Boosting Drug Development

BioPharm International, BioPharm International-02-01-2021, Volume 34, Issue 2
Pages: 12–14

New approaches to clinical trials, spurred by the COVID-19 pandemic, have dramatically shortened development timeframes. Can these gains be sustained once conditions return to normal?

Despite the limitations set by the COVID-19 pandemic, bio/pharmaceutical manufacturers achieved unprecedented speed in developing new products in 2020. This was evident with the first two COVID-19 vaccines, which reached the public under Emergency Use Authorization in December 2020. Where developing a vaccine has traditionally required 10 years, Pfizer-BioNTech and Moderna Therapeutics cut that time to less than a year (1,2) with their messenger RNA (mRNA) vaccines.

Developers attribute this speed to developers’ willingness to assume more risk from the start and to leverage years of past research and clinical experience with the platforms themselves (e.g., mRNA or, in the case of Johnson & Johnson’s (J&J’s) COVID-19 vaccine candidate, with human adenoviral vector [Ad26]). With J&J’s vaccine, cell-line optimization was also crucial, not only for speeding the vaccine’s development but for optimizing its manufacturability and stability, as Paul Stoffels, executive vice president and chief scientific officer told attendees at the 2020 Galien Forum (3). Stability was optimized to levels of 2-8 °C, simplifying global distribution to developing nations.

However, with COVID-19 vaccines and therapies, the greatest increases in developmental speed and agility were achieved on the clinical side. New adaptive clinical study models were used; some early testing in humans was done concurrently with animal testing; some safety tests were run simultaneously with efficacy tests, and elements of Phase II and Phase III trials were combined.

Even on the preclinical side, work on Moderna’s COVID-19 vaccine was accomplished within a few months, CEO Stéphane Bancel explained at the 2020 Galien Foundation Forum (3). Scientists had sketched the experimental design in January 2020; the first test product was sent to the US National Institutes of Health in February; and Phase I testing started in early March. By the autumn of 2020, chemistry, manufacturing, and control (CMC) documentation had been submitted to FDA while safety testing was still going on.

Clearly, achievements in time reduction for COVID-19 therapies and vaccines have proven what is possible and set the bar high. One question is whether achievements made during a time of crisis can be sustained after the pandemic and move into mainstream bio/pharmaceutical development. New approaches, and the use of innovative technology, promises to enable additional gains in speed and efficiency.

A number of trends have already been in place to speed new drug development, including increased use of biomarkers and better patient targeting during clinical stage planning. In addition, more bio/pharma companies are using data analytics. One platform that is seeing increased adoption is artificial intelligence/machine learning (AIML), which can be applied to real-world data, including such diverse data sources as electronic health records, lab test results, and insurance claims, to ensure that trial design and patient recruitment reflect actual conditions.

Efforts by FDA and other regulatory agencies to speed review of important new drugs have also helped shrink development timeframes. Where the first decade of the 2000s saw slower development times and higher attrition rates for new drug candidates, notable increases in efficiency were made between 2010 and 2020, according to a recent study (4).

In a speech on June 1, 2020 (5), former FDA Commissioner Stephen Hahn pledged to make permanent some innovations that the industry and agency made to increase agility during the pandemic. He emphasized FDA’s interest in advancing practices such as decentralized clinical trials and increased use of real-world evidence in clinical trials. Technology is becoming increasingly important in optimizing study design, site selection, and patient recruitment, and also in predicting R&D and clinical outcomes, to help prioritize, early on, the most promising candidates, says Natalia Kotchie, vice president of R&DS Applied Data Science Center at the contract research organization, IQVIA.

Moderna used predictive models in the earliest phases of its COVID-19 vaccine development planning (3). As a CRO, IQVIA has been developing AIML-based tools and systems for the past five years to optimize clinical trials, for example prioritizing the highest potential sites. During the pandemic, IQVIA-developed COVID-19 models informed trial operational planning choices depending on areas where COVID-19 outbreaks were most likely to occur, says Kotchie.

