Prothena is committed to developing novel and transformative medicines to create a better future for patients with neurodegenerative and rare peripheral amyloid diseases, which affect millions of people and their families worldwide. Before any treatment is made available to patients in the U.S., it must go through a rigorous set of clinical and nonclinical testing and receive approval from regulatory agencies, such as the U.S. FDA. This regulatory body is a critical part of the process of getting medicines from our labs to the patients who need them most. We recently spoke with Carol Karp, Chief Regulatory Officer at Prothena, to hear about how Prothena’s regulatory team helps navigate the regulatory process and how things have evolved over the course of her career. Check out her perspective below.

Q: What drew you to a career in regulatory affairs?
A: I started out working in labs, first in basic and later in applied research, where I was introduced to regulatory affairs through a pharma course. I was drawn to regulatory for several reasons. First, its overarching strategic focus, together with the need to overcome challenges and hurdles drew me in, as did the ability to help guide the development of products from the laboratory to the clinic and ultimately to patients. Working on products through their entire life cycle was also very appealing to me, as was the opportunity to collaborate across a broad cross section of different functional areas in an organization, from nonclinical and clinical, biostatistics, commercial and many others. Finally, integrating strategies and information to advance product development through negotiations with regulatory authorities was very intriguing, and still is.

Q: How has the regulatory landscape changed over the course of your career?
A: The landscape has changed dramatically, from an industry focused on small molecules and large patient populations to one that encompasses monoclonal antibodies, gene and cell therapy, and more personalized medicines. On top of that, regulatory science has evolved to encourage and better enable the development of therapies for orphan and pediatric diseases. Alzheimer’s disease is a great example of how the landscape has changed, with major scientific and medical advances enabling the development of disease modifying therapies through the use of biomarkers that can both enrich clinical trials and redefine endpoints in support of regulatory approval.

Q: What led you to Prothena?
A: While at a previous company, I had an opportunity to collaborate with members of the Elan team, including Gene and Wagner on the development of a monoclonal antibody as well as a vaccine for Alzheimer’s disease. Later, in 2016, we crossed paths again on work related to initiation of the VITAL trial for birtamimab*. I was very impressed by Gene’s leadership approach, the entire organization’s steadfast focus on both the science and patients, the Prothena pipeline, and the highly collaborative approach of the team. After joining Prothena as a consultant in 2016 as acting Head of Regulatory Affairs, I officially joined the organization in December of that year. That same commitment to the science, unwavering patient focus, leadership and collaboration are why I have stayed for all these years.

Q: Tell us what the regulatory team is responsible for at Prothena.
A: The regulatory team is primarily responsible for developing regulatory strategies and leading regulatory interactions, particularly with the FDA, EMA and PMDA, to expedite the development of our products. The team includes Regulatory CMC, focused on the strategy for submissions and interactions related to the chemistry, manufacturing and controls for our products; Regulatory Operations, focused on publishing of all of our regulatory documents and submissions through Veeva; Global Regulatory Portfolio Management, responsible for managing timelines and planning for regulatory submissions and interactions; Medical Writing, focused on documents such as clinical protocols, IBs, CSRs, briefing documents and more; and Regulatory Strategy, focused on just that for FDA and for EMA and other regulatory authorities. The work of the entire team is aimed at advancing our investigational products into the clinic at the IND stage and toward registration and patients at the BLA stage.

Q: How does the regulatory team at Prothena inspire you?
A: I am very fortunate to have such a great team to partner with. They are truly resolute in their dedication and commitment to achieving our goals and milestones, collaborating across the organization to streamline and optimize processes and timelines to help advance our portfolio. The team, like all Prothenians, is very patient-centric, and mindful of our core values, including being joyful while under pressure. I am inspired by the can-do attitude of the regulatory team, with their focus on doing what is best for both the overall organization and for patients, with the work we all do having the potential to positively impact the lives of thousands of patients with AL amyloidosis and millions of patients with Alzheimer’s disease.

Q: What are you most proud of the Prothena regulatory team for accomplishing?
A: The birtamimab* special protocol assessment (SPA) agreement with the FDA tops the list, at least for now. Based on a post hoc analysis of the VITAL clinical trial data, which showed a significant survival benefit in Mayo Stage IV patients treated with birtamimab*, we went back to the FDA and successfully negotiated an agreement for the Phase 3 AFFIRM-AL confirmatory trial in Mayo Stage IV patients, with a significance level of 0.1 for the primary endpoint of time to all-cause mortality.

More recently, the regulatory team successfully completed two IND filings less than one month apart for PRX123*, our first IND in CBER, submitted one month early, and for PRX019*, submitted six months ahead of schedule, a truly heroic effort. We also received Fast Track designation for PRX123, a testament to our science, teamwork and collaboration.

*Birtamimab is an investigational therapy for the potential treatment of Mayo Stage IV AL amyloidosis; PRX019 is an investigational therapy for the potential treatment of neurodegenerative diseases; PRX123 is an investigational therapy for the potential treatment of Alzheimer’s disease