Prominent Reasons Behind The Failure Of NAMPT inhibitors And Key Strategies Adopted By Developers To Overcome Such Challenges

NAMPT inhibitors are a class of drugs that target the enzyme nicotinamide phosphoribosyltransferase (NAMPT). This enzyme plays a crucial role in the production of nicotinamide adenine dinucleotide (NAD+), a molecule that is essential for cellular metabolism. NAMPT inhibitors work by blocking the activity of NAMPT, which in turn reduces the production of NAD+. NAD+ is involved in a wide range of cellular processes, including energy metabolism, DNA repair, and gene expression.  There are several types of NAMPT inhibitors, including small molecules, peptides, and antibodies. Small molecules are the most commonly used type of NAMPT inhibitor, as they are relatively easy to synthesize and can be administered orally. Despite their potential therapeutic benefits, NAMPT inhibitors have faced several challenges in clinical development. One of the main challenges is the development of drug resistance, as cancer cells can develop mechanisms to bypass the inhibition of NAMPT. Additionally, NAMPT inhibitors can have off-target effects, which can lead to toxicity and adverse side effects.

Challenges Faced by NAMPT Inhibitors

NAMPT inhibitors have emerged as a promising target for the development of therapies against a range of disease indications, especially, the different forms of cancers. Several trials focused on evaluation of such drugs were discontinued in the past. However, despite initial optimism, the development of these inhibitors has faced significant challenges. Several factors have contributed to the failure of NAMPT inhibitors in clinical trials, including poor pharmacokinetic properties, limited efficacy, and toxicity issues. We, here at Roots Analysis, developed a proprietary analysis that examined the reasons behind the failure of such drugs. As a starting point, the information on terminated, suspended and withdrawn trials was collated from and PubMed using relevant search keywords. The failed drugs were then analyzed based on various parameters, such as phase of discontinuation, trial status of discontinuation, target indication, route of administration, type of molecule and reason behind failure. Below, I have pasted a few figures from the analysis.

The first-generation NAMPT inhibitors failed to achieve desirable objective responses, and exhibited dose-limiting toxicities and poor PK properties in clinical trials.

As can be observed in the first figure, majority (50%) of the trials were discontinued in phase I stage of their study; notably, none of the trials reached past phase II stage. It is worth mentioning here that solid tumors (including several types of lymphoma and melanoma) emerged as the most targeted group of indications by drugs that failed to pass the trials. Interestingly, thrombocytopenia was seen as the most significant dose-limiting toxicity, along with gastrointestinal toxicity; these two emerged as the most prominent reasons for drug failure.

Below, I’ve provided brief overview of the prominent reasons for NAMPT inhibitors drug failure:

  • Thrombocytopenia: Thrombocytopenia, or a low platelet count, is a common side effect of NAMPT inhibitors. Platelets are essential for blood clotting, and a low platelet count can lead to bleeding and other complications. Thrombocytopenia is a significant dose-limiting toxicity for NAMPT inhibitors, and its prevalence has been a major factor in drug failure.
  • GI Toxicity: Gastrointestinal (GI) toxicity is another common side effect of NAMPT inhibitors. GI toxicity can manifest as nausea, vomiting, diarrhea, and other symptoms, and can significantly impact patient quality of life. GI toxicity is also a significant dose-limiting toxicity for NAMPT inhibitors, and its prevalence has been a major factor in drug failure.
  • Lack of Drug Efficacy: Despite their promise, NAMPT inhibitors have also faced challenges in demonstrating efficacy in clinical trials. This lack of drug efficacy has been a significant factor in drug failure, as it has prevented NAMPT inhibitors from receiving regulatory approval. Researchers are continuing to investigate the mechanisms of action of NAMPT inhibitors and are working to identify ways to improve their efficacy.
  • Lymphocytopenia: The prevalence of lymphocytopenia, a condition characterized by a low lymphocyte count, has been a major factor in the failure of NAMPT inhibitors due to its substantial dose-limiting toxicity.
  • Financial Constraints: Financial constraints have also played a role in the failure of NAMPT inhibitors. Developing new drugs is a costly and time-consuming process, and many promising drugs fail to make it to market due to financial constraints. NAMPT inhibitors are no exception, and the high cost of drug development has been a significant factor in drug failure.

