MRD Pharma Consultancy
Mohamed Dewji has more than 30 years of international pharmaceutical industry expertise in clinical development and medical affairs. He has directed clinical development in oncology at several pharmaceutical companies including AstraZeneca, Novartis, GSK and Pfizer. During his time in industry he led clinical trial design and execution across all phases of oncology drug development and has extensive experience in novel therapeutics, for both exploratory and late stage clinical development.
Section 1: Response to COVID-19
1.1. How have pharma R&D priorities shifted in response to COVID-19?
If you look across all therapeutic areas in terms of drug development right now, clearly the one therapeutic area that continues to be head and shoulders above the rest is oncology. I think one of the largest impacts the COVID-19 pandemic has had has been its impact on not only cancer clinical trials but also how cancer is managed as a disease. It has been one of those therapeutic areas that have been relatively resource-intensive and, therefore, traditionally meant patients were admitted to medical facilities or hospitals for regular visits. The impact of COVID-19 has been on how those patients are managed.
I think several things will emerge. From a pharma perspective globally, the focus on drug development will certainly continue, but perhaps it will be one that progresses in a more patient-centric fashion.
Consider, for example, an oral therapy as opposed to an IV. Using an oral therapy means that the patient does not have to come into a clinical setting and be there for half a day or a whole day to receive their treatment and required monitoring before they can go home. If they can receive that in the comfort of their own home and have that managed through a tertiary care network of nurses or experts who can come and do the blood draws to monitor the patient, then that is desirable and is going to become increasingly relevant.
That said, there is a huge focus right now on areas like immunotherapy, which is not going away. It is certainly here for the long run and I think that it has established its foothold in pharma in a way that 20 years ago would have not been possible as we did not understand the intricacies of the immune system the extent we do now.
Immunotherapy allows us to think more rationally about how we can address challenges such as the COVID-19 pandemic. There may potentially be some things that come out of the work being done on cancer patients and cancer therapy that could be beneficial to the way that we can treat patients with COVID-19 as well.
1.2. What new R&D tools have pharma companies adopted for clinical trials? Which of these tools will stay with us post-COVID?
I think the decentralization of clinical trials and/or the fact that clinical trials have been going digital for a long time. When I first started in the business, case report forms were on a three-part NCR paper. We have gone through the whole electronic CRF piece where you can complete your monitoring visit before actually going on-site and checking key data against source documentation.
I think we will see the entire process become completely digitized resulting in a minimal requirement for people to go to a clinical site from a trial perspective and look at the documentation. That is not to say that audits cannot take place. In the current climate, it is very sensible to try to minimize the number of people that are coming into a hospital, not for a specific treatment.
I think one of the things that a lot of companies running clinical trials in the current climate are trying to accommodate is adapting protocol designed to incorporate elements such as telemedicine and digital visits. It is increasingly important to provide tools like a patient’s quality of life assessments and other processes that can be done online so the patient does not have to come into the clinical setting. Another example is having safety assessments through weekly follow-ups with trial coordinators or trial nurses.
I think the speed of that change has been forced upon the industry by this COVID-19 challenge. Some of these changes were coming anyway, but the fact that we have the tools now and people are adapting those tools to try and make everything work is incredibly important.
The other positive piece that goes alongside this is the fact that regulators are also appreciating that pharma companies are doing their best to manage trials in these difficult circumstances. They are also guiding in terms of how to mitigate that risk, which is all about ensuring you continue to maintain the necessary risk-benefit in favor of the patient. Right now, for many patients, if they don’t need to come into a clinical center or a hospital, then that risk-benefit is in their favor to stay at home provided that they can be monitored.
1.3. How are health bodies, such as the EMA, FDA, and NICE, looking to cooperate with pharma R&D?
I think the relationship between health bodies and pharma has always been open. Obviously, in the current environment, I think it is about looking again to see whether we continue to take new therapies forward, whilst ensuring we uphold the levels of safety and efficacy we would want from a new medicine under normal circumstances. So, it’s about being pragmatic in these circumstances.
