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Applied Clinical Trials May 2023

Ukraine invasion tests the resiliency and quick action of CROs and sponsors

Mobilizing and Maintaining Clinical Trials in Midst of War

ACT's biennial Salary Survey takes a look at the future of industry following increased adaptation of decentralized technology 

Salary Survey: The Age of COVID

Catalent has expanded the services and capabilities at its facility in Shiga, Japan, to include the storage, kitting, and distribution of advanced therapies, such as cell and gene therapies (CGTs), and at ultra-low temperatures for clinical trials.

State-of-the-art cryogenic freezers alongside material transfer equipment have been installed that are designed to retain the integrity of investigational advanced therapy products by minimizing their time-out-of-environment.

 The expansion forms part of Catalent’s ongoing global strategy to increase its ability to handle, store, and manage advanced therapies for clinical supply, and follows investments at its facilities in Philadelphia, Singapore, and Shanghai, China, in specialized, ultra-low temperature storage capabilities. The 6,000-square-meter Shiga site opened in October 2021 to support customers both locally and globally, providing flexible clinical supply solutions, including primary packaging, and demand-led supply, handling, and logistics.

Catalent Adds New Cryogenic Capabilities at Shiga, Japan, Facility to Support Clinical Supply Demand for Cell and Gene Therapy Development. SOMERSET, N.J. – May 25, 2023.

Articles

Facility upgrade will support clinical supply demand for CGT development. 

Catalent Adds Cryogenic Capabilities in Shiga, Japan

Jill Wechsler is ACT's Washington Correspondent

Recent challenges to certain controversial approval decisions has prompted FDA officials to reexamine of the role and composition of the agency’s many advisory committees and to explore options for change. With more than 50 panels composed of academics, scientists, and various interested parties, the program has become overly complex and sometimes contentious, with some up-or-down votes on important approval decisions appearing at odds with ultimate decisions by agency reviewers.

Commissioner Robert Califf has been calling for changes to improve the operations and composition of its advisory panels for several months. In a keynote speech on May 17, at the annual meeting of the Food and Drug Law Institute (FDLI) in Washington, DC, Califf emphasized the need for the agency to strengthen committee structure and methods to be “more efficient, flexible, and effective in the exercise of our regulatory responsibilities.”

 He noted the value of interchange among FDA experts and those outside the agency, particularly on complex scientific issues, and that transparent discussion is important. But he also said that the advisory committee system “can be improved” to enable FDA scientists to “get the best advice possible.”

Similarly, Patrizia Cavazzoni, director of the Center for Drug Evaluation and Research (CDER), cited plans at the FDLI meeting for advisory committee “modernization” among numerous key initiatives for her office in the coming months. The process will include efforts to refine the selection of advisors so that their “expertise applies precisely to the matters under consideration.” That may involve adding to advisory panels more temporary members with special knowledge about the drug or disease under discussion and taking steps to ensure diversity in geographic areas represented.

Cavazzoni also noted the need for FDA to improve how it communicates about advisory committee operations and their relationship to the agency. This involves emphasizing to the public that these panels play an advisory role to the agency—and that FDA retains ultimate decision-making authority.

FDA’s interest in updating advisory committee composition and operations has become more visible in recent months, stemming from the uproar that resulted when FDA granted accelerated approval in 2021 to Biogen’s Alzheimer’s treatment, Aducanumab, despite a near-unanimous vote against approval at an advisory meeting in November 2020. Three panel members resigned in protest, and Medicare limited coverage to those patients participating in ongoing clinical trials.

That controversy, and subsequent heated debates over the approval of other treatments for critical diseases with questionable efficacy data, has prompted FDA officials to reconsider the advisory committee process, including the composition of the panels and the issues identified for discussion. A main change would be to shift away from “gladiator votes”—yes-or-no decisions on specific applications—and to provide more nuanced opinions on the main issues. But in some cases, the absence of up-or-down votes on key questions may generate confusion as to what the committee experts actually recommend. In the recent consideration of Sarepta’s new gene therapy to treat Duchenne’s muscular dystrophy, the advisory committee supported approval by a very slim margin. However, the patient advocate on the panel made a strong case for FDA to approve the drug as another treatment option for this devastating condition. FDA staff has gone back to the drawing boards, indicating it may limit treatment to a very young age group pending further clinical results.

