are cells that divide continually, forming solid tumors or flooding the blood with abnormal cells. Cell division is a normal process used by the body for growth and repair. A parent cell divides to form two daughter cells, and these d ...

s, with the goal of prolonged survival for those affected. Avicine was originated by AVI BioPharma in the

USA The United States of America (U.S.A. or USA), commonly known as the United States (U.S. or US) or America, is a country Continental United States, primarily located in North America. It consists of 50 U.S. state, states, a Washington, D.C., ...

, who licensed the product to SuperGen. However, due to delays in clinical testing, as a result of research difficulties, the owners of Avicine were forced to direct their attention to other areas being the investigation and treatment of cardiovascular and infectious disease indications.

Medical Uses

Avicine never reached the commercial treatment phase as research was discontinued on 15 January 2007. The cancers Avicine was designed to manage were,

pancreatic The pancreas is an Organ (anatomy), organ of the digestive system and endocrine system of vertebrates. In humans, it is located in the abdominal cavity, abdomen behind the stomach and functions as a gland. The pancreas is a mixed or heterocrine ...

colorectal The large intestine, also known as the large bowel, is the last part of the gastrointestinal tract and of the digestive system in tetrapods. Water is absorbed here and the remaining waste material is stored in the rectum as feces before being ...

and

. In a one-year, Phase II Avicine cancer vaccine study, a group of

patient A patient is any recipient of health care services that are performed by healthcare professionals. The patient is most often ill or injured and in need of treatment by a physician, nurse, optometrist, dentist, veterinarian, or other health c ...

s were treated with Avicine alongside the combination of

Gemcitabine Gemcitabine, with brand names including Gemzar, is a chemotherapy medication. It treats cancers including testicular cancer, breast cancer, ovarian cancer, non-small cell lung cancer, pancreatic cancer, and bladder cancer. It is administered by i ...

(Gemzar), the results yielding that Avicine could be induced alongside

Gemzar Gemcitabine, with brand names including Gemzar, is a chemotherapy medication. It treats cancers including testicular cancer, breast cancer, ovarian cancer, non-small cell lung cancer, pancreatic cancer, and bladder cancer. It is administered by ...

, in the

prostate The prostate is both an Male accessory gland, accessory gland of the male reproductive system and a muscle-driven mechanical switch between urination and ejaculation. It is found only in some mammals. It differs between species anatomically, ...

region. As the

3rd Third or 3rd may refer to: Numbers * 3rd, the ordinal form of the cardinal number 3 * , a fraction of one third * Second#Sexagesimal divisions of calendar time and day, 1⁄60 of a ''second'', or 1⁄3600 of a ''minute'' Places * 3rd Street (d ...

and 4th clinical trials were not done this was never done as a commercial treatment.

Contraindications and drug interactions

Patients who were

pregnant Pregnancy is the time during which one or more offspring develops (gestation, gestates) inside a woman, woman's uterus (womb). A multiple birth, multiple pregnancy involves more than one offspring, such as with twins. Pregnancy usually occur ...

were not to be treated by Avicine, as it elicits

against hCG, a cancer associated oncofoetal protein that is also prevalent during the development of a child in the

womb The uterus (from Latin ''uterus'', plural ''uteri'') or womb () is the organ in the reproductive system of most female mammals, including humans that accommodates the embryonic and fetal development of one or more embryos until birth. The uter ...

. As of 2007, due to the discontinued state of Avicine research, drug interactions have not been studied.

Adverse Effects

Results from a multi-center phase II study in test subjects with

metastatic colorectal cancer Colorectal cancer (CRC), also known as bowel cancer, colon cancer, or rectal cancer, is the development of cancer from the colon or rectum (parts of the large intestine). Signs and symptoms may include blood in the stool, a change in bowel mo ...

in USA exposed that of 64 patients some experienced

s and

. Overall, the

s were tolerated well by the patients. 69% (55 of the 73 patients).

Key Development Milestones

Colorectal Cancer

After successfully completing a Phases I and II trials for the use of Avicine in

, a phase III licensing trail began to investigate Avicine as a first line treatment for

patients alongside

chemotherapy Chemotherapy (often abbreviated to chemo and sometimes CTX or CTx) is a type of cancer treatment that uses one or more anti-cancer drugs (chemotherapeutic agents or alkylating agents) as part of a standardized chemotherapy regimen. Chemotherap ...

in January 2001. The trial was randomised where the patients would either receive Avicine in combination with chemotherapy or chemotherapy unaided. However, Phase III was discontinued as of 15 January 2007.

