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Biosimilars & Gene Therapy Development Open ISPE’s 1st Virtual Conference

Susan Sandler
Biosimilars & Gene Therapy Development Open ISPE’s 1st Virtual Conference

2020 ISPE Biopharmaceutical Manufacturing Virtual Conference

ISPE’s first virtual conference, the 2020 ISPE Biopharmaceutical Manufacturing Virtual Conference, is a new format for delivering education, information, and networking—a fitting first virtual meeting for ISPE given the cutting edge nature of the subject matter of biopharma, cell and gene therapies, and ATMPs. Like these technologies, ISPE and the conference attendees are adapting to new modalities—driven by the impacts of the COVID-19 pandemic—to embrace a new way of meeting and exchanging information.

Virtual Conference Debut

Tim Howard, interim President and CEO of ISPE, noted that over 20 countries were represented by the conference’s attendees. Originally planned for Boston, the meeting was changed to a virtual meeting because of the COVID-19 pandemic. Howard recognized the long hours of hard work invested by ISPE staff to make the change a reality, and also thanked the Biopharma conference planning committee for embracing the change needed and their partnership with ISPE staff. Howard noted that conferences are as important as ever for the industry to be able to continue its work on treatments and vaccines.

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Tom Hartman, ISPE’s incoming CEO and President, welcomed attendees by noting the tremendous progress that has been made in the biotech industry over the previous four decades. Biotechnology has had a significant impact on the healthcare industry, and he predicted continued growth. Hartman noted that ISPE is central to providing opportunities such as the Biopharma conference and the 2020 ISPE Continuous Manufacturing Virtual Workshop on 3—4 June to advance the latest industry thinking and share ideas that can be leveraged by all participants to solve problems.

Conference Overview

Joseph C. Famulare
Vice President, Global Quality Compliance and External Relations
Genentech, A Member of the Roche Group

Joseph Famulare, Conference Chair and Vice President, Global Compliance and External Collaboration, Genentech, gave an overview of the conference and the opening presentations. He noted that what brings the industry and attendees together—no matter what the location–is the desire to deliver more to patients, the obligation to deliver quality products faster, and the need to fully integrate technology now and as a pathway to future.

Eric D. Felz
Associate Director Validation
Takeda Pharmaceutical Company Limited

Eric Felz, president of the ISPE Boston chapter and a member of the conference committee, welcomed attendees on behalf of the 1,500-member Boston chapter that was the original host chapter. Felz said was honored to attend ISPE’s first virtual conference.

Biosimilars Growth

Carol Lynch
President, Sandoz US, Head, North America
Head, North America
Sandoz US Inc.

Carol Lynch, President US, Sandoz, gave the first presentation during the opening plenary, “Reflecting on a Decade with the Biologics Price Competition and Innovation Act (BPCIA).” The BPCIA was enacted as part of the Affordable Care Act, and her commentary looked at its impact to date as well as looking ahead to the future of biosimilars in the US.

The BPCIA provided a regulatory pathway for abbreviated licensing of a biological treatment; created incentive for manufacturers to develop more affordable biologic treatments for the US market; and enabled manufacturers to confidently design and manufacture a biological drug that closely matches the complex structure and function of the reference through biotechnology advancements, she noted.

More companies are now making biosimilars, which potentially improves patient access and generates savings for health systems, Lynch said. Since 2015, 26 biosimilars have been approved in the US by the FDA. Her company, Sandoz, was the first to get approval for Zarzio. The US was late to join in biosimilars, but now “we are making up time,” she said: ten approvals were received in 2019, and seven in 2018. Not all approved products have been launched or commercialized yet among the 26 approved, she noted; only 16 have taken those steps.

Biologics have had a profound effect on patients, she noted, and may bring significant healthcare savings. More affordable medicines increase access to medicines by patients and this has been seen in other areas of the world, she said. Lynch estimated approximately $54 billion of savings in the US could be realized with reasonable adoption of biosimilars in the marketplace.

These savings benefit a range of stakeholders in the health market from employers through the patients themselves. Patient access improvements include eligibility for treatment, earlier start to treatment, and improved outcomes due to earlier start to treatment. Patient care benefits for facilities like hospitals include more patient support from staff, access to biologics, shorter waiting times, and simplified administration procedures. Good adoption of biosimilars is needed to be able to reap these benefits. “Availability is the start but not the end of the story.”