Overcoming Obstacles: Companies’ Initiatives for NAMPT inhibitor

In order to ameliorate their proprietary candidates, drug developers are actively exploring diverse approval strategies. Many of the developers are carrying out various innovations in order to skip past the reasons for drug failures of NAMPT inhibitors, depicted in the above analysis. Below, I have pasted the key strategies adopted by such prominent developers to target key reasons for the failure of NAMPT inhibitors in clinical studies.

Key Strategies adopted by such prominent developers to target key reasons for the failure of NAMPT inhibitors in clinical studies.

Proprietary Approach of Roots Analysis: Key Strategies for Successful NAMPT Inhibitors Development

Using our proprietary approach, we identified several key parameters / strategies related to the successful development of NAMPT targeting therapeutics. As a starting point, we determined the general reasons for failure of trials focused on NAMPT inhibitors, through reliable secondary sources. We then attempted to identify the key strategies adopted by drug developers to ensure the success of their candidates. Further, we identified the key parameters / strategies that, we believe, are likely to have a significant impact on the FDA approval of NAMPT inhibitors. Based on our proprietary scoring criteria and secondary research, scores were assigned to each of the key parameters which were then used to calculate the final output score. Below, I have pasted wind-rose charts for each of the drug candidates, highlighting the predominant business models adopted by the players engaged in this market space to expedite the FDA approval.

we determined the general reasons for failure of trials focused on NAMPT inhibitors, through reliable secondary sources. We then attempted to identify the key strategies adopted by drug developers to ensure the success of their candidates.

Promising Outlook: NAMPT Inhibitors Shows Potential Despite Drug Failures

Despite several drug failures in recent years, the NAMPT inhibitor domain shows promise, due to the key strategies adopted by leading developers. Many of these developers have taken targeted initiatives to improve the therapeutic qualities of failed candidates, offering hope for continued growth in the coming decade. While the challenges faced by NAMPT inhibitors in clinical development are significant, developers are taking a proactive approach to overcome them. By identifying and addressing the specific issues that have led to drug failures, developers are working to improve the efficacy and safety of NAMPT inhibitors. These targeted initiatives include improving dose-limiting toxicities, such as thrombocytopenia and lymphocytopenia, as well as enhancing drug efficacy and addressing financial constraints. By taking a tailored approach to clinical development, developers are increasing the chances of success for NAMPT inhibitors.

For detailed insights about this domain, check out our report on NAMPT Inhibitor Market

About Author


Ronit Sharma is an accomplished business research and competitive intelligence professional with over six years of experience in the pharmaceutical and healthcare industry. As a team leader at Roots Analysis, he has authored numerous multidisciplinary market research reports, and led the efforts on several bespoken consulting assignments, providing valuable insights into the latest innovations in healthcare and the digital transformation of the pharmaceutical industry. Ronit’s exceptional analytical skills and strategic thinking in the field contribute to the firm’s intellectual capital, empowering clients to make informed decisions in the dynamic pharmaceutical landscape. With a passion for staying at the forefront of industry advancements, Ronit specializes in identifying emerging opportunities for various stakeholders, leveraging his deep understanding of market trends and technological developments. He is committed to fostering an environment of excellence, creativity, and innovation within his team, encouraging collaboration and empowering team members to bring their best ideas to the table.

Recently, Ronit’s expertise has been recognized by the online news agency, where he was interviewed and featured as an emerging industry leader. Ronit holds a B. Tech degree in Biotechnology from Lovely Professional University and his research and thought leadership can be found in his professional blog and social media profiles, where he shares the latest insights and engages in meaningful discussions with industry peers. To ensure the highest ethical standards, Ronit openly declares no conflicts of interest in his work, ensuring unbiased and trustworthy contributions. His insights undergo rigorous editorial and peer-review processes, establishing his credibility as a thought leader within the pharmaceutical and healthcare domain. Ronit’s exceptional analytical and strategic thinking skills, coupled with his commitment to excellence, make him a valuable asset to any organization in the pharmaceutical and healthcare industry.