Interchange among outside experts on scientific and technologic questions is important, Califf emphasized at the FDLI meeting. Such debate “makes our decisions better,” he noted, and “adds a level of transparency.” However, the commissioner also raised concerns about the steady stream of “misinformation and disinformation” in society that can undermine public confidence in science and “weaken faith in governmental and other institutions, including the FDA.”

Public debate among expert advisors can both support sometimes controversial decisions by FDA staffers, but also raise challenges to agency actions. The advisory committee process is one element in this ongoing debate that appears open to improvement, and Califf advised the regulatory community to “stay tuned for developments in this area.”

https://www.fda.gov/news-events/speeches-fda-officials/remarks-commissioner-robert-califf-2023-food-and-drug-law-institute-fdli-annual-conference-05172023

Washington Correspondent and can be reached at

Agency hopes to update and improve its advisory committee composition and operations—to help FDA scientists “get the best advice possible.”

FDA Eyes Advisory Committee Reform to Enhance Credibility

Şebnem Yaşaroğullari works as VP of clinical operations for Mene Research 

David Rolando is a biostatician for Axelys Santé

Lamine Mahi is the CEO of Axelys Santé. 

Martine Dehlinger-Kremer, PhD, President, EUCROF and VP Scientific Affairs, Pediatric SME, ICON Plc.

Şebnem Yaşaroğullari, VP, clinical operations, Mene Research

Helena Lüning, study start-up manager, ICON PLC

Clinical research is necessary for the development of new health products. The evaluation of the safety and efficacy of new drugs or devices in patients is already governed by numerous regulations. Furthermore, speed requirements and competition between the various pharmaceutical and biotech companies are also factors in the dynamics of the industry. All these aspects intensified during the outbreak of the COVID-19 pandemic which was an opportunity to exemplify the unique role that Clinical Research Organizations (CROs) play in clinical research due to their expertise and ability to rapidly adapt and respond to a changing environment.

The COVID-19 pandemic had a significant impact on the activity of CROs and many of them had to suspend or delay clinical trials due to the pandemic, as well as the fact that many of their staff were unable to travel to sites due to travel restrictions. This halting led to a reduction of patient enrollments and difficulties for on-site monitoring.

 Additionally, the pandemic caused a disruption in the supply chain for clinical trial materials, as well as the availability of laboratory services, which further complicated the conduct of clinical trials. As a result, many CROs have had to move toward offering virtual services that can be performed remotely, such as patient recruitment, monitoring, data management, and statistical analysis, in order to continue the important work of researching novel and important medicines.

A survey involving the European CRO Federation (EUCROF) was conducted between July and September 2022 with its affiliated CROs in order to determine how the COVID-19 pandemic impacted their clinical research services.

 A total of 52 responses were received and 77% of the participating CROs stated that the COVID-19 pandemic caused changes in their internal organization and 75% reported that this pandemic induced negative impact on their ongoing trials.

The main negative impacts were the discontinuation or slowing down of recruitment of new trial participants (92%), cancellation or postponement of on-site monitoring visits (77%), temporary halt of the trial at some of all trial sites (69%) and cancellation of patient visits as the trial participants cannot reach the site (62%).

 Negative impacts on clinical research encountered in CROs during the COVID-19 pandemic.

David Rolando, biostatistician, Axelys Santé

CROs quickly adapted their services to counter this phenomenon. Telemedicine, which is a form of remote medical practice using information and communication technologies, has been massively deployed in Europe and overall. As an example, in France, 67 studies based on telemedicine and currently recruiting or not yet recruiting are registered on the Clinicaltrials.gov website, making France the

first country in Europe to implement telemedicine massively in its clinical research.

In this survey, the main measures taken to reduce the negative impact of the COVID-19 pandemic were the conversion of physical visits on site into phone or video visits (82%) and extension of the duration of the trial (82%).

The European Medicines Agency published guidelines on “Guidance on the management of clinical trials during the COVID-19 (coronavirus) pandemic”

; 83% of the respondents of the survey were aware of these guidelines and 97% implemented them. A total of 93% of respondents thought that these guidelines were useful to improve their business in this context.

CROs role in COVID-19 vaccines and treatments

CROs played a critical role in the COVID-19 clinical trial race. They provided expertise in the development of clinical trial protocols, and they helped to ensure that the trials adhered to all local, national, and international regulations. CROs were also responsible for managing the logistics of the trials, including recruitment of sites, patient enrollment, data collection, and data analysis. Finally, CROs were also responsible for the strategy of the development of the new medicines helping biotech companies with limited experience in drug development.

