The global health landscape is increasingly challenged by obesity, ranked by the World Health Organization as the third largest global health threat behind smoking and war. This condition significantly elevates the risk of devastating conditions like hypertension, arthritis, diabetes, and even some cancers. Recognizing the urgent need for effective treatments beyond invasive bariatric surgery and the often-ineffective "eat less, move more" mantra, pharmaceutical companies like Novartis have ventured into developing weight loss drugs. This article delves into Novartis' history in weight loss drug development, with a particular focus on LIK066, its clinical trials, and the role of public contributions in its research and development (R&D).
The Patient Perspective: A Driving Force
Novartis, recognizing the limitations of existing weight loss treatments, adopted a patient-centric approach in developing LIK066. This involved partnering with patient advocacy groups like the Obesity Action Coalition to gain insights into the needs and challenges faced by individuals with obesity. James Zervios, now vice president of marketing and communications at the Obesity Action Coalition, experienced firsthand the difficulties of weight loss. His personal journey of losing 65 pounds after a doctor's ultimatum, coupled with his advocacy work, highlighted the need for effective and respectful treatment options.
This patient-centric approach influenced various aspects of the LIK066 clinical trial, from the language used in study materials to the way the trial was marketed. For example, the study was referred to as a "weight loss trial" rather than an "obesity trial," and promotional materials avoided dehumanizing depictions of individuals with obesity.
LIK066: From Discovery to Discontinuation
The story of LIK066 began with a collaborative effort led by Will Chutkow, a cardiologist at the Veterans Affairs (VA) Medical Center in Boston and a researcher at the Novartis Institutes for BioMedical Research (NIBR). Chutkow initiated a "summit" of researchers across NIBR to identify potential drug targets for weight loss. This collaborative approach led to the identification of a compound, LIK066, designed by Novartis chemist Greg Bebernitz in collaboration with researchers at Advinus Therapeutics to block two proteins involved in absorbing sugar in the kidneys and intestines.
Interestingly, LIK066's potential for weight loss was initially observed as a side effect in an early-stage clinical trial for type 2 diabetes. This serendipitous finding prompted Novartis to conduct a new early-stage clinical trial specifically for weight loss in patients with obesity. While the early-stage trial showed promising results, with patients experiencing mild diarrhea and unexpected weight loss from a once-daily dose, the journey of LIK066 took an unexpected turn.
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Despite early Phase II data showing a positive dose response, the magnitude of weight loss achieved with LIK066 as a monotherapy was deemed insufficient to deliver transformational benefit to patients, especially considering the evolving marketplace and available treatment options. Consequently, Novartis made the difficult decision not to proceed to Phase III with the current program and began closing selected clinical studies according to standard regulatory protocols.
The Role of Public Contributions in Novartis' Drug Development
Novartis' pursuit of innovative treatments extends beyond LIK066, and a significant aspect of its drug development history involves public contributions. A study analyzing Novartis' products approved by the European Medicines Agency (EMA) between January 2014 and May 2024 revealed the extent of public funding in its R&D efforts.
Out of the 25 new products approved during this period, 16 were acquired, licensed, or co-developed, highlighting Novartis' reliance on external innovation sources. Notably, six products were acquired from academic spin-outs, one from a publicly funded research institute, and two were co-developed with publicly funded hospitals or universities.
Overall, 44% of Novartis' products approved between 2014 and 2024 benefited from public support through government grants, academic collaborations, or public institutions. These contributions were primarily concentrated in the earlier stages of R&D, including basic, applied, and translational research, as well as technology transfer support to university spin-outs.
The analysis also revealed a correlation between public funding, acquisition strategies, and therapeutic innovation. Products with documented public contributions tended to demonstrate better therapeutic value assessments, as measured by French ASMR ratings. Acquired or licensed products also showed a tendency toward higher therapeutic value.
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Examples of Publicly Supported Products
Several specific examples illustrate the role of public funding in Novartis' drug development:
- Kymriah®: The exclusive licensing right for this product was acquired from the University of Pennsylvania.
- Luxturna®: Spark Therapeutics, a spin-out from the Children’s Hospital of Philadelphia, co-developed this drug with the University of Pennsylvania.
- Zolgensma®: AveXis (acquired by Novartis) licensed this product from the National Children’s Hospital, the University of Pennsylvania, and ReGenX Biosciences. James Wilson at the University of Pennsylvania received over $35.8 million in funding from the NIH for research related to adeno-associated virus, which was pivotal in the development of the technology.
- Lutathera®: Supranational and national funding supported the development of this drug, which was acquired by AAA.
- Rydapt®: National funding from the University of Rotterdam supported the startup researchers who developed the drug. Phase 1 trials were carried out in Erasmus MC with national funding.
Novartis and Novo Nordisk: A Comparative Analysis
A comparative analysis of Novartis and Novo Nordisk, two of Europe's fastest-growing pharmaceutical companies, reveals distinct approaches to product development and the utilization of public funding. While both companies have benefited from public contributions, Novartis relies more heavily on acquisitions and licensing agreements compared to Novo Nordisk, which predominantly advances its products through internal R&D efforts.
Between 2014 and 2024, Novartis had a significantly higher number of newly approved products compared to Novo Nordisk (25 vs. 6). A more significant proportion of Novartis' products were either acquired, licensed, or co-developed (64% vs. 33%), and a higher percentage benefited from public contributions (44% vs. 16.6%).
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