What I see is very much a partnership between pharma, regulators, payers, but also within the academic community with physicians and experts trying to find appropriate solutions to make sure that you can continue to provide the best possible care for your patients. One thing we have seen, specifically in terms of the cancer therapeutics, is the difficulty that some of these patients have because they are unfortunately prone to infection due of the nature of their disease, and also the nature of the therapies that they receive as a consequence of trying to treat cancer.
Data from China and Italy suggests that around 20% of all fatalities from COVID-19 are in patients who have some underlying cancer or cancer comorbidity or that have had cancer in the past. This group of patients is particularly vulnerable to the disease and, therefore, the way that oncologists and other physicians are involved in looking after these patients has to adapt and adjust to take that into account.
Overall, I see a couple of trends right now. We can split the clinical development piece into early clinical trials – phases one and two through to proof of concept – and of late-stage trials at the other end of the scale, where you are generating data primarily for regulatory approvals. If we consider phase one trials with a first-in-human early evaluation of novel therapeutics, the challenges are somewhat more daunting than late-stage trials because these trials typically tend to be fairly complex, usually relying on patients being in the hospital sometimes for some time to enable multiple types of blood draws. The patients may undergo several biopsies and, therefore, the complexity of some of those early trials may have to be trimmed back just to manage the risk-benefit for patients.
1.4. What role has been played by new stakeholders in the pharma R&D environment?
If you look at digital companies such as Amazon and Google, their overall currency is the data they generate around what the population is doing. That data from a patient’s perspective could potentially be incredibly important as part of a clinical trial. For example, if you have patients with cancer who have completed their treatment, then you might see that patients who take part in regular exercise tend to generally have better outcomes and better overall long-term survival outcomes than patients who do not.
We can ask whether this an area where some of these new tech providers can come in? As they find ways to better motivate patients to keep as healthy as possible, I think we can expect to see new partnerships being developed in that area. Moreover, more companies are realizing that with a better, broader understanding of health data, mobile apps can be developed for individual trials, which allow a lot of patients to be managed remotely as well as providing some really useful data as part of the overall trial process. This is the case only as long as the data is managed within the grounds of personalized data legislation.
Some of these digital tools are going to be able to share information in a way that can potentially help us lead more healthy lives, but I also see some long-term strategic benefits emerging out of this, along with some key lessons. Pharma and healthcare providers will look back and say, “Actually, we were doing things that way before, but we didn’t need to make sure patients got on a train and traveled hundreds of miles to come into a hospital to have an appointment with a consultant when they could have done it via Skype.” I think it all relies on putting appropriate safeguards and legislation in place to protect patient data. Although a lot relies on risk-benefit, you have to also consider pragmatism.
Section 2: Pharma R&D Post COVID-19
2.1. Will there be renewed interest in infectious diseases? Will this affect pharma companies’ R&D pipelines?
Due to the pandemic, there has been a significant refocusing of energy and resources on areas such as antiviral and anti-infective therapy, which over the past decade have traditionally had been something of a desert within pharma development.
On the vaccine side, there is a huge scramble to develop a COVID-19 vaccine. However, I would temper that by bringing into focus the fact that a vaccine is not a panacea, but it may help to make the disease more manageable. One scenario I potentially foresee is the development of a vaccine, which would have to be adapted and given year on year. As is the case with the flu vaccine that people take on an annual basis, it does not prevent you from getting the flu, rather makes it generally more manageable (depending on which strain is around for that particular flu season). I suspect that we may end up in a similar scenario for COVID-19, namely that COVID is not going to disappear, but is going to be there in the background, and we will find ways to manage it.
2.2. Will cross-industry partnerships, formed during the pandemic, create new “R&D innovation” models?
Certainly, from an oncology perspective, I think that model existed to a great extent. If you look at the level of cooperation that organizations like Cancer Research UK and other groups across the globe have with different pharma partners, those models have been there for many years. I think COVID-19 has brought that into a sharper focus where we can bring the excellence and knowledge that exists in academia together with the expertise of pharma in drug and vaccine development and start to get the two to work cooperatively to address very specific goals and needs.