The development of a vaccine against the SARS-CoV-2 in 2020 resulted of an international effort as never seen before. This effort contributed to the development of several vaccine candidates, such as Comirnaty® (Pfizer-BioNTech) and Spikevax® (Moderna), within a year, whereas other vaccines typically took several years to develop in the past.

 This was partly allowed by regulatory authorities (FDA6 and EMA7) who updated their guidelines regarding COVID-19 vaccine development to facilitate the regulatory processes during the pandemic, but also by the rapidity of CROs in proposing services of clinical research and drug development expertise to pharmaceutical companies. Indeed, CROs have played a critical role in the execution of vaccine studies for COVID-19, providing clinical trial support services, such as site selection, sample collection, and data management. CROs have enabled vaccine developers to quickly initiate and execute clinical trials, helping to accelerate the development of vaccines and drugs such as remdesivir. CROs have also helped coordinate global clinical trials, allowing for the timely collection of data from different countries and completion of clinical trials.

In the survey cited above, 65% of CROs reported to have participated in COVID-19 trials in 2020–2022 and almost a majority participated to two studies (41%; n=5–10 studies for 21% and >10 for 29%). Most of these studies included more than 100 patients.

Number of patients/participants in COVID-19 studies managed by CROs in 2020–2022.

Most of these studies were large studies, involving thousands of participants and were essentially drug (59%) and vaccine (53%) COVID-19 studies (

). About half of the CROs participated in vaccine studies (one or two studies in majority, involving hundreds of patients). The vast majority of these studies were performed in Europe.

Types of studies on COVID-19 performed by CROs in 2020–2022 (more than one answer possible).

Despite the COVID-19 crisis, CROs have been able to be innovative to avoid disruption in clinical research and therefore they played an important role in the development of COVID-19 vaccines studies. Thus, 69% of the CROs surveyed in the cited EUCROF survey have implemented new digital tools (e.g., telemedicine, remote monitoring) within the context of the COVID-19 pandemic and they all consider they will keep them once the pandemic is over. A total of 35% of CROs conducted more than 50% of their monitoring visits remotely. Even though CROs have used new digital tools, they generally (83%) did not actively participate in the development of health mobile applications.

CROs were heavily involved in COVID studies, but for 70% of those surveyed in the EUCROF survey, this activity represented less than 10% of their business. They considered that the biggest challenges during COVID-19 pandemic was set-up, conduct and follow-up of clinical studies (e.g., recruitment, data collection (77%), business development, interactions with partners and clients (44%) and development/adaptation to new working tools e.g. videoconference, remote monitoring (34%)).

CROs are essential in providing the necessary expertise, resources and support to carry out clinical research and bring new drugs to market. CROs can help improve quality, create efficiencies and reduce timelines, making them an invaluable part of the drug development process. The COVID-19 pandemic allowed CROs to show flexibility and innovation despite physical obstacles. They were able to maintain the ongoing clinical research in particular by using new technologies in a shortened timeframe to meet an urgent public health demand. CROs have been a key contributor to the development of new medicines in a very short period of time during the COVID-19 pandemic. Their ability to be agile and drive innovation will position them as the trusted partner for drug development as the clinical research industry continues to evolve.

1. Tuttle KR. Impact of the COVID-19 pandemic on clinical research. Nat Rev Nephrol. 2020;16:562-4.

2. Sathian B, Asim M, Banerjee I, et al. Impact of COVID-19 on clinical trials and clinical research: A systematic review. Nepal J Epidemiol. 2020;10:878-87.

3. Harrison F, Coladangelo, Heutte M, Hardman TC, Marini S (2022). Impact of the COVID-19 Pandemic on Clinical Trial Conduct: Lessons for the Future [Preprint]. doi:10.21203/rs.3.rs-1118410/v1.

