Biologics Drug Discovery and Development - Essay Example

 Introduction to Biologics Biologics is the new development of medicines using human or animal proteins that are engineered to support the body’s immune system and to assist in treating, curing and preventing diseases. Biologics can be found in vaccines, blood components and as living cells in therapeutic treatments. Biologics can be actual cells obtained from the body or other components such as sugars, nucleic acids or proteins. While whole blood, organ and tissue transplants and stem cell therapy are considered a form of biologics, the term is used more for those products which are created or engineered from DNA. Biologics is now finding a place in research studies as possible solutions for diseases that have not responded well to traditional drugs. Application to Biologics for the Treatment of Patients Biologics have now been used for a number of diseases such as Crohn’s Disease, rheumatoid arthritis (RA), and have highly impacted the fields of oncology, neurology, cardiology and gastroenterology. In RA, human genes are genetically engineered to inhibit particular areas of the body’s immune system that play a large part in inciting inflammation, a common feature of RA. This is used primarily when other drug treatments have failed and, when applied aggressively, it is shown to help prevent long-term disability. Some of the current biologic drugs on the market are: Actemra, Cimzia, Enbrel, Humira, Kineret, Xeljanz, and others. These biologics treat midrange to severe RA and target specific components of the immune system that cause inflammation, rather than just a number of areas. It can be used alone or in conjunction with other medications (WebMD 2013). Some reactions to taking biologics include rash and pain, usually at the site of injection, however, the rate is fairly low at 30%. As an intravenous injection, it can also bring on flu symptoms, fever, chills, headaches and nausea. As it suppresses the immune system, this can bring on a latent susceptibility to various illnesses, so it must be monitored very closely at the time of injection, and for a while afterwards. Each drug may produce different reactions. Actemra, as an example, may cause upper respiratory tract infections, high blood pressure and an elevated liver enzyme level. Cimza can also cause upper respiratory infections along with high blood pressure, but also back pain as well (WebMD 2013). These drugs are given in different ways as well: Actemra requires an hour-long infusion (IL-6) in a once-a-month application while Cimzia is a simple injection from a prefilled syringe and is taken every two to four weeks, depending on the dosage prescribed. There are certain times when biologics cannot be taken: when a person has multiple sclerosis, congestive heart failure, tuberculosis, or is currently receiving vaccines. Pregnant women should not take them unless it is desperately needed. Those who are having surgery should cease taking their biologic treatments until they have recovered and wounds have healed. Biologic Therapies Have Many Contrasting Features to Small Molecules As part of cancer therapy studies, targeting the estimated glomerular filtration rate (eGFR) of the body’s kidney filtration system, provides a huge contribution to understanding what actually works best in medical solutions. As a natural occurrence, monoclonal antibodies (mAbs) are proteins produced by the immune system in response to any foreign proteins, known as antigens. These mAbs bind to the antigens on the part called the epitope. In response, phagocytes move in to destroy the antigen (Kohzoh & Takaoka 2006). In earlier years, eGFR-targeted therapy led to the development of small-molecule eGFR tyrosine kinase inhibitors (TKIs). Newer biologics in the form of therapeutic mAbs comes with huge monetary costs and complex processes in development, yet many biotech and pharmaceutical companies are working more in this field than in the small molecules field. This is because the mAbs show more success in both chimeric (18%) and humanized mAbs (24%). The differences between the older applications and the newer ones are that the anti-eGFR mAbs are larger proteins and can be delivered intravenously while the eGFR TKIs are available synthetically and are delivered orally. Also, the mAb has a longer life span of 3 to 7 days, requiring only a weekly dosage whereas the small molecule TKIs must be delivered every 36 hours (Kohzoh & Takaoka 2006). Therapeutic mAbs show an advantage in binding to antigens at the tumour-cell delivery surface site but small-molecule agents are better when applied to haematological tumours. Modify Drug Discovery Pathway Accordingly In the above example of cancer treatments, and comparing mAbs and TKIs in regards to application delivery, one works better as an oral medication but must be taken more often. The other works better as an injection onto the tumour surface and only needs a once-a-week application. Determining how different drugs work best require a lot of years in research studies and many failures besides the huge costs involved with experimentations. While obvious failures will occur, notating the results and conditions of the test means that the test does not need to be repeated unless the variables involved change, then a different test is required. As shown in the previous situation, when determining that a biologic should be delivered to the surface of a cancer in the brain, for example, it takes quite a few years to come to that conclusion. If someone were severely allergic, however, to the injection, then an alternative method must be found, usually that of an oral application or else, an entirely different application altogether (Corr & Williams 2009). Dual NCE/NBE Approach NCE stands for new chemical entity and NBE stands for neuro-bioenergetics. Some medical practitioners will combine the use of an NCE and an NBE, such as acupuncture, which would help with pain management. One could say that in this arrangement, it is a matter of the East meets the West in terms of medical applications. This would be especially useful in the case of RA where there may be significant pain, depending on the stage of the disease. While the drug application takes care of the cellular repairs, acupuncture, as one form of NBE, would help alleviate pain on a quicker basis. Other applications in NBE are nutritional supplements, homeopathy, although that is dependent on the medicine being taken. Utilizing NBE is more concerned with combining the mind with the body rather than just treating the body itself and failing to help with emotional and mental adjustments. It is well understood that the mind has a direct effect on the body and how it copes with pain and illness. Therefore, treating the mind and emotions, as well as the biological body, is essential to returning to a state of wellness. Drug Discovery Key Issues Relating to Biologics Every day there is something new being discovered, and in biologics, the Crescendo Mouse is one of the latest discoveries. In research experiments, a transgenic mouse has generated fully human antibodies in vivo, through the natural process of B cell maturation and, without further manipulation, it creates very strong therapeutics, such as the VH single domain fragment. The expectation is that the mouse can enable ‘rapid generation of superior therapeutic products and fully realise the potential of human VH fragments’ for the future (Crescendo Mouse 2013). VH fragments are the smallest antibody fragments which can retain binding to specific targets and have significant advantages in ease of engineering and are robust. They have been validated in the clinic with several products, up to phase 2/proof of concept. These are most suited for a local or topical delivery system, have great stability and are the easiest to manufacture. Resources Corr, P & Williams, D 2009, ‘The Pathway from Idea to Regulatory Approval: Examples for Drug Development,’ National Academy of Sciences, NCBI, Available from < http://www.ncbi.nlm.nih.gov/books/NBK22930/> [16 May 2013] Drug Discovery Today 2013, Crescendo Biologics Announces the Crescendo Mouse, Drug Discovery Today Online, Available from < http://www.drugdiscoverytoday.com/view/30267/crescendo-biologics-announces-the-crescendo-mouse/> [16 May 2013] Kohzoh, I & Takaoka, A 2006, ‘Comparing Antibody and Small-Molecule Therapies for Cancer,’ Medscape Today News, Available from < http://www.medscape.com/viewarticle/550008_3> [17 May 2013] WebMD 2013, ‘Biologics for Rheumatoid Arthritis Treatment,’ WebMD Online, Available from < http://www.webmd.com/rheumatoid-arthritis/guide/biologics> [17 May 2013] Read More