Weekly April 12, 2021

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COVID-19 Update…2 Industry Briefs …4 Up and Coming…6 Sites Push Back on the Burden of Handling Drug & Device Pipeline News…10 Sponsors’ Unnecessary Safety Reports Forty-four drugs and devices have entered a new trial phase this week. By Charlie Passut “Sites are really starting to take a stand,” Research Center Spotlight…13 ponsors are overwhelming sites said Steven Beales, senior vice president with a growing volume of safety for WCG’s scientific and regulatory division. reports, and sites are fighting back. “Some of the biggest [academic] sites S VIRTUAL WORKSHOP The magnitude of the problem of un- are coming back to sponsors and saying necessary and overly burdensome safety enough is enough. We’re going to see Effective Root Cause Analysis and CAPA Investigations for reporting is getting worse; in the past more and more of this pushback from the Life Sciences three years, some sponsors of oncology nonacademic sites if sponsors don’t do Tuesday, June 22 - Thursday, June 24, 2021 drugs have unleashed a five-fold increase something,” Beales said. Presented by WCG FDAnews and in safety reports. Part of the problem is that some spon- ValSource Learning Solution Safety reporting procedures have always sors and CROs do not differentiate between REGISTER TODAY been a time-consuming challenge for sites, adverse events caused by the investigational but sponsor and CRO safety reports that product and those related to factors outside FREE WEBINAR duplicate information or are not needed the trial, classifying everything as requiring APRIL increase the workload for staff who need to documentation in a suspected unexpected process the reports. The rising complexity of serious adverse reaction (SUSAR) report. 15 trials and the growing number of oncology “Sponsors think they’re following the letter Five Telltale Signs You’re Ready trials is amplifying the problem. see Unnecessary Safety Reports on page 7 » for an Electronic TMF System

Deputy Commissioner Says FDA Working at Sponsored by REGISTER Top Speed to Develop RWD Skills Agatha, Inc. By Charlie Passut familiarity with working with RWD to create ore than 60 percent of current an inclusive approach that weighs the total- drug submissions to the FDA ity of the evidence. M include real-world data (RWD) in “You may think that we’ve known the some form, and agency officials are saying scientific methods for observational research the FDA needs to expedite honing its skill set for a very long time, but in fact these data- in regulating the use of it in trials. sets are different,” Abernethy told attendees Amy Abernethy, principal deputy com- of the Pharma Clinical 2021 Conference missioner for food and drugs at the FDA, last week. “We need to develop definitions said the agency needs to strengthen those for variables within the datasets that are skills as soon as possible. “RWD is becoming common and well-understood across differ- Without a working knowledge progressively more common and important,” ent datasets. We need to develop ways of of EU privacy laws and regulations, she said. working with datasets when the informa- you run the risk of not being compliant. Abernethy said the FDA is learning tion is rapidly accumulating and also when If your clinical trials how to analyze real-world datasets better the day-to-day delivery of care is adjusting involve the personal data and how to incorporate them as part of an across time. And we really need to be able of EU-based individuals, you need to understand overall evidence package. But she said the to rapidly convey the methods as they the rules that apply to Data Privacy in the EU see Develop RWD Skills on page 8 data collection. agency still needs to develop a comfort and » A Guide for Clinical Trial Sponsors and Sites ORDER TODAY Vol. 25, Issue 15. Copyright © 2021 by WCG CenterWatch CenterWatch Weekly April 12, 2021 2 of 13 COVID-19 Update

COVID-19 Drug Research found that the nasally administered anti-CD3 COVID-19 Vaccines: Roundup antibody treatment was well-tolerated and Johnson & Johnson (J&J) is now dosing COVID-19 Therapies: associated with reduced pulmonary and sys- adolescents with its COVID-19 vaccine can- Eli Lilly’s and Incyte’s Janus kinase (JAK) temic inflammation. Treatment with Foralum- didate Ad26.COV2.S in an ongoing, placebo- inhibitor Olumiant (baricitinib) proved unable ab in this prior study reduced several markers controlled phase 2a trial. The randomized to significantly reduce progression to nonin- of inflammation, including C-reactive protein trial was launched in September and initially vasive ventilation for COVID-19 patients in a and interleukin-6. Another recent study from included healthy adults between 18 and phase 3 trial, though the drug still managed Harvard Medical School and a Brazilian CRO 55 years of age as well as individuals 65 to significantly reduce the risk of death. The also found that Foralumab reduced pulmo- years and older. The amended protocol now companies announced last week that the nary and systemic inflammation. includes adolescents and teenagers