4. La France est le pays européen avec le plus d’essais cliniques en télémédecine. Télémédecine 360. Published July 28, 2015. Accessed June 1, 2022. 

https://www.telemedecine-360.com/la-france-est-le-pays-europeen-avec-le-plus-dessais-cliniques-de-telemedecine/

5. European Medicines Agency. Guidance on the management of clinical trials during the COVID-19 (coronavirus) pandemic. Version 5 10/02/2022. 

https://health.ec.europa.eu/system/files/2022-02/guidanceclinicaltrials_covid19_en_1.pdf

6. Wibawa T. COVID-19 vaccine research and development: ethical issues. Trop Med Int Health. 2021;26:14-9.

7. Food Drug Administration. COVID-19 Vaccines.Published online May 27, 2022. Accessed June 1, 2022. 

https://www.fda.gov/emergency-preparedness-and-response/coronavirus-disease-2019-covid-19/covid-19-vaccines

8. European Medicines Agency. COVID-19 vaccines: development, evaluation, approval and monitoring. European Medicines Agency. Published October 27, 2020. Accessed June 1, 2022. 

https://www.ema.europa.eu/en/human-regulatory/overview/public-health-threats/coronavirus-disease-covid-19/treatments-vaccines/vaccines-covid-19/covid-19-vaccines-development-evaluation-approval-monitoring

The adaptability and innovative capacity of CROs highlighted in EUCROF survey.

COVID-19 Pandemic Exemplifies the Benefits of CROs

In a presentation at Outsourcing in Clinical Trials East Coast 2023, Harsha K. Rajasimha, PhD, founder and executive chairman, IndoUSrare, and former guest of the 

, discussed what industry must do to achieve diversity, equity, inclusion, and access (DEIA) in clinical trials.

To begin, Rajasimha pointed out that the access portion has “gone missing.” Of the major considerations typically taken into account in clinical trials: patient recruitment and retention, managing protocol complexity and amendments, vendor management, and manual repetitive tasks and errors; all of which are overshadowed by cost, diversity is often left out.

Harsha Rajasimha, MS, PhD, Founder and Chairman, IndoUSrare

What are the largest barriers to achieving DEIA in clinical trials? Geographic location is a major pain point, which is nothing new to industry. There often isn’t alignment on complex cultural barriers such as language, religious beliefs, and dietary restrictions. A lack of data for all diversity parameters, especially in rare diseases, as well as mistrust among diverse populations are also major barriers.

Rajasimha addressed that one of, if not the largest issue within mistrust among diverse populations is that they are less frequently asked to participate in trials.

How can these paint points be addressed to work towards achieving DEIA in trials? It starts with regulatory policies, mandates, and guidelines. There also must be a commitment among all stakeholders with a shared goal. This includes global thinking and cross-border collaboration as well as more inclusive digital and data platforms. An overarching solution is implementing next generation training and education programs for cultural competency for clinical trial stakeholders.

While the COVID-19 pandemic disrupted many aspects of the clinical trials industry, it has provided the opportunity for stakeholders to reflect on pain points such as diversity. Rajasimha concluded by noting that industry has never been so open to new ideas and technology. The time to make clinical trials more accessible is now.

Harsha K. Rajasimha, PhD, founder and executive chairman, IndoUSrare, provides the OCT audience insights into better achieving DEIA clinical trials.

OCT East 2023: Achieving Global DEIA in Clinical Trials

In this discussion with Craig Lipset, a recognized leader in the field of clinical trials, we delve into the recent closure of 

. Lipset provides valuable insights into the complexities and challenges of managing clinical trials within a retail pharmacy setting. He examines CVS's decision in the broader context of the pharmaceutical industry, explores potential impacts, and speculates on alternative models that could shape the future of clinical trials.

Moe Alsumidaie: There's been substantial chatter regarding CVS's decision to close its clinical trial unit. Could you provide some insight into what could have possibly happened behind the scenes, given your extensive experience in the field?

Thanks, Moe. CVS is the largest healthcare company in the United States. Companies like CVS have high expectations for new business areas to be meaningful sources of revenue. Some have speculated that "trials were too hard," but CVS had hired very experienced leaders from CROs and pharma that were "eyes wide open" to the challenges of running studies. In fact, they had built a very respectable pipeline and had developed a positive reputation among sponsors for delivering quality. But most new providers of solutions for clinical trials take years before they can reach even $25 million to $50 million in revenue, and given CVS's interests and priorities in primary care, it seems clinical trials were not going to be able to compete for attention and support. There are many very talented clinical trial professionals that worked to make the trials business work with high quality at CVS, and this decision seems to be based solely on economics and priorities. For those of us who have worked in large corporations, we have seen no shortage of examples of C-suite decisions made despite things working well in the trenches. 

MA: CVS's involvement in clinical trials isn't a first for retail pharmacies, is it?

