DDW Multimedia Editor Megan Thomas observes the 2023 drug discovery landscape, speaking to industry experts and looking at the foundations of 2022 on which next year will lean.
Virtual clinical trials
‘Virtual’ and ‘technology’ are concepts which are readily exchanged in this industry, but these are more than just buzzwords. The overall virtual clinical trials market is currently valued at $7.8 billion, with a projected growth of 14% per annum1.
Hampleton’s, an M&A and corporate finance consultancy for companies which centre around technology, recently published a healthtech report2 which suggests that virtual clinical trials are considered to be the future of drug development, because they provide the technology to decentralise testing and therefore an opportunity to improve recruitment, retention, trial diversity, trial delays and costs.
In early November 2022, two Alzheimer’s drugs were tested head-to-head in a first-ever virtual clinical trial3. In the study, published in PLoS Computational Biology, scientists got one step closer to a breakthrough owing to a first-of-its-kind computer model that successfully simulated a clinical trial evaluating the efficacy of multiple treatments for Alzheimer’s disease. On the back of this alone, 2023 should see us get even closer to a breakthrough in this area. “We’re calling this a virtual clinical trial, because we used real, deidentified patient data to simulate health outcomes,” says Wenrui Hao, Associate Professor of Mathematics at Penn State, lead author and co-principal investigator. “What we found aligns almost exactly with findings in prior clinical trials, but because we were using a virtual simulation, we had the added benefit of directly comparing the efficacy of different drugs over longer trial periods.”
The researchers noted that such virtual trials incorporate numerous evidence-based assumptions regarding disease pathogenesis, therapeutic mechanism, side effects and a host of other factors which could impact the outcome. But Jeffrey Petrella, Professor of Radiology and Director of the Alzheimer Imaging Research Laboratory at Duke University School of Medicine, says: “Despite these limitations, this is the first step towards tailored clinical trials. We’ve shown that this type of model can work. I envision it being used as a precision tool to enhance actual clinical trials, optimising dosages and combinations of drugs for individual patients.”
The Covid-19 pandemic was incredibly disruptive for global biomedical research activities, and clinical trials were not exempt from this. However, it also made great strides in proving the success of these sorts of trials. According to the BMJ: “While necessitated by Covid-19, incorporating virtual design elements within a clinical trial can provide supplementary benefits beyond the current climate. Stephen Hahn, the FDA commissioner, recently supported retaining aspects of virtual trials post-Covid-19, saying: “It could really help us expedite and maybe we get that cycle time even shorter if we use some of these processes moving forward.”4,5,6
Asking the right questions
Norstella is a newly formed company that aims to guide life sciences companies through drug development so patients can access therapies quicker. The five organisations that make up Norstella — Citeline, Evaluate, MMIT, Panalgo and The Dedham Group — deliver answers for strategic decision-making from the clinical discovery process through commercialisation. CEO Mike Gallup says there are many hurdles that prevent patients from accessing life-saving medications, from length of time to market to inefficient clinical trials to post-launch coverage restrictions, and that overcoming these barriers requires that pharma companies ask the right questions and glean data-driven answers at every stage of drug development and commercialisation. He shares some of the questions the industry at large should be asking itself as we move into 2023: “What unmet needs exist today, and what are the opportunities for commercial success? How will a treatment fit into the existing competitive landscape? How do payers manage existing products in this therapeutic area? What considerations affect coverage decisions? How does existing contracting in this space affect physician prescribing patterns? I’ve made it my mission to help pharma manufacturers identify and overcome these barriers to access at every turn, so that together, we can help more patients get the treatments they deserve.”
According to Gallup, a more innovative, accessible marketplace hinges on a better process for bringing life-saving drugs to market. So where to start? He says: “To start, manufacturers need to be making more informed business decisions not only at the point of commercialisation but also during the clinical phases. Let’s take clinical trials, for example. It’s well-known that 80% of clinical trials fail to meet their enrollment goals, resulting in ballooning R&D costs and delays to market. In many cases, patients can’t afford to wait. However, if manufacturers are equipped with the right data and insights to identify potential issues with trial recruitment much earlier, then they can solve for them early on, finding ways to improve recruitment efforts or locate the right subset of patients.”