between phase 3 study didn’t meet its primary end- Sound Pharmaceuticals is planning to 12 and 17 years of age. Currently, the study is point, with only 2.7 percent of patients given launch two phase 2 trials to study SPI-1005, enrolling participants from the UK and Spain, the JAK inhibitor proving less likely than those an oral capsule comprising small-molecule but J&J expects to soon start enrollment who received standard of care to progress to ebselen, in patients with moderate-to-se- in the U.S., Canada and the Netherlands. In ventilation or death, a finding that was not vere COVID-19. While the therapy was devel- February, the FDA granted an Emergency Use statistically significant, the companies said. oped for neurotologic, neuropsychiatric and Authorization (EUA) to the company’s single- Grifols has announced that its investi- respiratory indications, a Cooperative Grant dose version of its vaccine, but this authoriza- gational immunoglobulin therapy CoVIg-19 award of $3.1 million from the National tion restricts the use of the vaccine to adults. showed no benefit in 593 hospitalized adults Institutes of Health’s National Center for The EUA was based on findings from the with COVID-19 who participated in the phase Advancing Translational Sciences has pro- phase 3 ENSEMBLE trial, which showed the 3 INSIGHT-013 trial. The therapy, which con- vided an incentive for Sound to investigate vaccine was 66 percent effective at prevent- sists of antibodies from patients who have SPI-1005 in treating the novel coronavirus. ing moderate-to-severe COVID-19 approxi- recovered from COVID-19, was developed in A total of 120 patients with moderate-to- mately four weeks following vaccination. partnership with Takeda Pharmaceutical, severe COVID-19 will be enrolled in the The University of Oxford is pausing a trial CSL Behring, Emergent BioSolutions and two randomized, placebo-controlled trials. evaluating AstraZeneca’s COVID-19 vaccine other companies involved in the CoVIg-19 Patients will receive either SPI-1005 or pla- in children and teenagers after concerns Plasma Alliance. The late-stage trial was con- cebo for up to seven or 14 days. The primary were raised that the vaccine may be associ- ducted across 63 sites in the U.S. as well as 10 outcome is the number of participants with ated with rare cases of blood clotting. Back other countries. The investigators assessed treatment-related adverse events. Additional in February, researchers of the study started whether the plasma treatment reduced the secondary study outcomes include clinical to recruit 300 people between the ages of risk of COVID-19 progression when added to improvement and degree of supplemental six and 17 years who were to receive the standard of care, including Gilead Sciences’ oxygen required during treatment. AstraZeneca vaccine or a control meningitis remdesivir. There was no difference between Findings from a phase 1 study show that vaccine. The UK’s Medicines and Healthcare patients who received CoVIg-19 vs. standard UNION therapeutics’ COVID-19 inhaled products Regulatory Agency (MHRA) is now of care only in regard to clinical status at day and intranasal niclosamide candidates are recommending that people under the age seven. Following the announcement of the safe when administered to healthy people. of 30 try to get a different vaccine if pos- study results, the CoVIg-19 Plasma Alliance The study included 44 healthy participants sible. Previously, the MHRA had said that the announced it plans to disband. who were randomized to either one of the benefits of the COVID-19 vaccine outweigh Tiziana Life Sciences announced it will UNI911 candidates (UNI91103 or UNI91104) the potential risks. The World Health Orga- soon launch a phase 2 trial for Foralumab, the or placebo. The trial met its endpoints and nization has also echoed these sentiments. company’s nasal anti-CD3 human monoclo- demonstrated that the niclosamide solution The European Medicines Agency has not nal antibody, in hospitalized patients with was well-tolerated when administered both identified a causal association between moderate-to-severe COVID-19. The random- intranasally and through inhalation. There was AstraZeneca’s COVID-19 vaccine candidate ized, placebo-controlled trial will be conduct- no indication of systemic accumulation of the and blood clots. ed in Brazil. Patients enrolled in the study will products in the blood. These findings pave the A phase 2 study led by the NIH’s National receive standard-of-care background therapy way for future studies that will examine the Institute of Allergy and Infectious Diseases is with or without Foralumab. A previous study prophylactic and treatment efficacy of these looking to assess the risk of allergic reactions in patients with mild-to-moderate COVID-19 drug candidates in patients with COVID-19. continues on next page » Copyright © 2021 by WCG CenterWatch CWW2515 CenterWatch Weekly April 12, 2021 3 of 13 COVID-19 Update (continued from page 2) in patients who have received the Moderna insight into whether the currently authorized participants who elect to receive additional and Pfizer/BioNTech