Pancreatic Cancer

A multi-centre Phase II clinical trial of Avicine was conducted by

Avi Biopharma Sarepta Therapeutics, Inc. () is a medical research and drug development company with corporate offices and research facilities in Cambridge, Massachusetts, United States. Incorporated in 1980 as AntiVirals, , archiveurl = http://www.gene-tools. ...

, including 55 patients in the US. The trial was conducted 10 patients with

saw positive results in a pilot phase II trial of Avicine. A plan was proposed to begin a phase III trial for patients with pancreatic cancer. However, in 2003 it was reported in order to do so an additional corporate partner was needed for the trial to be instigated. Research was discontinued on 15 January 2007 as an additional corporate partner was found and phase II was still not complete.

Prostate Cancer

A phase I trial of Avicine was completed by Avi Biopharma in patients with

, however after this stage research was discontinued on 15 January 2007.

Drug Properties and Chemical Synopsis

Route of administration A route of administration in pharmacology and toxicology is the way by which a medication, drug, fluid, poison, or other substance is taken into the body. Routes of administration are generally classified by the location at which the substance i ...

: IM

Formulation Formulation is a term used in various senses in various applications, both the material and the abstract or formal. Its fundamental meaning is the putting together of components in appropriate relationships or structures, according to a formul ...

: unspecified

Class Class or The Class may refer to: Common uses not otherwise categorized * Class (biology), a taxonomic rank * Class (knowledge representation), a collection of individuals or objects * Class (philosophy), an analytical concept used differentl ...

Cancer Vaccines A cancer vaccine is a vaccine that either treats existing cancer or prevents development of cancer. Vaccines that treat existing cancer are known as ''therapeutic'' cancer vaccines or tumor antigen vaccines. Some of the vaccines are "autologous", ...

Mechanism of Action In pharmacology, the term mechanism of action (MOA) refers to the specific biochemical interaction through which a drug substance produces its pharmacological effect. A mechanism of action usually includes mention of the specific molecular targe ...

Immunomodulator Immunotherapy or biological therapy is the treatment of disease by activating or suppressing the immune system. Immunotherapies designed to elicit or amplify an immune response are classified as ''activation immunotherapies,'' while immunotherap ...

;

Immunostimulant Immunostimulants, also known as immunostimulators, are substances (drugs and nutrients) that stimulate the immune system by inducing activation or increasing activity of any of its components. One notable example is the granulocyte macrophage colon ...

WHO ATC code: L03A-X (Other immunostimulants) EPhMRA code: L3A (Immunostimulating Agents Excluding Intereferons)

Chemistry of Avicine

The

chemical A chemical substance is a form of matter having constant chemical composition and characteristic properties. Some references add that chemical substance cannot be separated into its constituent elements by physical separation methods, i.e., wi ...

and

physical properties A physical property is any property that is measurable, whose value describes a state of a physical system. The changes in the physical properties of a system can be used to describe its changes between momentary states. Physical properties are o ...

of Avicine can be highlighted in the table below:

Pharmacology

Avicine (CTP-37) is a peptide fragment of Human chorionic gonadotropin (hCG), an oncofoetal protein expressed by most cancer lines, the significant role of hCG being to ward off the

immune system The immune system is a network of biological processes that protects an organism from diseases. It detects and responds to a wide variety of pathogens, from viruses to parasitic worms, as well as cancer cells and objects such as wood splinte ...

, the same way cells of the developing

foetus A fetus or foetus (; plural fetuses, feti, foetuses, or foeti) is the unborn offspring that develops from an animal embryo. Following embryonic development the fetal stage of development takes place. In human prenatal development, fetal develo ...

ward off the immune system. In some studies expressions of hCG in colorectal cancer has been positively correlated with reduced survival rates. Two

epitope An epitope, also known as antigenic determinant, is the part of an antigen that is recognized by the immune system, specifically by antibodies, B cells, or T cells. The epitope is the specific piece of the antigen to which an antibody binds. The p ...

