Repurposed Drugs vs. Novel Drugs: Which are Better and Why?

Repurposed Drugs vs. Novel Drugs: Which are Better and Why?: Drug repurposing (also known as Drug repositioning) is a strategy for discovering new uses for approved/investigational drugs that are beyond the scope of the original medical indication. This approach offers several advantages over developing a novel drug for a given indication. Various data-driven and experimental approaches have been recommended for the identification of drug candidates that can be repurposed. However, there are some major regulatory as well as technological challenges that need to be addressed.

Advantages of Repurposed Drugs

Notably, the drug repurposing approach benefits from the fact that approved medicines and several discarded compounds have already been tested in humans and comprehensive information is available on their pharmacology, dose, possible toxicity and formulation, etc. Drug repurposing has numerous advantages over the conventional drug discovery approaches including:

  • The approach considerably reduces the R&D costs.
  • Reduces time of drug development as various existing compounds have already demonstrated safety in humans, it does not require Phase I clinical trials.
  • Potential for reuse despite evidence of adverse effects and failed efficacy in some indications.

Popular Approaches for Repurposed Drugs

Drug repositioning has now become a significant part of the pharmaceutical industry. There are several drugs that have been or are currently being repurposed for novel indications. Repurposing/repositioning occurs through different stages of drug development and approval. Some of the popular approaches for drug repurposing include:

1, Repurposing Oncology drugs

The drug repositioning/recycling approach has actively and effectively been taken up by the researchers and pharmaceutical industry, especially in the oncology domain. Drugs in the oncology domain are originally developed for a particular cancer type. However, they can undergo clinical trials in other similar tumor types, producing versatile drugs.

Cancer appears appropriate for repurposing drugs as a single mechanism or biomarker is frequently linked to a broad range of tumor types. One prominent cancer immunotherapy is Merck’s Keytruda (pembrolizumab) which was first approved for advanced melanoma. Today, it is approved for 14 cancer types, including lung cancer and lymphoma. The company is constantly evaluating Keytruda for more cancer types, such as triple-negative breast cancer, etc. Notably, Keytruda is a programmed cell death-1 (PD-1) inhibitor which acts by blocking the PD-1 receptor and its interaction with ligands which helps to activate a T-cell mediated immune response against tumor cells. Due to its similar PD-1-based mechanism of action (MOA), Bristol-Myers Squibb’s (BMS) Opdivo is approved for 10 cancer types and continues to investigate the drug in other oncology indications.

2.  Repositioning Drugs across Therapy Areas

Apart from repositioning drugs within disease areas, the pharmaceutical industry is evaluating whether drugs approved within one disease area can benefit patients in another therapy area. It is common knowledge that oncology is a major therapy area in the pharmaceutical industry. Therefore, non-oncology drugs are often repurposed to treat cancers. For instance, experiments have demonstrated that clarithromycin is effective in H. pylori-associated cancers such as mucosa‐associated lymphoid tissue (MALT) lymphoma. Furthermore, studies have proven its efficacy in other cancer types, including multiple myeloma and chronic myeloid leukemia (CML). The main mechanisms by which clarithromycin exhibits anti-cancer properties are prolonged reduction in pro-inflammatory cytokines, anti-angiogenesis and inhibition of autophagy. This antibiotic’s efficacy in cancer is improved when it is combined with existing cancer drugs targeting other aspects of tumor activity.

3. Aspirin: The Versatile Drug

Aspirin (acetylsalicylic acid) is a powerful drug that is not only being evaluated in oncology but also in cardiac-related indications such as heart attacks. Studies show that low doses of the drug reduce the risk of developing a broad range of cancer types, including colorectal and pancreatic cancers.

4. Repurposing Oncology Drugs for Other Therapy Areas

Studies have proved that oncology drugs can also be repurposed for indications other than cancer. For example, Novartis’ Arzerra (Ofatumumab) is a monoclonal antibody which targets the CD20 protein and was initially developed to treat chronic lymphocytic leukemia (CLL). However, many experiments have demonstrated clinical benefits with anti-CD20–mediated B-cell depletion in clinical studies of patients with MS.

5. Repositioning Drugs for Rare Diseases

It is common knowledge that there are only a few therapeutic options for rare diseases as these diseases affect only a small percentage of the overall population. Drug repurposing can significantly reduce the R&D cost and be groundbreaking for patients with rare diseases. For instance, rapamycin was developed as an anti-fungal drug initially. However, after the discovery of its immunosuppressive properties linked to its inhibition of the mTOR protein kinase, Pfizer’s Rapamune was approved to prevent organ transplant rejection. Also, it became the first drug approved for lymphangioleiomyomatosis (LAM), a rare genetic lung disease.

6. Latest Use of Repurposed Drugs for COVID-19

Drugs are also being repurposed for COVID-19, the current global pandemic. Popular drugs that are being evaluated for the disease include AbbVie’s Kaletra and Ascletis Pharma’s Ganovo plus ritonavir & other combinations which have demonstrated three COVID-19 recovered cases each. Furthermore, Gilead Pharmeceuticals’ Remdesiver has shown no adverse events in COVID-19 patients and has shown to be effective in some cases.

Way Forward

Due to soaring drug prices and the slow pace of drug discovery and development, repurposing existing drugs to treat diseases other than the indicated diseases is gradually becoming an attractive proposition. It not only involves the use of compounds with lower overall R&D costs but also helps shorten the development timelines of drugs. Given the pace of drug development through repurposed approach, such drugs will soon capture a significant portion of the pharmaceutical industry.

-Harsha Agarwal (Life Sciences) and the Editorial Team

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