Looking forward, Gallup identifies the important role of real-world data and data science at every stage of drug discovery and development. He explains that real-world data is a critical mechanism for improving drug discovery and development and says: “Manufacturers can leverage this data in many ways during the R&D and clinical stages, using it to identify unmet needs and prioritise their product portfolios, reduce investment risk, improve clinical trial design and recruitment, and more. Then there’s the commercial stage, where RWD can be used to educate payers to make more favorable coverage decisions, or to support efforts toward a future label extension, among many examples.”
An investment perspective
Cameron Wheeler is a partner on the therapeutics team at Deerfield, an investment firm dedicated to advancing healthcare through information, investment, and philanthropy. Looking back at 2022, Wheeler reflects on the movement and prioritisation across the industry to integrate the latest artificial intelligence (AI) and machine learning (ML) technologies into drug discovery and development workflows, including a number of promising partnerships. He says: “While we still have a long path to optimise the use of in silico tools, progress to date has arguably been better than anticipated.”
In 2023, Wheeler thinks the investment community and the industry at large will continue looking to AI and ML to help shorten drug discovery timelines and improve clinical trial operations. As well as major disease areas such as oncology and inflammation, he believes that areas such as metabolic, musculoskeletal, central nervous system, and other degenerative diseases will enter the arena more prominantly. He says: “The hope is that as our tools continue to mature, they will allow us to better understand the complexity of these historically challenging indications.”
Across the developed world, populations are on the rise and Wheeler says the trends suggest that neurodegenerative and metabolic diseases are growing issues for the general population that, without intervention, have the potential to put strain on our healthcare systems. As such, a need for better understanding of the science behind these conditions and actionable treatments is critical.
Wheeler thinks a continued push into the mainstream for clinical trials, digital trends and an efficiency focus. He says: “Progress will need to be done deliberately as industry works to solve the many regulatory challenges expected to arise. In the near term, as we’ve seen in oncology, we will benefit from new access to important genetic and biological information to not only select patients who will best respond to test therapies, but also more accurately measure the effect of a test therapy in a disease.”
Wheeler concludes: “These exciting benefits in 2023 are still being realised and there remain challenges in determining the most effective ways to use this data to inform and measure trials so that we can ultimately find the right patients for the right therapeutics. Broader than a specific disease, another particularly exciting trend is our increasing perception of medicine and the scientific process among the general population. Largely attributable to the Covid-19 vaccine efforts, this trend is expected to lead to greater participation in clinical trials and in turn, more diversity and broader representation across clinical studies.”
The future of psychedelics
In a recent episode of the DDW podcast, DDW spoke with Dr Mark Varney, the Chief Scientific Officer at PsychoGenics, who discussed both his and the company’s work on CNS drug discovery. In the interview, Varney commented, among other things, on what he considers to be a particularly exciting future for psychedelics: “Psychedelics are being evaluated in a scientific, well-controlled manner and I think it will be important to see the outcome of these results as to whether psychedelics can play an important role in some aspects of the treatment of mental health disorders.”
Looking further into this, there is no doubt that research into psychedelic substances is moving into the mainstream, exemplified through companies such as Psylo, an Australia-based psychedelic biotech focusing on psychedelic-inspired medicine to treat mental illness, as well as Clairvoyant, who DDW reported in July 2022 as having begun a Phase II magic mushroom molecule psilocybin study in Canada for alcohol use disorder, as well as targeting the clinical validation of psilocybin in the EU, the UK, and Canada.
Moreover, a new multicentre clinical trial, published on 3 November 2022 and led by COMPASS Pathways across 22 international sites, including the Institute of Psychiatry, Psychology & Neuroscience (IoPPN) at King’s College London and South London and Maudsley NHS Foundation Trust, has found that a 25mg dose of psilocybin, alongside psychological support, had a significant impact in reducing symptoms of depression in participants with treatment-resistant depression10. This is the largest clinical trial of this nature to date. With these foundations in place, 2023 looks promising for psilocybin and psychedelics research at large.
According to PsychedelicHealth8, this sort of research is ‘creating optimism about the potential efficacy of psychedelic drugs as an alternative or supplement to traditionally manufactured pharmaceuticals to treat depression, anxiety, and addiction among other mental health conditions’. Further evidence that the industry is really starting to take psychedelics seriously is that a new peer reviewed journal, Psychedelic Medicine, will be launched in 2023 to provide a scientific forum for original research papers8.