COVID-19 vaccines. COVID-19 vaccine prevents symptomatic injections will receive an additional two-dose The trial will be performed across 35 academ- and severe COVID-19 in adults. The study will regimen of the vaccine if they originally ic allergy research centers in the U.S. and will also seek to determine whether an individual received the placebo or an additional dose recruit up to 3,400 adults between 18 and can become infected following vaccination. of the placebo if they originally received the 69 years of age. The majority of participants The study will include up to 12,000 college active vaccine. In the South African trial, par- in the study (60 percent) will have a history students between the ages of 18 and 26 from ticipants will receive the vaccine if they had of severe allergic reactions or a mast-cell dis- more than 20 U.S. universities. Participants originally received a placebo or a booster dose order diagnosis. The other 40 percent of the will be followed over a five-month period. of the active vaccine if they had received only study population will include individuals with Half of the cohort will be randomized to the active vaccine. Participants will remain no history of allergic reactions or mast-cell receive the vaccine at the time of enrollment, blinded to their treatments throughout the disorder. Up to two-thirds of participants in and the other half of participants will receive trial. Safety and durability of the vaccine will each study group will be women, given that the vaccine approximately four months later. be assessed over a two-year follow-up period. females tend to experience the most severe Around 25,500 people who are considered Bharat Biotech is launching clinical trials allergic reactions to the vaccines. “close contacts” of the study participants will to study whether a third dose of Covaxin, An early-stage NIH trial is investigating also be invited to participate in the trial so the company’s COVID-19 vaccine, is an the immunogenicity and safety of Moder- the researchers can examine the rate of viral effective booster shot when administered na’s investigational mRNA-1273.351 vaccine transmission from vaccinated people. six months following the second vaccine developed to protect against the B.1.351 A COVID-19 vaccine candidate devel- dose. The Drugs Controller General of India’s variant of SARS-CoV-2. The new variant oped by the University of Texas at Austin subject expert committee gave permission vaccine delivers instructions for making the and Mount Sinai Hospital, is headed for to the company to test this booster shot in SARS-CoV-2 spike that includes mutations in phase 1/2 clinical trials. The candidate, called an amended phase 2 trial. Only participants the B.1.351 SARS-Cov-2 variant. The phase 1 NDV-HXP-S, was developed using methods who have received 6 micrograms of the vac- study plans to enroll up to 210 healthy adults similar to those used to develop influenza cine will receive the third dose. According at four sites in the U.S. Moderna says it plans vaccines. According to the researchers who to the company, the 6-microgram dose was to test mRNA-1273.351 in animal models developed the vaccine, the new candi- chosen because this demonstrated better concurrently with the phase 1 clinical trial. date can be stored at regular refrigerator immune responses. Last month, Bharat Participants aged 18 years and older in this temperatures and can be developed faster presented initial results of its phase 3 trial, trial must have already received Moderna’s and cheaper than other leading COVID-19 which showed Covaxin was 81 percent ef- mRNA-1273 vaccine, but a subgroup of pa- vaccines. The two-phase study will enroll fective for protecting against COVID-19. tients between 18 and 55 years of age who 210 healthy participants who will receive the A nanoparticle COVID-19 vaccine devel- have not received a COVID-19 vaccine are vaccine candidate at different doses without oped by the U.S. Army has entered phase also eligible to participate. Study volunteers adjuvant and at two different doses with 1 clinical research. The vaccine features a will be randomly assigned to one of eight co- an adjuvant. Endpoints will include safety, flexible approach capable of targeting several horts featuring varying doses of the vaccine. tolerability and immunogenicity. Following SARS-CoV-2 variants and possibly other coro- Fred Hutchinson Cancer Research Center’s the completion of an interim analysis of the naviruses. The vaccine, dubbed spike ferritin COVID-19 Prevention Network (CoVPN) has phase 1 data, researchers will then study nanoparticle (SpFN), features a multifaced launched a new trial to study the risk of SARS- the vaccine in 250 participants in a phase 2 sphere design that reportedly allows for re- CoV-2 infection and transmission among portion. Approximately one-third of partici- petitive and ordered presentation of the spike college students who have received the pants in the phase 2 study will be between protein to the body’s immune system. Preclini- Moderna COVID-19 vaccine. Researchers will the ages of 60 and 75 years of age. cal