: Correct, Moe. In fact, we can look back over the past decade. Way back at DPharm 2013, John Orloff presented on work his team at Novartis was doing with Walgreens to run vaccine trials in the store. In fact, at Pfizer, we had planned our follow-on to the REMOTE trial as one meant to run inside Walgreens. But the investment and commitment at the time were not substantial, and when other corporate priorities emerged, Walgreens backed away from trial conduct.

Some will also recall work that McKesson had also published in 2013 together with Ken Getz at Tufts, where they showed strong support for clinical trial enrollment supported by the pharmacist.

In truth, CVS activity in clinical trials pre-dated the pandemic. Many pharma had worked with CVS and other pharmacies to support patient recruitment based on pharmacy data, typically running letter-based campaigns to patients. The Aetna business inside CVS had a real-world data company called Healthagen that had also supported life sciences and research for years. CVS acquired Coram back in 2014, which included Coram's clinical trial business of offering home health visits for clinical trials. What was new was bringing these pieces together and working to enable study conduct inside the store. The closure of the clinical trials unit at CVS then represents a loss of not only new capabilities but also some capabilities that have served the industry well for years.

MA: It certainly sounds like a significant loss. However, the fact that CVS had successfully offered these services for years and still decided to close its clinical trial unit is somewhat puzzling. What do you think this means for the future?

 Following the CVS entry into trials, we have seen Walgreens and Walmart, and more recently, Kroger and others take an interest in clinical trials. Some have worried that the CVS exit will lead to others backing away. I do not share this concern. Each has different strategies – some are more focused just on recruitment, which is more accessible. Others, such as Walgreens, have positioned clinical trials as a health equity priority, which may give them more flexibility to make an impact over time.

MA: Decentralized Clinical Trials (DCTs) are essential, given FDA's new guidance, and retail pharmacies seemed like an ideal platform for expansion and diversity. In your opinion, which other organizations are suited for this model?

 I am very keen to see if and when companies such as LabCorp and Quest consider entering their patient service centers as locations for study conduct. They are more focused on clinical services than typical retail locations and often embedded in communities, and they have waiting rooms and people in white coats rather than mixing trials in a traditional retail setting. Retail will have its place for some, but more doors are needed. As we see increased use of video to enable the investigator to "see" their patients from other locations (labs, community physician offices), we will continue to see more locations unlocked for access.

MA: That's a fascinating outlook. So, you're envisioning a future for clinical trials that leans more towards unconventional sites and virtual interactions.

 First, we will still have a core focus on the clinical trial site as we know it today, just further supported and enhanced with decentralized tools that improve access. But we know our existing site capacity is not adequate to help ensure equitable access to research participation. And so, we will still need other stakeholders – pharmacy, labs, and mobile units. The FDA draft guidance on DCT also takes an important step to define new roles for healthcare providers to support trials, and I am keen to see how we can unlock every doctor's office as a "host location" for a study investigator to see a participant powered by video.

MA: Let's shift gears a bit and talk about the impact of CVS's decision on patients. How do you think this closure might affect them? And how would this shift towards organizations like LabCorp or Quest impact patient experience?

 It is my understanding that CVS is continuing to support sponsors with studies enrolling patients in the near term and for longer studies that are ensuring patients are migrated to an appropriate site. Ideally, no patient should feel cut off or abandoned if they were engaged in a trial through CVS. But this is certainly a lost opportunity going forward, as CVS has a substantial footprint to have helped inform patients about research opportunities going forward. That said, this certainly leaves even more room in the market for others – whether pharmacies like Walgreens, Walmart, and Kroger, labs like LabCorp and Quest, or others.

MA: Indeed, patient-centricity is key. Lastly, Craig, given all these developments and potential shifts, how should pharmaceutical companies position themselves to adapt?

 Many pharma sponsors invest time and energy to engage with innovative new partners. Whether through executives in development operations or clinical operations or through dedicated "clinical innovation teams," tracking and engaging a partner can take substantial effort. It can be defeating when a team has identified and engaged a partner like CVS, including the effort to build support and advocacy among leaders and other lines within their company. This is a reminder for pharma sponsors of the importance of resilience and agility. Momentum begun with a partner like CVS can be sustained with new partners, and teams have to remain agile to flex and adapt when changes such as these take place.

Our current models for research are unsustainable, and for too many people, they are inaccessible. Investments to make trials more patient-friendly, more accessible, and more digitally enabled are the right direction for the near term and the long term.

In this Q&A, Craig Lipset offers additional insights following the announcement that CVS will be closing its clinical trial services business by the end of the year. 