Nature points out that Oregon will be a region to watch as it becomes the first state with widely legalised psychedelics9. In January 2023, following a ballot measure in 2020 in which voters called on the state to begin creating the infrastructure needed to make psilocybin available as a treatment for mental-health disorders such as depression and anxiety, Oregon will begin its much-anticipated real-world experiment in psychedelic medicine. According to Nature, Canada made a similar move in January 2022, ‘albeit with far more restrictions, allowing designated clinicians to prescribe psilocybin to people with debilitating mental illnesses, such as severe, treatment-resistant depression’.
Start-ups, the economy and funding
Start-ups are becoming increasingly important across drug discovery and development, which is unsurprising when the industry centres around innovation and pushing boundaries. Dr Michael Salako, Investment Director at Start Codon, says that the first and arguably most impactful challenge start-ups and early-stage companies will face in 2023 is the limited access to capital, highlighting the faltering private investment landscape as well as the effects of inflation. He says that these have led to many early-stage companies facing a cash-flow crunch and gives the example of how inflation is leading to talent recruitment and retention issues, as people look for higher salaries to deal with the increased cost of living. He adds: “If a company is outsourcing services, it might also encounter increased costs due to the knock-on effect of inflation on materials and shipping, in addition to increased salaries. This is impacting costs for early-stage companies, which may be pre-revenue or haven’t factored in such added expenses. To deal with these issues, companies are having to expend more capital than planned, consequently leading to them having to raise funds sooner than expected.”
Despite the fall in new investments and the subsequent difficulty of raising funding in the current inflationary macroeconomic environment, Salako thinks that raising capital will be easier for start-ups than it is for later-stage companies seeking multimillion fund raises on account of early-stage companies typically requiring less capital to maintain growth. He says: “From an investor’s point of view, an early-stage company executing on a business plan is not immediately constrained towards trying to exit via an IPO or merger and acquisition against a backdrop where the markets are negative for either option, an option a late/growth stage company, who has undertaken multiple fundraises and has a monthly cash-burn of hundreds of thousands to multi-millions per month, may be desperately seeking. It is however worth noting that investors are being more particular in terms of which companies they choose to invest in.”
Salako says to best prepare for what 2023 holds, start-ups need to focus on building strong, experienced teams and generating quality, commercially relevant science in order to be viewed as being more likely to survive an economic downturn and emerge successful. He says: “With the cost-of-living crisis, employees are being forced to rethink their roles and explore other career opportunities. Seeking more freedom, flexibility and financial opportunities, entrepreneurship is becoming an area more people are starting to turn to. There is currently a lot of support and upskilling opportunities for aspiring entrepreneurs and start-ups. At Start Codon, we are receiving an increasing amount of interest from entrepreneurs and some exciting early-stage companies.”
Following market stabilisation, Salako expects to see some high-value, differentiated companies emerging, comprised of strong, multidisciplinary, diverse teams. He concludes: “There is a bright future ahead for companies that can weather the current storm.”
DDW Volume 24 – Issue 1, Winter 2022/2023
References
- https://www.merckgroup.com/en/research/science-space/envisioning-tomorrow/precision-medicine/generativeai.html
- https://www.hampletonpartners.com/reports/healthtech-report/
- https://medschool.duke.edu/news/two-alzheimers-drugs-tested-head-head-first-ever-virtual-clinical-trial
- de Paula BH, Araújo I, Bandeira L, Barreto NM, Doherty GJ. Recommendations from national regulatory agencies for ongoing cancer trials during the COVID-19 pandemic. The Lancet Oncology. 2020; 21 (5): 624-627.
- Marra C, Chen JL, Coravos A, Stern AD. Quantifying the use of connected digital products in clinical research. NPJ Digital Medicine. 2020; 3 (1): 1-5.
- Baumann J. Clinical Trial Tweaks Forced by Virus Should Stay, Hahn Says. Available from: https://news.bloomberglaw.com/pharma-and-life-sciences/clinical-trial-tweaks-forced-by-virus-should-stay-hahn-says
- https://www.reportlinker.com/p05777316/Global-Oncology-Market-Forecast.html?utm_source=GNW
- https://psychedelichealth.co.uk/2022/05/05/peer-reviewed-psychedelics-journal-2023/
- https://www.nature.com/articles/d41586-022-02872-9
- https://www.kcl.ac.uk/news/largest-trial-to-date-shows-that-psilocybin-reduces-depression-symptoms
