Independent of the current pandemic, life sciences companies frequently reevaluate their product pipeline programs on a variety of dynamic clinical and commercial factors. With COVID-19 reshaping healthcare and introducing widespread clinical trial delays, the calculus for pipeline prioritization has changed. When reprioritizing programs now, we believe that pharma companies should focus on trials for life-threatening conditions, protect patient safety and limit the use of hospital resources.
Beyond these factors, however, there is potential to adapt drug development in a COVID-19 world. There are strategies that biopharma can employ to continue safe innovation during this global pandemic. Some clinical trials should stay the course while others may need to pause. Some, however, might be able to proceed through use of one or more mitigation strategies.
Re-prioritizing the pipeline
To the extent possible, companies may aim to preserve the continuity of their clinical trials. Patients can maintain their course of therapy without the potentially negative consequences of treatment disruption. In addition to individual patient value, study continuity protects the integrity of data generated by clinical trials, which can take years of effort and dedication to produce and contributes significant value to society. As such, fully-enrolled late-stage trials will likely take priority over early studies that are still recruiting. When accounting for COVID-19, pharma companies should observe three additional guidelines:
- Ensure that life-or-death treatments are available. First and foremost, clinical trials where enrollment could represent the difference between life and death for a patient should remain prioritized as much as possible. Prioritized trials could include programs for severe oncological diseases with few available options, such as glioblastoma, pancreatic cancer and late-stage lung cancer, as well as some rare diseases. We have seen cancer patients continue their hospital visits during the crisis due to medical need; UCSD cites little disruption to cancer trials to date, despite their non-cancer study visits decreasing by over half. Pfizer has continued some oncology and gene therapy trials for this reason, despite pausing other pipeline programs. If a sponsor does proceed with a clinical program, they must be ready to ensure that trial sites agree that the trial’s benefits outweigh both COVID-19 infection risks and the use of hospital resources.
- Protect patient safety. Companies should evaluate how reliant their trial’s enrollment is on patients with elevated risk of complications from COVID-19. This could include patients who are immunocompromised, have risk factor co-morbidities and those who are 65 or older. We’ve recently seen Galapagos, Provention and Addex Therapeutics each stop or delay their trials to protect such vulnerable patients.
- Reduce the burden on healthcare systems. Pharma companies may consider the extent to which a program might compete for resources needed to treat COVID-19. Respiratory and infectious disease programs, for example, have good reason to halt enrollment in order to avoid pulling infectious disease specialists and pulmonologists from the front lines of COVID-19.
However, it’s not just physician time that’s a precious resource. Hospital beds and equipment are in short supply as well. Clinical programs that require extensive hospital time and engagement should also be considered potentially burdensome. For example, some cell and gene therapy trials often require repeat hospital visits to collect cells and administer treatment, and to undergo extensive in-patient monitoring. Such trials may be worth reevaluating. BMS has suspended screening, enrollment and apheresis for all cell therapy clinical trials. AVROBIO is continuing to screen patients for its early stage gene therapy trials but will not treat patients until sites are ready to resume elective procedures. On the other hand, investigational therapies that provide an alternative to surgery or other hospital resource use may stay the course. Urogen’s UGN-101 may be the first non-surgical option for LG UTUC and its administration may free up hospital resources that could be redirected to COVID-19.
Adapting drug development in a COVID-19 world
Despite these challenges, there may be opportunity to redesign clinical programs to face less impact from COVID-19. When prioritizing trials, companies should consider their ability to adjust using the following strategies:
- Shift trial site locations. Companies can continue to move programs forward by recruiting in geographies expected to be less impacted by COVID-19 in the future or that have passed their likely peak of infection. Globally, this could include locations where the impact has been less severe, like Germany or South Korea. It may also include selecting sites outside of the most affected U.S. regions to the extent possible. Recently, Pfizer and Merck have signaled that they would continue trials in Asia while suspending enrollment in other regions due to the virus. Of course, the pandemic is dynamic so trial operations must be responsive and flexible enough to adapt to the virus’s changing footprint. Astellas has modified its clinical trial operations to suspend new studies in countries with rapid COVID-19 growth and resume trials in areas no longer experiencing such growth.
- Consider remote trials. Clinical teams should assess the extent to which they can conduct trials remotely. Studies with patient-reported outcomes as primary measurements, for example, or those with less frequent timepoints and data collection, such as studies for chronic diseases, may be able to transition to site-less trials or employ telemedicine. Vertex has altered its approach and is working with trial sites to enable virtual clinic visits and home treatment delivery. Remote trials may be less feasible when they require in-person evaluations such as imaging or antibody testing. However, Reata, has adjusted its phase III trial of bardoxolone for chronic kidney disease from Alport syndrome to include at-home visits to collect blood samples and assess safety.
- Create adaptive protocols. Adaptive designs may increasingly make trials more efficient and safeguard against COVID-19 risks, allowing for pre-planned trial modifications in response to early results. This may include shifting focus to only those patients most likely to benefit from treatment, as well as planning around COVID-19 high-risk groups. For example, a trial could enroll patients over 65 only after an initial efficacy or safety signal has been established and peak infection has passed.
- Leverage real-word data. Even before the pandemic, trial sponsors were increasingly embracing real-world or historical data as synthetic control arms to accelerate drug development, limit costs and overcome recruitment challenges. Now, this may represent a feasible alternative to limit healthcare system burden. Programs for diseases with extensive data availability, like those with substantial patient populations or long-established disease coding, may have the greatest opportunity to adopt real-world data. The FDA has recently issued multiple approvals based on external control arms, signaling the regulatory risk may be limited for pipeline programs exploring this option.
- Identify COVID-19 development opportunities. Manufacturers should consider the potential of their pipeline assets to address COVID-19. We have begun to see numerous manufacturers pivot assets initially investigated for other conditions toward prevention and treatment of the virus and its complications. For example, Genentech and Sanofi/Regeneron have announced recent COVID-19 trials for IL-6 inhibitors that target lung inflammation (Actemra and Kevzara, both approved for rheumatoid arthritis and being explored for other immunology conditions). Similarly, Incyte and Novartis will test their JAK1/2 inhibitor, Jakafi, in a Phase 3 trial for patients with cytokine storm, an immune overreaction seen in some COVID-19 cases. AlloVir is also expanding its investigational T-cell therapy ALVR106 to include COVID-19 patients.
Whether a program is suspended for patient safety concerns or altered to better suit the healthcare environment, manufacturers should look to FDA guidance that covers trial pauses or protocol adaptation. All protocol changes should be reviewed by institutional boards and independent ethics committees. Pipeline planning should also account for the possibility of missing data or skipped visits by patients in statistical analysis and documentation.
COVID-19 is forcing pharmaceutical companies to rethink their opportunities ahead. Each day we are seeing more manufacturers answer difficult questions about how to proceed with their pipeline. Manufacturers have an opportunity to explore ways to minimize in-person, site-of-care visits through reexamining their digital and real-world data capabilities and add flexibility to their clinical trial operations. After the pandemic, these approaches may continue to be useful lenses through which to think about pipeline decision-making.