Why Psychedelic Drugs Need Specialist Clinical Research Organisations?
In 2005, in a laboratory at Cambridge University, Professor Steve Jackson was at the helm of a small drug development company called KuDOS. The drug was the first of a completely new drug category, a PARP inhibitor, which looked to prevent cancer cells from repairing by targeting a specific hereditary gene. He had invented it in 1997 but had failed to get approval for the drug for use in patients. The problem was Jackson was struggling to run large complex clinical trials which required significant financial and clinical resources.
Upon the acquisition of KuDOS by AstraZeneca, the clinical trials were accelerated and Olaparib was designated as a breakthrough therapy following FDA’s approval to treat advanced ovarian cancer in 2014. Olaparib became the first cancer drug directed against an inherited genetic mutation and started a new era for personalised cancer treatments. In less than a decade, it went from being a twinkle in a researcher’s eye to being licensed for sale following its successful commercialisation by AstraZeneca. Its success has so far led to the approval of four related drugs for the treatment of several types of cancers, and seven compounds that are currently under clinical investigations for various diseases. If it wasn’t for a small phase 2 trial for women with advanced ovarian cancer, Olaparib was going to be shelved by the company instead of being a blockbuster for a number of years with >$1Bn annual revenues.
Professor Jackson’s story illustrates the need for money, resources, and specialist partners to bring a promising new drug to patients at speed. Finding the right clinical trial partner is not a decision drug developers should take lightly, it is investing in the future of their drug.
Numerous drug developers are now looking at psychedelic compounds not only to address the need for effective mental health treatments for intractable conditions but also for conditions with sub-optimal treatments.
While some companies are trying to tap into conditions with high prevalence but low rate of successful treatments, such as major depressive disorder, others are exploring more niche conditions with very limited treatment options. Derivatives of known psychedelic drugs are also being investigated to reduce undesired side effects and to change the onset or duration of action, whilst ensuring that they can get secure IP over these novel compounds.
Numerous clinical trials will need to be conducted to progress all these existing and novel psychedelic compounds towards the market for similar conditions within a heavily regulated system, which breeds competition and frustration. In such an environment, drug developers are likely to find it challenging to enter a market with a number of unique high barriers.
One such barrier is the regulatory knowledge around psychedelic drugs. Working with drugs controlled under Schedule 1 makes it bureaucratically complicated, slow to operationalise and expensive to carry out. Arduous security concerns and protocols concerning drug storage, reporting and handling, as well as an interconnected licensing and approvals process spanning multiple regulators, such as the Home Office and MHRA here in the UK, can elongate setup and lead times, and greatly reduce the number of eligible trial sites and prescribers.
Regulators’ level of familiarity with psychedelic drugs is not a factor to be ignored. Obtaining approval to carry out research with psychedelic drugs can be more difficult in countries where there is no heritage of psychedelic research. It is common for companies who are headquartered elsewhere to conduct psychedelic clinical trials in countries such as the UK, where similar studies have already been approved and regulators are more informed about the safety profiles and potential of psychedelic drugs. A recent example of this is US-based Deme-Rx who recently had their Phase I/II ibogaine trial approved in the UK.
Once a psychedelic treatment is approved for a trial, gathering the necessary data required for obtaining market approval has its own challenges. Drug developers need to show that psychedelic treatments are more efficacious than the standard of care treatments. If comparative studies show similar efficacy, then psychedelic treatments need to be cheaper to deliver to achieve reimbursement. Due to the number of therapy sessions required, psychedelic treatments will almost always be more expensive than, for instance, prescribing established antidepressants. Conducting clinical trials in a way to best demonstrate superior efficacy to existing standards of care is vital to ensure market approval.
Appropriate therapy expertise and provision across all stages of treatment are vital to be able to demonstrate the efficacy of psychedelic-assisted therapies. These stages include preparation, medication and integration, where the therapist prepares the patient about what to expect, administers the drug and works with the patient to interpret the psychedelic experience to achieve long-term meaningful change. The provision of these requires experience which is not easily found amongst clinicians, and training clinicians to deliver psychedelic treatments is not a commonly available option.
Measuring the efficacy of psychedelic treatments can also be complex and might not be well captured by commonly used methodologies. For example, the recent study comparing psilocybin with escitalopram for depression favoured psilocybin only in secondary outcomes, demonstrating the need to carefully select measures that will capture improvements in patient outcomes, and to power trials accordingly.
Psychedelic science is still discovering the treatment methodologies that work best both for the patient and a clinical environment. Finding a balance between delivering the best outcomes to patients and designing an affordable treatment is tricky and may require the use of innovative technologies to tick both boxes.
For no other drug class in history has set and setting been so important, another challenge that affects the efficacy of these treatments, both within and across different patient groups. The psychological, social, and cultural factors which shape the response to psychedelic drugs constitute set and setting and the environment in which psychedelic therapy is delivered greatly contributes to the psychedelic experience. It’s widely accepted that this could have dramatic impacts on the clinical outcomes patients achieve. Unlike a conventional hospital room, the clinical setting of a psychedelic therapy incorporates a comfortable décor, often with warm lighting and music to put the patient at ease. Such a clinical environment suitable for administering psychedelics is essential but can be expensive, slow to set up, and difficult to standardise.
The unique history of psychedelic drugs and the way they affect the mind challenge both the regulatory system in which these compounds need to progress and the companies which are trying to push them through. A specialist clinical research organisation can facilitate this process for drug developers by offering the regulatory and clinical expertise as well as the physical and technological infrastructure required for more effective and affordable clinical studies. A clinical research organisation with experts who understand the regulatory processes and facilities to carry out trials can significantly accelerate the journey of a psychedelic treatment from its ideation stage to market approval.
Clerkenwell Health is currently the only organisation that can offer this end-to-end service and invites psychedelic drug developers to consider collaboration to advance mental healthcare.
