The annual J.P. Morgan Healthcare Conference in San Francisco is a January tradition at which the leading biotech and pharmaceutical companies announce their major news and discoveries. At this year's virtual meeting, leaders from the pharmaceutical and biotech industries were focused on the COVID-19 pandemic. The first day of the conference, Monday, January 11, was devoted to current development of therapeutics. The following two days were focused on vaccines, including the upcoming second-wave of vaccines and logistical management of vaccine distribution. The ASA Monitor was in attendance and now brings you a front row seat to three of the meeting's enlightening panel discussions.
January 11, 2021: “In-Development COVID-19 Therapeutics”
In this first session of the conference, the panel members explained how the therapies currently being developed fit into the overall management of patients with COVID-19. Wendy Holman, CEO and Founder, Ridgeback Biotherapeutics, noted that COVID-19 is here to stay, and although it will change over time, there will never be a one-size-fits-all approach to treatment. “It's important to have multiple shots on goal, and thus potential combination therapies,” she said. Julie Kim, President of the Plasma-Derived Therapies Business Unit, Takeda, agreed that the multiple shots on goal concept is critical given our limited understanding of the disease, particularly the long-term consequences. The importance of all companies working in this space to develop the arsenal that is necessary to combat the COVID-19 variants was emphasized.
Next, the panel turned to what we have learned from our experience with the antiviral drug remdesivir and antibodies that have received emergency use authorization to treat COVID-19. We have learned a lot from the clinical trials that have been completed. A one-size-fits-all model does not work because we cannot anticipate the course of the disease. A patient intubated in the ICU is very different from another who requires only oxygen via nasal canula. Levi Garraway, MD, PhD, Chief Medical Officer, Roche and Genentech, mentioned that another important discovery was the different stages of the disease over time. “Early on, we know that viral replication was clearly driving the pathogenesis,” which he said makes good sense to use antivirals or cocktails of neutralizing antibodies. “Later on,” Dr. Garraway continued, “the inflammatory response to the virus becomes a challenge, and that's why steroids have shown a mortality benefit.”
We have a lot to learn about how individual patient factors and comorbidities impact prognosis. For example, early on it was observed that patients with T-cell deficiencies had poor outcomes. An existing T-cell therapeutic was developed and considered for combined treatment with therapeutics therapies such as plasma or monoclonal antibodies that address the humoral response.
There may be several silver linings. The process of drug discovery itself has changed, reflecting the integration of different companies' products into streamlined protocols that have facilitated the progress of discovery. Further, the clearly enhanced risk to underserved populations has brought attention to improving service and access.
January 12, 2021: “Second-Wave COVID-19 Vaccines”
In their initial discussion, the panel tackled the question of whether more vaccine candidates were needed. Several themes echo those from the previous day's discussions. In summary:
The amazing results from the two initial vaccines will help end this acute phase of the pandemic. However, given that COVID-19 is likely to become endemic, continued vaccine development is important to plan for long-term management of the disease. More vaccines will likely be needed to cover the world population of 8 billion. Improved characteristics that will be important include vaccines that only require one dose and do not require very low temperature storage. Improving scalability has been problematic with the existing mRNA vaccines and is an important barrier to overcome. As we address these issues and questions such as the duration of protection and variability in coverage of target populations, we will need more vaccines that can overcome these limitations.
“The process of drug discovery itself has changed, reflecting the integration of different companies' products into streamlined protocols that have facilitated the progress of discovery. Further, the clearly enhanced risk to underserved populations has brought attention to improving service and access.”
Panelists discussed specific must-haves for second-wave vaccines. Countries will have different national vaccine strategies, however, storage in a traditional refrigerator between 2°C and 8°C is key. Much of the world does not have continuous reliable access to colder facilities. A vaccine that only requires one dose will obviate the problems of assuring return for the second dose and questions about whether you can mix and match the different vaccines. A single dose requirement will also limit the secondary cost of goods such as syringes and vials. Future knowledge of the changing pathophysiology of the disease and pharmacology of the different treatments will provide information about other features that will need to be addressed.
Next, the panel members provided exciting news about expectations for their individual vaccine programs over the next six to 12 months.