I think it is a positive sign for what we can do if we put our minds to it, and I think this might be the forerunner for a future model whereby rarer diseases such as Ebola, which found it very difficult to get the level of support from collaborations on this level, will begin to receive greater multi-lateral attention. It’s when the reality of the problem confronts every stakeholder that, suddenly, it becomes everyone’s problem. It forces people to work together in a way that we can address a common problem.
From a pharma perspective, the aim is to try and keep as much of R&D on track as possible. I think we will face some tough situations in the months and potentially years to come because I expect this pandemic makes us rethink our current healthcare model.
For example, we need to start asking ourselves whether we need to keep or bring patients in as much as we are used to doing? Is there a way that we can manage those patients safely in their home environment and provide a level of care that may not be the same as what they have been previously used to, but is fit for purpose at the end of the day? Perhaps this also allows patients to feel much more comfortable about the treatment that they’re receiving.
There is one other thing that I want to add from a cancer perspective. I think if you look at the trends over the last three months, one of the things you will see is that the number of new cancer diagnoses has been decreasing. This is simply because patients have not been coming into the hospital. It is not that the disease has disappeared, but just that it has gone undiagnosed. Sadly, if that continues, it means that we are just storing up that group of patients for a huge tidal wave of new cases, probably with much more advanced disease that needs treatment in the future.
I think one of the challenges healthcare has right now is to continue to engage with people and say, “Actually, if you’re not feeling well, then you need to go and see your doctor. If you have to go to the hospital, then you have to go.” It’s not that you are going to get COVID-19, but there is almost a fear within society that if you go to a hospital, they may get COVID-19.
2.3. What will be the post-COVID-19 impact on clinical trials?
The perception seems to be that there will be an impact because we are seeing so many resources being allocated to try and manage the disease. It is certainly going to be a tough place in terms of how we get things done, but I think from the pharma perspective, one of the trends we have seen is that trials are still being performed. There is a definite focus on Southeast Asia and Australia as there are potentially increased opportunities to get trials done relatively quickly in countries that have not been hit as badly as Europe and North America by the pandemic.
I know several organizations have been evaluating the possibility of running trials in Australia and I know that there are CROs based out there keen to talk up those opportunities and their potential. This will be another interesting to keep an eye on post-COVID to see how everything plays out.
I think several things are going to be firmly established now as part of the routine management of disease, and therefore become part of clinical trials going forward. The first is the telemedicine piece and factors into a broader attempt at the decentralization of routine patient assessments to try to keep patients in their own homes and in an environment where they are less at risk of getting an infection, particularly for therapeutic areas like cancer. This is, of course, a huge challenge, and we must minimize the risk to the patients who are taking part in trials.
This type of challenge has been forced upon everyone, much like working from home. Some companies encouraged people to work from home before, but now, many of us have had to do that whether we like it or not and adapt our lives accordingly. It is going to be very interesting to see how the next few years evolve as far as this space is concerned, but I think clinical trials are certainly not going back to the way they were even a year ago.
2.4. How will source models in pharma R&D change?
In terms of geographical placement and management of CROs, pharma companies traditionally have always looked to manage risk. Several companies I have worked for in the past had pandemic management plans, and this dates back at least 10 years. However, this is not something that everyone has had in place. As part of that, putting trials on hold or working with particular CROs to manage trial locations, moving trials, or conducting trials in particular areas where it may be easier to conduct, is certainly part of that overall risk management process.
Around the point of clinical trial supplies and APIs, a lot of that manufacturing has been done in India or China over the last few years. However, pharma as part of a broader risk management approach will look to make sure there are enough alternative providers. The challenge we have all factors around uncertainty – how long this problem is going to be around for and in what shape or form it’s going to exist?
If we look back in history, a lot of comparisons have been between COVID-19 and the 1918 Spanish flu as it wasn’t the first wave that caused the biggest loss of life, but the second wave that ravaged populations when countries came out of lockdown and restored relative normality only to be met with an increase. I think that is something most governments are very sensitive to. How global pharma manufacturing manages this is clearly a challenge, and so API procurement is part of that overall risk management piece everyone is trying to figure out.