s can be found in CTP-37 one of which is dominant and can elicit anti-bodies against hCG. By employing this ideology Avi Biopharma created a modulated form of CTP-37 (Avicine) containing an extra peptide domain, more specifically denoted as a loop peptide. The modulation of the earlier formulation was done to force the immune system to act against multiple epitopes, with the aim of improving the survival rate of individuals with cancer. The moderated formula of Avicine was built on the basis of a study that indicated patients exhibited prolonged survival when they responded to more than one vaccine epitope. The majority of the world's population have been vaccinated against diphtheria use

diphtheria toxoid Diphtheria vaccine is a toxoid vaccine against diphtheria, an illness caused by ''Corynebacterium diphtheriae''. Its use has resulted in a more than 90% decrease in number of cases globally between 1980 and 2000. The first dose is recommended a ...

(DT), and was therefore used a

carrier protein A membrane transport protein (or simply transporter) is a membrane protein involved in the movement of ions, small molecules, and macromolecules, such as another protein, across a biological membrane. Transport proteins are integral transmembrane ...

due to the significant data available on its effects as a vaccine. Also, the established

immune response An immune response is a reaction which occurs within an organism for the purpose of defending against foreign invaders. These invaders include a wide variety of different microorganisms including viruses, bacteria, parasites, and fungi which could ...

to DT was also believed to be important in encouraging an immune response to hCG peptides.

Therapeutic Trials

Colorectal Cancer

Phase I tests demonstrated a satisfactory safety profile of Avicine (CTP37-diphtheria toxoid/DT), whilst also establishing the immunological activity of the drug. In the following Phase II study 77 patients with colorectal cancer were treated with Avicine using Active Specialised Immunization (ASI), the CTP37-DT, prompting

in patients experiencing cancers that expressed very high hCG levels. The patients were given the vaccine at week 0, 4, 10 and 16. Of the 77 patients 56 of those produced antibodies to human chorionic gonadotrophin (hCG), in response to the vaccine. By

intention-to-treat analysis In medicine an intention-to-treat (ITT) analysis of the results of a randomized controlled trial is based on the initial treatment assignment and not on the treatment eventually received. ITT analysis is intended to avoid various misleading artifac ...

it was observed that of the vaccinated patients the

median In statistics and probability theory, the median is the value separating the higher half from the lower half of a data sample, a population, or a probability distribution. For a data set, it may be thought of as "the middle" value. The basic fe ...

survival was 34 weeks. The median survival of patients who those who did not produce antibodies from the vaccine was 17 weeks, whilst the patients who developed antibodies from the vaccine exhibited a median survival of 42 weeks. Also, patients who developed median antibody levels (n=39) expressed higher survival rates than those who expressed antibody levels below the median value (n=38), where survival rates were 45 weeks and 24 weeks respectively (AVI BioPharma Inc.). Additionally, CTP-37 consists of two

s and those who responded to both epitopes demonstrated prolonged survival, with 65 weeks, compared to those who only reacted against one epitope who experienced a 39-week survival rate. Another randomised group was also given Pharmacia-Upjohn's Camptosar, where the subjects experienced a mean 35 weeks survival rate. Using this data AVI Biopharma formulated a new version of CTP-37 vaccine, which included another hCG peptide referred to as the loop peptide. Inclusion of the loop peptide is used primarily to modulate the dominance of the original substance, which would ideally force the immune system to react to the multiple epitopes, culminating with prolonged survival rates for colorectal cancer patients.

Pancreatic Cancer

patients were included in a study which confirmed treatment with Avicine produces comparable survival rates to treatment with

. A group was also tested with gemcitabine combined with Avicine, and expressed significantly better survival rates than those who were treated with either substance independently. Also, Gemcitabine did not affect the patients ability to have an immune response to Avicine's epitopes. Data from a phase Ib study including ten patients with pancreatic cancer established the safety and value of the use of Avicine in the subjects. The patients survived for periods greater than 6 months, which were historical survival rates for patients with metastatic pancreatic cancer. During the phase II study, one patient survived greater than 20 months, three lived more than 11 months, and 4 out of 6 patients remaining exceeded the 5.3 month period of median historical survival for this disease in 2001. The median survival in the 10 pancreatic patients was equal to 33 weeks with the Avicine (CTP-37) vaccine.

References

{{DEFAULTSORT:Avicine Vaccines Cancer vaccines Peptide vaccines