More collaboration

For bio/pharma companies, one fundamental change that is speeding drug development has been increased collaboration and cross-learning through partnerships, says Lance Minor, national co-leader of life sciences practice for the management consultant, BDO USA LLP. The industry has engaged in collaborative research for decades, but during the current pandemic, the level of collaboration intensified, bringing together competitors such as Roche and Regeneron, Gilead and Roche, Gilead and Pfizer, Sanofi and GlaxoSmithKline (GSK), as well as companies working in incubators set up by the World Health Organization, the Global Alliance for Vaccines and Immunizations, the Coalition for Epidemic Preparedness Innovation, and the Gates Foundation (6).

Close work involving bio/pharma companies, CROs, and healthcare organizations has added another dimension to collaboration, Kotchie says. Another important factor speeding development of COVID-19 treatments and vaccines has been drug developers’ increased tolerance for risk, not only on the capital and financial side, but in the clinic, Minor says. Pfizer-BioNTech and Moderna spent billions of dollars on development for COVID-19 vaccines, but they also took risks by changing the traditional sequential approach to clinical testing, Minor says. In 2020 assuming these risks, and managing them, paid off in shortened development times. In 2021, novel approaches to enrolling patients and use of remote patient monitoring should also have an impact, he says.

Although efforts in 2020 focused on therapies and vaccines for COVID-19, the pace of development projects outside that area will pick up again in 2021, says Minor. Success in a very challenging year has led to optimism for 2021. In BDO’s 2021 survey, 100 chief financial officers (CFOs) at medium-to-large life sciences companies, the company found that 69% plan to increase spending on R&D, most of them singling out three or four promising products as commercialization targets. Pharma companies are still planning to increase investment in the development of new COVID-19 treatments, but a larger number also plan to invest in other therapeutic areas, with 57% mentioning cell therapies (up from 41% in 2020) and 56% targeting immunotherapies (up from 32% in 2020) (7).

Significantly, many respondents to the 2021 survey see digitalization as important to achieving their goals, with 63% responding that digital transformation would be their leading growth strategy in 2021.

Innovative tools

One innovation that has helped shorten drug development timeframes has been use of biomarkers, indicators of a patient’s medical state that can be readily measured that have become a mainstay for clinical trials. Biomarkers were used in 55% of oncology clinical trials alone in 2018, up from 15% 20 years ago (8). FDA has recognized biomarkers’ importance since the agency first established its Critical Path initiative in 2004. More recently, however, FDA has begun to recognize other innovative drug development tools that are expected to help shorten drug development times, a mandate of FDA’s 21st Century Cures Act. On Nov. 30, 2020, FDA established a new pilot program, the Innovative Science and Technology Approaches for New Drugs (ISTAND) (9).

The effort could break through some of the industry’s reluctance to use technologies that have not first been applied in approved new drug applications. Through ISTAND, technology developers can apply to FDA for qualification of a novel technology for a specific use. The pilot would cover new, nontraditional data collection or analysis methods; technologies such as tissue chips that serve as micromodels of specific organ systems for drug safety assessments; and use of artificial intelligence and wearable sensors, which could be used during clinical trials.

To strengthen its foundation for data analytics, FDA has been working on initiatives in food import screening and medical devices. For pharma, key targets are drug safety testing and development of real-world data approaches.

In December 2020, FDA signed contracts with Palantir and SAS to build the database foundation required (10,11). Bio/pharma companies, including Novartis, Roche, Merck, Pfizer, AstraZeneca, and GSK, have also been actively working in this area, with more firms using AI for clinical trial optimization (12).

Among the challenges for pharma companies that have already embraced new technology is finding, cleaning, and reorganizing data to be research-ready so that AIML platforms can yield useful results, says Kotchie. Another new capability that will be required, she says, is the ability to translate business problems to how users make decisions, and ensure that the user experience of new systems is able to maximize the application of the models developed. “This is an area that the new discipline of ‘decision intelligence’ is helping us to address,” Kotchie says.