research shows that SpFN generates robust evaluate whether the mRNA-1273 vaccine, Novavax has updated its clinical trial and broad neutralizing antibody responses which is authorized for emergency use by protocols for two ongoing clinical trials of against SARS-CoV-2 as well as three variants the FDA, can prevent SARS-CoV-2 infections, NVX-CoV2373, the company’s COVID-19 vac- of the novel coronavirus. A total of 72 healthy reduce viral load in the nose and reduce viral cine candidate. The update allows participants adult volunteers between 18 and 55 years of transmission from vaccinated college stu- from the phase 2b South African trial and the age will be enrolled in the phase 1 study of dents to other people in the community. Re- pivotal phase 3 UK trial to receive additional SpFN. Participants will receive either placebo searchers hope the study will provide greater injection rounds in crossover arms. Study or the investigational vaccine candidate. Copyright © 2021 by WCG CenterWatch CWW2515 CenterWatch Weekly April 12, 2021 4 of 13 Industry Briefs

Gene Therapies for Marks suggested that the four regulators MDIC has 64 members, including John- Neurodegenerative Diseases begin any global harmonization efforts with son & Johnson, Medtronic, Siemens, Philips, May Need Only Phase 1 Trials a focus on ultra-orphan drugs. He and other Danaher and Becton Dickinson. Because of how difficult it is to find top regulators made the comments at last Read the MDIC report here: https://bit.ly/ participants for rare neurodegenerative week’s Alliance for Regenerative Medicines’ 3mtLoIX. disease trials, the FDA says in a recent Meeting on the Med. draft guidance that phase 1 trials of gene Study Finds Pandemic therapies (GT) for such diseases may be Device Consortium Pushes for Mitigation Efforts Impacted sufficient to produce evidence for regula- Stronger Patient Voice in Trials Trial Completion Rates tory submissions. Despite all the hoopla about patient A new study finds that trials sponsored by The agency said eligibility for first-in- engagement, the fact is that the industry is the pharma industry fared better during the human GT trials should, in general, consider still not really engaged. Recent surveys show pandemic and were more likely to complete disease severity or stage as part of the more than 80 percent of industry respon- enrollment compared to trials sponsored by benefit-risk profile and, where feasible, dents never seek patient input as part of academia, hospitals and medical centers. should be initiated in adult patients who protocol development and almost one-third Pandemic mitigation efforts, such as understand the risks and are able to provide estimated they sought such input less than social distancing and lockdowns, caused informed consent. 25 percent of the time. global trial completion rates to decline by The guidance also encourages the use In a 45-page report released last week, 13 percent to 23 percent, depending on of innovative clinical trial designs, such as the Medical Device Innovation Consortium geographic location and who sponsored the adaptive trials, and recommends that trials (MDIC), a partnership of the FDA, NIH and trial, researchers from the Pennsylvania State with a placebo arm should consider giving several pharma heavyweights, presented a College of Medicine found. an already-proven treatment to all partici- roadmap of tactics trials can use to increase The researchers analyzed more than pants before randomizing them. Crossover patient involvement. 117,000 clinical trials worldwide and also trial designs, in which two randomized arms MDIC suggested that when researchers broke out trials conducted in the U.S., alternate treatments to give all participants engage patients about participating in a Europe and Asia. They compared the a chance to receive the investigational prod- trial that they include a discussion about number of clinical trials submitted and uct, also could be used. the applicability of exclusion criteria, on the completed between April and October in Read the FDA’s draft guidance here: grounds that some criteria may be unneces- both 2019 and 2020, using data from the https://bit.ly/3mzyc5x. sarily preventing patients who are otherwise ClinicalTrials.gov database. To more accu- willing to participate. rately assess the impact of the pandemic, Regulators: Focus Global Patients and advocacy groups should researchers analyzed the 2020 dataset Harmonization Efforts be adequately compensated for their both with and without data from trials on Rare Disease Trials participation in a trial, and a transparent related to COVID-19. Regulatory officials from the U.S., UK, EU and communication plan between them and The study found a slight increase in Japan said their agencies should harmonize researchers is essential, MDIC said. It added the overall number of clinical trial submis- rules for clinical trials targeting rare diseases that clinical trial participants or advisers sions between April and October of 2020 because patient populations in some study ar- could continue to play a positive role in compared to 2019, but with COVID-19 