Sandoz has seen the changes in biosimilars in the US spanning from its approval in 2015 for Zarzio to its most recent approval, Ziextenzo. Although there have been changes, challenges still remain for biosimilars in the US, Lynch said. There is still confusion about what biosimilars are, Lynch noted. While regulatory challenges have come a long way, she observed that interchangeability can create the perception of a two-tier system with biosimilars being different. This can lead to potential confusion. Other challenges include rebates for pharmacy benefit providers and positive payment incentives for driving large-scale adoption.

Another challenge is looming because of the challenge to the constitutionality of the Affordable Care Act pending before the US Supreme Court. Should the ACA be found to be unconstitutional, then the BPCIA potentially could be eliminated, leaving no path for approvals of biosimilars in the US.

Despite challenges, Lynch said the future for biosimilars is a strong one since it can help struggling health systems and offer potential savings to those systems. For patients, biosimilars can bring greater access. “Until all patients who need [the drugs] can get access, our work is not done.”

Gene Therapy

Wilson W. Bryan, M.D.
Director, Office of Tissues and Advanced Therapies

Wilson Bryan, MD, Director, Office of Tissues and Advanced Therapies (OTAT), Center for Biologics Evaluation and Research (CBER), FDA, presented on “Gene Therapy: Efficient Drug Development.”

Bryan noted the rapid advance of gene therapy science, including more complex and sophisticated products. Alongside this has been a great increase in applications to OTAT and CBER for gene therapies. These have grown from just 44 investigational new drug applicants (INDs) in 2010, to 79 in 2016 and 245 in 2019—triple the applications in just three years.

Four gene therapies have been approved in US by the FDA so far: Kymriah, Yescarta, Luxturna, and Zolgensma. The first two are chimeric antigen receptors developed initially for cancer treatment, while Luxturna is a first-in-class gene therapy for treatment of RPE65 mutation-associated retinal dystrophy. Zolgensma is for treatment of spinal muscular atrophy type 1, which has onset in infants and generally causes death by age 2.

Zolgensma is an example of the dramatic impact of these therapies, Bryan said. In Phase 3 clinical trial, survival at 14 months of age in those treated with the drug was 67%, while the natural history controls showed 25% survival at that age. The ability to sit for approximately 30 seconds in those treated with the drug was 47%; none of the natural history control group were able to do so. He noted that natural history controls were sufficient without need for concurrent control; Bryan said the FDA is very open to considering this in some situations, adding that good natural history controls are important.

Bryan emphasized that products to treat rare diseases may be able to obtain FDA approval based on studies in a smaller number of patients. He added that new endpoints may be needed for these studies. In considering the drug development process for gene therapies, Bryan used baseball to illustrate changing ways to consider development compared with the traditional path of drug development. He encouraged sponsors and manufacturers to start thinking about “hitting home runs”—moving through all three bases or phases of clinical trial--rather than “stopping” at each base or phase as in traditional drug development. Gene therapies offer this opportunity for home runs, he said, due to scientific advances. Phase 1 studies that are designed to gather evidence of safety and effectiveness can also serve as the Phase 3 study, which is akin to the home run of baseball. Doing this successfully needs specific steps, he said:

  1. Preparation: including early collaboration between scientists and clinicians. When preclinical studies begin, draft the design of the clinical studies. This allows you to consider factors such as what natural history studies will be needed. Designing and conducting natural history studies that will support supplement drug development is part of this preparation.
  2. Play as a team: including collaboration of scientists, academic investigators, sponsors, funding organizations, patients, patient advocacy groups, and regulatory agencies. Early communication is key, he said.
  3. Try to hit a home run: design the first-in-human clinical trial to provide evidence of effectiveness like randomized controls; resolve manufacturing issues as much as possible before first-in-human clinical trial (plan on that first trial being sufficient).

Unfortunately in gene therapy, the FDA is seeing products with clinical evidence of effectiveness, but because of manufacturing issues may be another year or more before manufacturing is in line, Bryan said. More attention to manufacturing early on, and with a mindset that the first trial might suffice, can help this.

“The science has advanced for gene therapy: we can have products that change lives and save lives,” Bryan concluded. In some cases, the first-in-human study can be sufficient. He encouraged the industry to have a rigorous Phase 1 “and try for a home run!”

More ISPE Virtual Conferences are Coming!

Check out the complete list of upcoming ISPE virtual conferences and virtual training courses.


This is an abridged, unofficial summary of an FDA regulator’s presentation at a conference that has not been vetted by the agency. This article contains an informal and brief synopsis of the regulator’s presentation, and do not represent official guidance or policy of the FDA.