Swati Gupta, DrPH, MPH, Vice President and Head of Emerging Infectious Diseases and Scientific Strategy, IAVI, noted, “We're working on a recombinant vesicular stomatitis virus (rVSV) vaccine, which is based on a weakened animal virus that doesn't cause disease in humans; we insert a piece of genetic code for SARS-CoV-2 for the outer surface protein and take out the genetic sequence for the VSV surface protein, which then makes the virus a vector.” They envision this to be a single-dose vaccine that will work rapidly. They are also looking at vaccine preparations that can work orally or intranasally. This program is in collaboration with Merck, is currently in Phase 1 with patient enrollment having begun in November 2020.
According to their website, Medicago uses a plant-based platform to develop their vaccines. They use plants to create non-infections versions of their vaccines. Nathalie Landry, Executive Vice President, Scientific and Medical Affairs, Medicago, said that they are only a few weeks away from announcing their Phase 2 results and launching their Phase 3 study. “We are quietly hopeful that the safety and efficacy data will be obtained by the summer when we will be applying for the authorization of the vaccine in different countries,” she said. “And, finally, we are discussing a pediatric plan with the regulators where we want to evaluate immunogenicity in pediatric, as well as in pregnant populations.” They also plan to evaluate the duration of protection, cross-protection, and cross-reactivity, to address the new mutants.
Thomas Lingelbach, President and CEO, Valneva, explained that they are currently conducting a combined Phase 1/2 trial collaborating with the National Institute for Health Research in the U.K. They expect to have data from the trial by March. At the same time, they are preparing for a Phase 2/3 immunogenicity study in addition to trials targeting special target populations.
January 13, 2021: “The Last Mile: How Will a COVID-19 Vaccine Make It From Plant to Patients?”
The timeline for vaccine administration to the general public is limited by inventory available from the manufacturers for the U.S. who must still honor their global commitments. It isn't possible for the CDC to declare a “magical” phase 2 and general population availability. Currently, the Advisory Committee on Immunization Practices recommends prioritization of seniors and frontline essential workers. The next phase, 1C, will be other essential workers and adults with comorbidities. Together, that is about one-half to two-thirds of the U.S. population. The general population phase is really about people who aren't necessarily at high risk for some other reason.
A separate but related question is how and when the vaccine can be distributed across a network of more than 10,000 pharmacies via appointments made online. It is important to divert pressure on physician's offices to protect patient care by providing services at pharmacies that traditionally provide vaccines. The U.S. Department of Health and Human Services has announced two federal pharmacy partnerships; first was CVS and Walgreen's under long-term care, and the second was a broader set of chain pharmacies who would have broader access to a direct federal allocation of supply. Adding federal supply to pharmacies to state allocations will speed things up. It also greatly increases the sites of administration. Heather Zenk, RPh, PharmD, SVP of Strategic Global Sourcing, AmerisourceBergen, noted, “I've always thought of this as a two-lane highway: you've got the state allocation and then you've got the more traditional federal, in which normal Americans go in and get the Shingrix vaccine and maybe get a flu vaccine every year and then maybe get their pneumovax and with all of those, it just becomes commonplace and the COVID vaccine gets rolled into that.”
The panel then addressed how the vaccination efforts for COVID-19 would differ from those efforts for the H1N1 influenza. J. Stephen Jones, MD, President and CEO, Inova Health System, noted that one of the biggest differences between COVID-19 and H1N1 vaccination is the COVID-19 requirement for 15 minutes of observation after vaccination. “To my knowledge, we don't require that for any of our other vaccinations, at least the ones that I am directly involved in,” he said, adding that asking that many people to sit somewhere for 15 minutes creates a giant complexity in this mass vaccination effort.
“It is important to divert pressure on physician's offices to protect patient care by providing services at pharmacies that traditionally provide vaccines.”
Unprecedented change, lessons, and accomplishments
In conclusion, the consensus from this conference was that the old ways of doing things cannot be applied to management of SARS-CoV-2. The first two vaccines authorized for use in the U.S. from Moderna and Pfizer/BioNTech are unique mRNA vaccines, a model that has never previously been approved for large-scale administration. The rapidity with which these vaccines have undergone development is completely unprecedented and has taxed both developers and regulatory agencies alike. However, novel solutions and procedures have been put into place that may forever change the way vaccine or pharmaceutical development is done in this country and worldwide. New development will be required but the good news is that there are multiple shots on goal.