eas number only in the hundreds worldwide. supporting interpretation of a study’s related trials removed, there was a 9.7 If enacted, such a strategy could lead to faster findings, and reminded researchers that percent decrease in the number of sub- development of advanced therapy medicinal the process of patient engagement doesn’t mitted trials. Globally, there was a 13.3 products used to treat ultra-rare diseases. end once the patient’s insights have percent decline in the number of clinical Peter Marks, director of the FDA’s Center been recorded and evaluated — it may trials completed in 2020 with COVID-19 for Biologics Evaluation and Research, be necessary, for example, for research- studies included, but that figure grows said there were plenty of diseases with ers to reconcile patient input with input to a 16.7 percent decline without those patient populations so small that it may from other stakeholders, especially if the studies. In the U.S., a 17 percent decline be difficult to field a viable trial in just one feedback from both groups are not aligned in completed trials occurred in 2020 with regulatory jurisdiction. or are in conflict with each other. continues on next page »

COVID-19 studies included; excluded, it and real-world data. The results were that The results were published online by the was a 19.1 percent decline. many common criteria, including exclusions peer-reviewed journal Nature on April 7. Read the report here: https://bit.ly/3w based on several laboratory values, had a Read the report here: https://go.nature. A8O48. minimal effect on trial outcomes. com/3g0rCDM.

AI Study Finds Benefits to Data Point Broadened Eligibility Criteria Clinical Research Site Survey Shows Rapid Shift in Acceptance Researchers said they were able to more of Virtual Solutions than double, on average, the pool of eligible patients in oncology clinical trials by using artificial intelligence (AI) to broaden restric- tive eligibility criteria. In a retrospective study, researchers from Stanford University, in partnership with Genentech, used electronic health records (EHR) of 61,094 patients with advanced nonsmall-cell lung cancer. The data, which came from a nationwide database of highly structured EHRs from Flatiron Health, was then analyzed by Trial Pathfinder, an AI TM framework that uses data-driven algorithms Source: WCG CenterWatch

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This feature highlights changes in clinical marketing and product management at Duke University’s Clinical Trials Transfor- trial organizations’ personnel. Arcis Biotechnology. mation Initiative.

Altis Biosystems Excision BioTherapeutics Overland ADCT BioPharma Bill Thelin has signed on to serve as Altis William Kennedy, former vice president Overland ADCT BioPharma has appointed Biosystems’ new chief scientific officer. Prior of development at Calcilytix, has been Eric Koo to lead the company as its newest to joining Altis, Thelin was vice president of named senior vice president of clinical at CEO. Koo comes to Overland from Takeda research at Parion Sciences. Excision BioTherapeutics. China, where he served as vice president and head of the oncology business unit. Amryt Ichnos Sciences Commercial stage biopharmaceutical com- Cyril Konto has been named chief medical Prothena pany Amryt has named Sheila Frame the officer of biotech company Ichnos Sciences. Late-stage clinical company Prothena has president of Americas. Frame was most re- Prior to this appointment, Konto served as found its newest chief medical officer in cently the vice president and global disease vice president of clinical development at Hideki Garren, former vice president and lead at Novartis Oncology. Allogene Therapeutics. global head of neuroimmunology at F. Hoffmann-La Roche. Arch Oncology IM Therapeutics Laurence Blumberg has been named presi- IM Therapeutics has named David Alleva Rain Therapeutics dent and CEO of Arch Oncology. Blumberg the company’s new vice president of Richard Bryce, former chief medical and comes to Arch from Syntimmune, where he immunology. Alleva previously served as scientific officer of Puma Biotechnology, has served as founding CEO and director. executive director of immunotherapeutics been named executive vice president and at Akston Biosciences. chief medical officer of Rain Therapeutics. Brooklyn ImmunoTherapeutics Howard Federoff will take the helm at ImmuneID Rentschler Biopharma Brooklyn ImmunoTherapeutics as its new- ImmuneID has appointed Annalisa Martin Kessler has been named CEO of est CEO. Previously, Federoff was the CEO D’Andrea to president and chief scientific Rentschler Biopharma’s U.S. subsidiary. of UCI Health. officer. D’Andrea was previously the chief Kessler most recently served as an associate scientific officer of Kiniksa Pharmaceuticals. partner at McKinsey & Co. Cogent Biosciences John Robinson has been named chief sci- Juvenescence Tessera Therapeutics entific officer of Cogent Biosciences’ newly Grazia Piizzi has been named chief David Davidson, former chief medical of- formed Cogent Research Team. Robinson scientific officer of Juvenescence. Formerly, ficer