Drug Repositioning.pptx

Drug discovery is a time-consuming, high-investment, and high-risk process in traditional drug development. Drug repositioning has become a popular strategy in recent years.

1. Drug Repositioning Vishakha Vikram Deshmukh B PHARM VIII SEM ROLL NO. 18 Y.B. Chavan College of Pharmacy Dr. Rafiq Zakaria Marg, Rauza Bagh, Aurangabad

2. Introduction The process of drug discovery involves many stages but can be categorized into three stages namely: lead identification followed by preclinical testing in animals and then clinical trials in humans. In order to avoid such long term process of conventional drug discovery, reverse engineering process is gaining importance. Another alternative in drug development strategy is exploration of drug that have already been approved for the treatment of other diseases and/or whose targets have already been discovered. Drug repositioning can be defined as a process of identification of new pharmacological indications from old/existing/failed/investigational/already marketed/FDA approved drug/pro-drug, and the application of the newly developed drugs to the treatment of disease other than the drug’s original/intended therapeutic use.

3. Synonym terms to Drug Repositioning Drug repositioning: finding new uses outside the scope of the original medical indication for existing drug or developing new indications for existing drug or biologics. Drug repurposing : identification, developing and commercializing new uses for existing or abandoned drugs. Drug reprofiling: reducing the risk and associated with drug development with the advantage that the drug has already undergone preclinical and clinical testing. Drug reformulating: finding ways to modify a formulation to allow a drug to enter a new market. Drug rediscovery: investigating new uses for currently prescribe drugs.

4. Need of Drug Repositioning Saving time: The duration of the discovery phase for a repurposed drug is shorter as safety and toxicology studies have already been assessed in the original indication. Saving cost: It costs approximately US$300 Million to bring a repurposed drug to market representing a saving of about 85% compared to the US$2.6 Billion for a new drug if the cost of failed projects is taken into account. Other reasons: A significant number of drugs are repurposed for rare diseases which attracts many developers due to the incentives. FDA and EMA offend provide incentives in such situations. In addition to a lower cost of clinical trials and a shorter development time, drug repurposing is associated with a higher success rate from Phase II to launch

5. Drug repositioning Approaches and Resources The concept of re-profiling or repurposing a drug is deep-rooted on the grounds of poly-pharmacology that reveals the small print on on-target and off-target proteins through which a drug exhibits both anticipated and untoward effects. Repurposing of a drug is carried out in the following steps: In silico approach Experimental approach All the technologies like genomics, proteomics, transcriptomics, and databases which include drug omics data, disease omics data are interconnected in designing the strategy for a proposal of a drug to be repurposed.

6. Drug Repurposing starts with: Collection of raw data related to disease-drug-targets Establishment of drug-target-disease relationship Support of potential evidence in silico screening techniques Generation of proof of concept Generation of experimental evidence Further the shortlisted compounds pass through clinical trials FDA approval Successful repositioning of drug Computational Techniques in Drug Repurposing

7. Challenges and Opportunities Although much progress in drug repurposing has been made in recent years, regulatory approval is the only aim for a successfully repurposed drug. Many challenges to meeting this goal can be foreseen, from the developmental phase all the way to regulatory approval. Optimization of inclusion and exclusion criteria in selection of target population Achievement within timeline Requirement for robust evidence Lack of funding to commercialize the product Clinical trial feasibility for rare diseases Technical challenges to repurposing drugs Novelty in repurposing

8. Few latest Drug Repositioning examples Drug Original indication New indication Albuterol Exercise induced bronchospasm Prevention of paralysis due to spinal cord injury Bupropion Depression Smoking cessation Digitoxin Cardiac arrhythmias & heart failure Treatment of ovarian cancer. Eflornithine African trypanosomiasis Pneumocystis carinii pneumonia in AIDS patients Finasteride Benign prostatic hyperplasia Hair loss Galantamine Polio, paralysis & anaesthesia Alzheimer’s disease Celecoxib Osteoarthritis & adult rheumatoid arthritis Familial adenomatous polyposis Infliximab Crohn’s disease Juvenile rheumatoid arthritis Heparin Anticoagulant & Venous thrombosis Cystic fibrosis Ketoconazole Systemic fungal infection Nephrotoxicity

9. Drug Original Indication New Indication Leflunomide Arthritis Myeloma Nitroprusside Acute congestive heart failure Cerebral vasospasm Omega-3(n-3) polyunsaturated fatty acids High triglyceride level reduction IgA nephropathy Phentolamine Dermal necrosis Autism Ropinirole Hypertension Restless leg syndrome Sodium thiosulfate Cyanide poisoning Platinum-induced ototoxicity in paediatric patients Topiramate Epilepsy Obesity & irritable bowel syndrome Zidovudine Cancer AIDS Artemizole Allergies Malaria Amphotericin-B Fungal infection Leishmaniasis Sildenafil Erectile dysfunction African sleeping sickness Metformin Type-2 diabetics PCOS Minoxidil Hypertension Hair growth

10. Drug Repositioning strategies for COVID-19 COVID-19 has now been declared a pandemic and new treatments are urgently needed as we enter a phase beyond containment. Developing new drugs from scratch may be a lengthy process, thus impractical to face the immediate global challenge. Here we take a snapshot look at the strategy of drug repurposing that promises to identify antiviral agents for the novel coronavirus disease in a time-critical fashion. Also, a perspective that antiviral combinations with a ‘double hit effect’ may offer the best chance of success and clinical translatability. Repurposing of existing antivirals BSAA combination therapy

11. Conclusion Drug discovery and development is a costly, complex, and time-consuming process, often taking 14 to 20 years and $1 billion-plus in Research and Development costs, with no guarantee of success. The use of drug repurposing such time- consuming and costly process that can be easily overcome. Apart from saving time this technique of drug use also favors the development of research for academics, development of an academic institute-industry relationship. The most important advantage would be to the patient as the drug availability for new disease would be quicker, relieving him of disease-related suffering.

12. Thank you!