Clinical trial advances

But even without the advantage of new technology, clinical trial flexibility has had to be balanced by strict risk evaluation and management. Business continuity programs have been crucial, says Teresa Lamentia, senior vice-president of operational transformation and performance at IQVIA, who also leads the company’s COVID-19 task force for R&D.

IQVIA’s clients range from small innovators to large pharma companies, and although some firms had to halt projects in 2020, most have restarted efforts, she says. “We’re not back to previous levels, but recruitment is definitely increasing and this trend should continue in 2021,” she says.

Lamentia and her team take a three-pronged approach, examining every trial protocol from the standpoints of patient safety, data integrity and robustness, and day-to-day realities affecting site visits (e.g., to ensure that subjects receive trial drugs and have necessary tests performed when COVID restrictions cause a site to be shut down).

Detailed reports were then developed to ensure that risks would not affect pharma clients or patients. As she notes, the company had to adopt remote approaches, for dosing or for patient testing, and wound up taking a hybrid approach combining on-site and remote elements.

This method demanded that both the CRO and pharma company pay close attention to supply chain issues. For IQVIA, an especially challenging problem was the sourcing of personal protective equipment and ancillary products for technical and business staff. Outside the United States, particularly in the United Kingdom and European Union, conformance with patient data protection regulations was another challenge.

In general, clinical trials are being run to optimize flexibility. “Taking an ‘umbrella’ approach to protocols allowed us to be able to perform more tests concurrently,” Lamentia notes.

It is not yet clear which new methods adopted during the pandemic’s first year will become permanent best practices, she says, but she expects to see more remote study approaches and more flexible clinical trial designs dominating drug development in the future. Based on regulatory and corporate plans, data monitoring and analytics promise to play an increasingly important role as well.

REFERENCES

1. J. Hopkins, “How Pfizer Delivered a COVID Vaccine in Record Time,” The WallStreetJournal.com, Dec. 11, 2020.
2. S. Mukherjee, moderator, “Can a Vaccine for COVID-19 Be Developed in Pandemic Time”, New York Times Magazine, June 9, 2020.
3. A. Shanley, “The Last Mile: COVID-19 Vaccine Developers Prepare to File for Emergency Use Applications,” PharmTech.com, Nov. 11, 2021.
4. F. Pammoli et al, J. Translational Medicine 18 (162) (2020).
5. S. Hahn, “Remarks by Commissioner Stephen Hahn MD on the COVID-19 Pandemic—Finding Solutions and Applying Lessons Learned,” fda.gov, June 1, 2020.
6. C. Leaf, “The Whole World is Coming Together: How the Race for a COVID Vaccine is Revolutionizing Big Pharma,” Fortune.com, Sept. 21, 2020.
7. BDO Life Sciences, “2021 BDO Life Sciences CFO Survey,” Report, January 2021.
8. A. Vadas, T.J. Bilodeaux, C. Oza, “Special Report: The Evolution of Biomarker Use in Clinical Trials of Cancer Therapies,” journalofprecisionmedicine.com, 2019.
9. FDA, “Innovative Science and Technology Approaches for New Drugs (I-Stand)” fda.gov, Nov. 30, 2020.
10. C. O’Donnell, “Palantir Wins $44 million FDA Contract,” Reuters.com, Dec. 7, 2020.
11. SAS, “FDA Inks $49.9-Million Dollar Deal with SAS”, sas.com, Jan. 11, 2020.
12. Novartis, “AI at Novartis,” Novartis.com, accessed Jan. 14,2020.

Article details

BioPharm International
Vol. 34, No. 2
February 2021
Pages: 12-14

Citation

When referring to this article, please cite it as: A. Shanley, "Boosting Drug Development." BioPharm International 34 (2) 2021.