In a recent virtual town hall meeting hosted by BIO, two key leaders from the US FDA laid out how their organisation has adjusted in the wake of the COVID-19 crisis, at what stage of development diagnostics and therapeutics for the virus are, and the pandemic’s long-term effects – both positive and negative – may be on the FDA’s work and on how the pharma industry organises itself.
Taking part in the discussion on June 11th 2020 were Peter Marks, director of the Center for Biologics Evaluation and Research (CBER) at the FDA and Peter Stein, director of the Office of New Drugs (OND) under the Center for Drug Evaluation and Research (CDER). Hosting the talk was Richard Pops, chairman and CEO of Alkermes.
Personnel and Resource Shifts
Bother Marks and Stein noted that the COVID-19 crisis has fundamentally shifted priorities at the FDA, with greater efforts needed to help drive forward therapeutics and vaccines development more vigorously than before. This evolved into Operation Warp Speed, a public–private partnership initiated by the US Federal Government to facilitate and accelerate the development, manufacturing, and distribution of COVID-19 vaccines, therapeutics, and diagnostics.
Personnel changes have followed, with Janet Woodcock, CDER’s director, stepping away from her FDA responsibilities as a regulator to dedicate herself to the Operation Warp Speed efforts in therapeutics, including both at CBER and CDER.
While noting the potential conflict between being a regulator and helping push forward the development of new products, Marks – who has continued in his role at CBER – pointed out the FDA’s vital role in this process, stating that with a number of new vaccines coming through, “providing advice to those programs from a regulatory perspective is going to be critical”
New Therapeutics: Working Together
While the massive mobilisation from the biopharma industry to develop new therapeutics and vaccines is, in many ways, encouraging, it has the potential to be very chaotic. Pressed on this question, Stein asserted that the FDA is “Working to make sure there is a cohesive approach to selecting the drugs that go through to trials.”
It has been great to see industry, academics, NIH and us (the FDA) all come together in a collaborative way
Key to this approach is the new Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV) partnership with the National Institutes of Health (NIH) and the Foundation for the NIH (FNIH) along with a host of other stakeholders from industry and government. Stein was keen to state that the consortium has already made tremendous progress in terms of developing strategies for drug therapeutics. An extensive effort over a short period of time has seen a number of candidates now moving towards the development phase. “It has been great to see industry, academics, NIH and us (the FDA) all come together in a collaborative way,” he exclaimed.
On a similarly positive note, Marks added that “One of the positive things coming out of this situation is the dialogue that has been opened up between industry, academia, and government. All of this collaboration and cooperation will take us where we need to get to together.”
Finding the Priorities
In such a time-sensitive environment, there is a danger that speed is prioritised over efficacy for COVID-19 treatments. Marks stated that at CBER, “we are trying to be very fair about how we prioritise things, not favouring one sponsor over another while acknowledging that certain products rise to the top and need to be looked at more quickly than others.”
He continued, “This is really about being a good portfolio manager. We need to ensure that what is urgent is taken care of while acknowledging that things that may take a little longer to get there may turn out to be very important products.”
“A vaccine that may make it first may give 50 percent protection, which we would take right now as it would give similar efficacy to the flu vaccine but would not wipe out the virus. Another potential vaccine may give 80 percent protection, so we need to keep that moving. That goes with other products as well,” Marks added
The industry has focused on trying to be successful in developing COVID therapeutics, not narrowly focusing on its own interests but taking a broad approach and considering potential combination
Both Marks and Stein were also at pains to highlight how the FDA is looking closely at repurposing existing therapeutics as the fastest way to get treatments to patients. Stein said, “Early on, ACTIV developed clear criteria for selection of drugs then got a lot of information about candidate drugs that could be repurposed and made very rational choices. The intent is to be as broad as we can in moving forward drugs that have the potential to add value.”
Utilising combination approaches is also key. “The industry has focused on trying to be successful in developing COVID therapeutics, not narrowly focusing on its own interests but taking a broad approach and considering potential combinations,” noted Stein. “Combinations are going to have to be considered early – that is part of the discussions we are having.”
While a substantial amount of the FDA’s resources have been pivoted towards COVID-19, both Marks and Stein are cognizant of the pandemic’s impact on other therapeutic areas and how different and challenging a post-COVID world may be.
“What keeps me up at night is what is going to happen in the post-COVID world,” said Marks. “One of my worries is that I see us having several vaccines that are going to need approval in the coming months. As we clear over COVID-19, I foresee this pent-up demand for cell and gene therapies, products that have had almost a stalled development because of the pandemic.”
I feel like a sailor in the middle of the North Atlantic with no land in sight. We don’t yet have the comfort of having a vaccine or a very effective therapeutic in sight
He continued, “This is in addition to salvaging what we can from Phase III trials for products where samples may not have been done or levels may not have been obtained. These are trials with small patient populations where it would be unethical to not do our absolute best to make every patient count. It ends up being a custom shop, going trial by trial and seeing what we can salvage. The post-COVID world is going to be very busy.”
On clinical trials, Stein noted that “there has been a huge impact.” He added, “We put out a guidance fairly early on to try and provide instruction and council and mitigate impact on trials. We are now working on providing guidance on impact and how to manage that impact. The FDA cannot change its substantial evidence standard but can be sensitive and flexible on how it is applied. No-one wants to see potentially very effective drugs delayed and trials having to be redone. On the other hand, if the evidence is not sufficient to demonstrate benefit, a drug cannot be approved.”
Marks finished, “I feel like a sailor in the middle of the North Atlantic with no land in sight. We don’t yet have the comfort of having a vaccine or a very effective therapeutic in sight. We are unfortunately, in a place where we can be whipped by storms very easily, some of the issues that have been going on recently show how things that might normally be managed differently can get out of control quickly.”
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