of bluebird bio, has been named chief was most recently the vice president of Piizzi was the senior vice president of small medical and development officer of Tessera medicinal chemistry at Pfizer. molecules R&D and head of inflammation at Therapeutics. Tessera also recently appoint- Cygnal Therapeutics. ed Hari Pujar to chief operating officer and Eloxx Pharmaceuticals Lin Guey to senior vice president of rare dis- Sumit Aggarwal, the former president Lykan Bioscience eases program strategy and operations. Pu- and CEO of Zikani, has been appointed CEO Patrick Lucy, former president and chief jar is the former chief technology officer at of Eloxx Pharmaceuticals. Vijay Modur, operating officer of Lykan Bioscience, has Spark Therapeutics, and Guey most recently another Zikani veteran who served as the been promoted to president and CEO of served as the vice president of program and company’s chief scientific and medical of- the company. portfolio strategy at Xilio Therapeutics. ficer, has been named head of R&D at Eloxx. Medable Tyme Technologies Evonetix Pamela Tenaerts has been hired by Tyme Technologies has named Jan Van Evonetix has appointed Michael Dan- Medable to serve as the company’s chief Tornout as its newest chief medical officer. iels to head of product management. scientific officer. Prior to this appoint- Van Tornout was previously the senior vice Daniels was previously the director of ment, Tenaerts was executive director of president and head of oncology at Natera.

Unnecessary Safety Reports been processing and determined that half of time and money, Beales said. Portals also (continued from page 1) them were not true SUSARs. Consequently, gives sponsors access to various security and of the law by over-distributing and report- Jouravleva said her team reached out to control measures. But he said sites dislike ing every event,” Beales told attendees of sponsors individually and said they would portals for several reasons, particularly that a WCG webinar last week. “That’s not what only process, acknowledge, review and a portal is another proprietary system that the FDA wants, and that noise buries true archive true SUSARs, following the definition a site will need to learn how to use. It also [safety] signals.” outlined in FDA regulations; other reports perpetuates the issue of having a different Sites increasingly are articulating what would not be processed. She also said spon- computer system for every trial. Beales said they will and won’t do as far as safety report- sors were reminded that they — not sites sites also don’t like portals because they feel ing is concerned, passing back to sponsors — are ultimately responsible for the grading they take time away from patient enroll- the responsibility for evaluating whether of safety reports. ment and care, and don’t necessarily see the adverse events are caused by the investiga- “Some [sponsors] are very good at com- direct value in such systems. tional product (IP) and determining which municating and distributing truly relevant Beales co-chairs the Safety Reporting require reporting to regulators and IRBs. information for FDA regulations,” she said. Harmonization Working Group, an inde- Sponsors should notify sites of IP-related “And some of them are just blasting us with pendent group that is voluntarily trying events that are classified as SUSARs, but everything under the sun — even today. to address the safety reporting issue on a too often are flooding sites with multiple The problem is that more is not better. We global scale. He said the group — which in- reports that sites need to process before keep forgetting we distribute this informa- cludes Genentech, Roche, Janssen, Amgen, determining what does and doesn’t qualify tion because a physician’s time is valuable. Covance and WCG — started by making as a SUSAR. They need to be able to [quickly] determine a portal of global laws to ensure sites get Beales said that especially in oncology if there is something applicable to their what they need from sponsors. “We’re not studies, it is difficult to tease out whether an patient’s care or not.” forcing the sites to do anything that is not in event was caused by the IP or the underlying Beales said it takes at least 20 minutes accordance with those laws. It’s all driven by disease. The agency doesn’t want sponsors for a site to process one safety report, and the key spirit of patient safety and protect- to overreact by sending sites multiple follow- Jouravleva said sites are not reimbursed ing the patient. We want to minimize the up reports for the same issue. Doing so could for that extra work. “Maybe that’s some- time that investigators and other people lead to complacency and a feeling at sites thing that needs to be considered at some have to spend away from a patient while that the reports represent something of a point. You just have to do it because they’re making sure all of those valuable safety nuisance, rather than anything actionable. regulations. And when that’s impacting the signals get through.” Elena Jouravleva, director of regulatory budget, then maybe the stringency