CVS's Closure of Its Clinical Trial Unit and What it Means for The Future

Allucent announced that it has partnered with THREAD to launch Allucent Patient Direct Trials. The new offering brings technology, development, and regulatory expertise to small and emerging biotechnology companies to support them in designing and overseeing customized decentralized clinical trial (DCT) approaches that address their needs.

Allucent Patient Direct Trials leverages this experience to address the needs of many small and emerging biotech companies that may not have the in-house resources required to design and oversee DCTs. Working with THREAD, Allucent's team of regulatory and product development consultants can guide sponsors in determining the most effective and efficient digital strategies for remote engagement and data collection for their studies.

Allucent Launches Decentralized Clinical Trial Solution at 2023 World Orphan Drug Congress. 

Allucent partners with THREAD to launch Allucent Patient Direct Trials, a DCT offering focused on small and mid-sized biotech companies.

Allucent Launches Decentralized Clinical Trial Solution

Suvoda has announced the general availability of its electronic clinical outcome assessments (eCOA) product that delivers simplified questionnaire licensing and localizations, streamlined device logistics, and improved data integrity. Click to tweet.

Suvoda eCOA is delivered on a single platform with Suvoda IRT and eConsent, and is designed to work with these products to help clinical trial sponsors and sites manage complex clinical trials and focus more time on patient interactions.

Suvoda Announces General Availability of Powerful New eCOA Solution

New solution delivers simplified questionnaire licensing and localizations, streamlined device logistics, and improved data integrity.

Suvoda Announces General Availability of New eCOA Solution

Veeva Systems has announced a collaboration with UCB, whereby the pharma company will adopt Veeva's ePRO and eConsent solutions, to provide a patient-centric, digital experience to study participants.

Veeva ePRO offers the design, management, and completion of electronic patient-reported outcomes (ePRO) with data flow among sponsors, sites, and patients. Veeva eConsent offers the set-up, completion, and review of consent for patients, sites, and study teams. Both applications are available to patients through MyVeeva for Patients, which provides access for participants clinical trial activities, scheduling, and communications. Veeva ePRO and Veeva eConsent are part of Veeva Vault Clinical Suite, a set of integrated capabilities for both clinical operations and clinical data management.

UCB and Veeva Collaborate to Advance the Patient Experience in Clinical Trials. 

UCB will adopt Veeva ePRO and Veeva eConsent.

UCB and Veeva Announce Collaboration

VIDA Diagnostics has released a cloud-based case viewer, designed to enhance clinical trial imaging workflows. Users of the VIDA Intelligence Platform can now view clinical trial imaging cases directly in a web browser to review imaging and clinical data. This new capability will streamline quality-controlled data curation as cases and reader impressions are added to the digital biobank.

The case viewer will have an impact on several clinical trial imaging workflows, including:

Quality control: Members of a trial team will now have access to view the images collected, incorporating a visual quality control step into the workflow to ensure only high-quality data is added to the digital biobank.

Eligibility reads: Radiologists can view images and assess patients’ imaging data for clinical trial eligibility. Eligibility results are made available to trial team members in real-time within the trial imaging management platform.

VIDA Launches Cloud-Based Case Viewer to Improve Clinical Trial Imaging Workflows. 

New capability added to VIDA Intelligence Platform will streamline quality-controlled data curation.

VIDA Launches Cloud-Based Case Viewer

While many big pharma companies have shied away from the cardiovascular space, and even fewer smaller biotechs are venturing into it, NewAmsterdam Pharma stands as a notable exception. In this interview, John Kastelein, MD, founder and chief scientific officer, delves deep into the challenges and opportunities within the cardiovascular field, exploring the current landscape for lipid-lowering therapies and the unique potential advantages of CETP inhibitors. The conversation covers various aspects of clinical trial design, emphasizes the importance of diversity and inclusion in trial enrollment, and reflects on lessons learned from the COVID-19 pandemic. Additionally, Kastelein shares his perspective on why the company has chosen to invest in its own Phase III trials instead of pursuing acquisition.

Moe Alsumidaie: Given the global concern for cardiovascular health and the crisis driven by factors like obesity, why are relatively few biopharmaceutical companies working in this space?

 The rising rates of cardiovascular disease and death in the US can be partly attributed to therapeutic inertia, where patients and doctors struggle to adhere to and implement guidelines. Expensive new drugs, such as monoclonal antibodies to PCSK9, and inexpensive but less potent generics like ezetimibe have left little room for new development. Also, companies find it difficult to introduce drugs that offer significant benefits over existing generics to justify payers to cover the costs.

