Biotherapeutics, as the drugs of the future, is attracting widespread attention nowadays. But the question is whether the small molecule approach is really on the way out? A biotherapeutics approach (it can be recombinant proteins, antibodies, engineered antibodies or newer developments such as RNA interference) allows one to address targets or biology that in some cases may not be as amenable to small molecule approaches. Also, small molecule drugs will always have a strong place in addressing diseases.
Although small molecule drugs remain the standard treatment for diseases, new strategies based on the engineering of proteins, genes and cells as therapeutic agents are there to revolutionise medicine in the near future. The areas may include gene therapeutics, tissue engineering, stem cell biology, cell-based therapeutics and gene correction technologies.
These biotherapeutic drugs target nearly 150 diseases and promise to bring better treatments to patients. However, if new biotherapeutics are to be made more accessible and affordable, most industry participants agree that improvements in performance and optimisation of processes are necessary. As the demand for production of biotherapeutics continues to grow, the question of whether current manufacturing capacity and production performance are sufficient to deal with the challenge becomes an important strategic issue.
For the global pharmaceutical and biotechnology industries the primary value driver of the genomic era will be an explosion of targets. Today's 400 or so targets are estimated to increase to at least 4,000 during the next decade. The $300 billion pharmaceutical market could grow to $3 trillion by 2020. These targets will be used both as diagnostic and focal points for developing new precision drugs.
Nano-biotherapeutics
CylImmune Sciences, Inc., a clinical stage nano-biotechnology company focused on the development and targeted delivery of multifunctional anti-cancer therapeutics. Aurimune is the company's lead compound. AuriTol is CylImmune's second patented clinical drug candidate. Both candidates are applications of CylImmune's patented pegylated colloidal gold tumor-targeting platform which is at the core of the company's drug pipeline. By coupling known cancer therapeutics to colloidal gold nanoparticles CylImmune intends to improve their biodelivery and efficacy. This approach should result in safer, more targeted and effective anti-cancer drugs.
Aurimune, has been shown to safety deliver Tumor Necrosis Factor (TNF) to tumors in pre-clinical studies. TNF, a known tumor-killing agent, is so toxic to healthy cells that it is not presently used as a systemic cancer treatment. By coupling TNF to CylImmune's nanoparticle, the compound avoids healthy organs and immune detection, while delivering a highly potent anti-cancer therapy directly to the tumor.
With an aim to boost its pipeline of biotech products, Pfizer Inc signed an agreement with CovX to acquire the privately-held biotherapeutics company. CovX's biotherapeutic platform is a technology that links therapeutic peptides to an antibody "scaffold". The peptide targets the disease while the antibody scaffold allows the peptide to remain in the body long enough to achieve therapeutic benefit. The technology thereby allows half-life extension and bioavailability to support optimal dosing regimens for peptide therapeutics.
Is the drug orphan?
The European Commission followed an opinion of the Committee for Orphan Medicinal Products (COMP) and has granted orphan drug designation to Talecris' alpha-1 proteinase inhibitor (human) for inhalation use in the treatment of congenital Alpha1-Antitrypsin Deficiency (AAT Deficiency or Alpha-1). Just now, there are no approved aerosolized treatments available for augmentation therapy for AAT Deficiency.
BIOSIMILARS Vs. BIOTHERAPEUTICS
Biosimilars are proteins, which are similar but not identical to the proteins used to treat chronic diseases. One drawback is that biosimilars may improve the accessibility of biotherapeutic treatments to those in developing nations. However, issues regarding the quality and effectiveness of treatments remain, along with concerns about the legal implications.
Biotherapeutics are proteins that are used as an active ingredient in some therapies to treat chronic diseases such as diabetes. In contrast, biosimilars are proteins which are similar to but not identical to therapeutic proteins. Biosimilars could make biotherapeutics more accessible to people in developing nations, as biotherapeutics are often expensive. Issues of effectiveness and quality arise as biosimilars are not identical to the original innovator product.
Proteins are complex molecules and as methods used to manufacture biotherapeutic proteins are not disclosed, variations in the manufacturing process are likely to occur. These, in turn, could cause slight variations in the biosimilar's structure, making it similar but not identical to the original therapeutic protein. Variations in a protein's structure will strongly influence its stability and bioactivity. This could influence in vivo activity and half-life by altering the rate of degradation. Consequently variations in both shelf-life and the severity of the immune reaction will occur.
Manufacturing methods may be altered at several different stages in the process. In particular, variations in the cell-line or the cell culture can alter the structure of the final protein. For instance, a major biotherapeutic in use is recombinant human (rh) erythropoietin (EPO), which is used to treat renal conditions. The presence of four particular chemical groups on the protein EPO will cause the EPO protein to increase. This is due to a decrease in the clearance and an increased level of activity. This has clinical implications and alters the amount of substance, which would be used in individuals. In fact, recent analyses of biosimilar EPO products found that the composition of different batches varied greatly.
INDIAN SCENARIO
There have been early successes that can provide the motivation with Bharat Biotech producing the first biotherapeutic molecule from India and the first protein against staphylococcus infection. It has received a global patent for Lysostaphin, which works on staphylococcus infection. The market potential is $12 billion. The biotechnology industry is currently a colossal melting pot of many ascendant technologies, including molecular biology, pharmacogenomics, biotechnology, tools, genomics, proteomics, bioinformatics, nanotechnology, telemedicine, electronics, fibber optics and computerisation. The gelling of the industry offers new approaches to the discovery, design and production of drugs, vaccines, medical devices and diagnostics.
For India, the issue is production facilities and it is important for the country to develop a manufacturing base. A manufacturing base is neither patentable nor reproducible. What is also needed is an interdisciplinary approach, which is the beauty of the biotechnology field and without which there would be no Lysostaphin.
Simply speaking, the biotherapeutic business features generic biotherapeutics that is a pre-genome business and new biotherapeutics that is a post-genome. The question is how much is one lagging behind, even with pre-genomic biotherapeutics. There are multiple approaches to biotherapeutics. Natural products can be biotherapeutic. So can stem cells, improved and modified vaccines, proteins, genes and monoclonal antibodies. Not just protein alone. One has to look at the bigger picture.
(The author is with Accure Labs Pvt. Ltd, Noida)