MA: Can the success seen in the diabetes space, with many new medications and no therapeutic inertia, be replicated for blood pressure and lipid management?

 Yes, it should be possible for blood pressure and lipid management, but we still need to see that happen. We believe that obicetrapib, our CETP inhibitor, has the potential to partly address some of the questions in the lipid space.

MA: With your extensive experience in cardiovascular studies, can you explain how trial designs have evolved to generate better outcomes compared to the past?

. The major change is that new drugs must be tested on top of statin therapy. However, some mistakes have been made in the past that can be corrected now. For instance, cardiovascular outcomes trials need to last at least four years for lipid lowering to see significant changes in endpoints.

MA: What barriers do you face as a small company trying to enter the cardiovascular space?

 One of the main challenges for investors and small companies is the cost of clinical trials. FDA requires large Phase III lipid programs and outcomes trials, making the costs quite significant. However, we are committed to approving our drug. We believe our current cash balance will be sufficient to fund our operations through the expected completion of our ongoing trials and demonstrate that our drug lowers cholesterol and reduces heart attacks and strokes.

MA: Smaller pharma companies usually pursue acquisition rather than investing in their own Phase III trials. Why did you choose the latter?

 We chose to invest in our own Phase III trials because we believe the true value of our compound will only become apparent after the completion of the two lipid-lowering Phase III trials. We believe our drug has unique properties, with potential benefits in diabetes, Alzheimer's, and other conditions, along with its potent LDL-lowering capability. We think that the full potential of our drug can only be appreciated after large-scale trials that demonstrate its efficacy and safety. Our management team has extensive experience in this area, which gives us confidence in our ability to successfully execute the trials ourselves and maximize the value of our compound.

MA: Considering the current landscape for lipid-lowering therapies, what unique benefits does the CETP inhibitor offer that would justify its inclusion in payer formularies and differentiate itself from existing therapies in the market like the SGLT2 inhibitors?

 Our CETP inhibitor is very potent at a low dose of 10 milligrams, making it appealing for our target demographic with a mean age of 70. Additionally, our drug has been generally well tolerated in clinical trials to date, is cost-effective to produce, and is designed to be taken as a small tablet once a day. We have learned from past challenges in trial design and have taken great care in designing our Phase III program and our cardiovascular outcomes trial differently, hopefully ensuring its success.

MA: What unique benefits does the CETP inhibitor offer compared to existing therapies like SGLT2 inhibitors?

 Our CETP inhibitor has several advantages. It is very potent at a low dose of 10 milligrams. In our ROSE Phase IIb trial, patients receiving our CETP inhibitor at 10 mg showed a median reduction of LDL-C of 51% versus baseline in patients who were on a high-intensity statin therapy. When given the CETP inhibitor at 10 mg in combination with ezetimibe in the ROSE2 trial, we saw even greater reductions in that population. These data are appealing for our target demographic, who are mainly elderly people. The small pill is convenient for daily use and can be taken with or without food. Additionally, the drug is inexpensive to produce, which allows for flexible pricing attractive to payers. Furthermore, we plan to study the CETP inhibitor’s protective effects against diabetes and possibly also against Alzheimer’s disease. This range of potential benefits makes it a promising option for patients.

MA: How have you ensured your clinical trials last long enough and target high-risk patients? How has the COVID-19 pandemic influenced your trial designs?

 We have stipulated that our outcomes trials should last at least 2.5 years after the last patient enrolls, totaling about 4 years. To enrich our trials, we have selected patients with conditions such as elevated triglycerides, diabetes, and recent coronary disease. During the pandemic, we were also able to address underrepresented communities, such as African Americans and other demographics in our trials, achieving our intended diversity goals. Conducting cardiovascular outcomes trials during the pandemic was challenging for the industry, but fortunately, the bulk of NewAmsterdam’s ongoing outcomes trial has taken place after the worst of the pandemic.

, MBA, MSF, is a thought leader and expert in the application of business analytics toward clinical trials, and regular contributor to Applied Clinical Trials.

In this Q&A, John Kastelein, MD, founder and chief scientific officer, NewAmsterdam Pharma, discusses the challenges and opportunities within the cardiovascular field, exploring the current landscape for lipid-lowering therapies and the unique potential advantages of CETP inhibitors. 

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