of the Sponsors have several options at their affairs for the U.S. Oncology Network, a site review is a little bit higher.” disposal to help ease the burden felt by sites, network of about 160 integrated, communi- While Jouravleva said there weren’t any according to Beales. They could send batch ty-based oncology practices, said her team sponsors her network refuses to work with, notifications of safety reports, either on a works with more than 100 sponsors that she advises other sites and site networks daily or weekly basis, and can have a site’s collectively support more than 300 clinical to evaluate whether they want to engage principal investigator (PI) delegate safety trials, and team members log into about in a clinical trial, knowing upfront what the reporting tasks to another member of site 40 different portals on a daily basis to pull administrative or monitoring burdens are staff or a site management organization. safety reports. She said her team was trying going to be. She says her network tells po- Sponsors could also submit a single SUSAR to process between 1,500 and 2,500 safety tential sponsor partners that “these are our about a specific IP to each study involved reports a month during the pandemic, but policies, this is what we are required to pro- instead of blanketing all of the studies’ sites the number has since declined to a range of cess, this is what we will do, this is what we with reports of the same event. between 1,500 and 1,600 safety reports. will not do — because we’re not required Beales said the working group believes After the FDA updated its guidance on to accept anything not clearly indicated as the optimum workflow for sites is a simple safety reporting requirements for investiga- a SUSAR. That’s how we are approaching it, email with any appropriate links inside. tional new drug applications in April 2020, and I highly advise it.” “There is no need for PIs to be signing indi- Jouravleva said her team performed an Sponsors like to communicate with sites vidual SUSARs. The FDA does not want that, assessment of the safety reports they had using portals because they save sponsors and the PIs don’t want that.”

Develop RWD Skills The pandemic helped the agency accurate and representative of the intend- (continued from page 1) crystalize the importance of being able to ed patient population in June 2020, the are being developed so that they can be learn from many different types of data- agency is close to releasing a final version cross-checked by other researchers and also sets, Abernethy said, adding that the FDA’s of its guidance on approaches to identify shared for more general-purpose use.” partnership with the Reagan Udall Foun- what is most important to patients with In developing a framework, Abernethy dation in launching the COVID-19 Evidence respect to their experience as it relates to said the FDA is weighing whether RWD are Accelerator helped to explore how RWD burden of disease and burden of treat- fit for use, whether the clinical trial or study could be put to use. Regulators analyzed ment, which it published in draft form in design used to generate real-world evidence electronic health record systems as well as October 2019. can provide adequate scientific evidence in silico and synthetic datasets. Next up will be two new draft guid- to answer questions by regulators, and In other presentations by FDA officials ances: one on selecting, modifying, de- whether the data and analytic combination last week, Robyn Bent, director of the veloping and validating clinical outcome can satisfy specific regulatory requirements. Patient-Focused Drug Development assessments to measure outcomes of She said the agency was exploring the use of Program at the agency’s Center for Drug importance to patients in clinical trials, RWD for a variety of situations, including as: Evaluation and Research, said the pro- and another on methods, standards and } A supplement to an overarching gram is moving forward on publishing its technologies for collecting and analyz- package to describe an underlying four-guidance series on collecting patient ing clinical outcome assessment data for population; experience data and other relevant infor- regulatory decision-making. Bent says } An information set for secondary indi- mation from patients and caregivers to the agency is almost finished writing and cations or label expansions; and inform drug trial design. Following pub- will be ready to release in draft form. “We } A potential substitute for a control arm lication of the first guidance on methods are working hard to get those out soon,” in a clinical trial. to collect patient experience data that are Bent said.

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Company Drug/Device Medical Condition Status Sponsor Contact COVID-19 Trials and Actions OSE CoVepiT COVID-19 vaccine approval received from the ose-immuno.com Immunotherapeutics Belgian Federal Agency for Medicines and Health Products for phase 1 trial AzurRx Biopharma micronized COVID-19-related gastrointestinal initiation of phase 2 trial azurrx.com niclosamide (FW- infections 1022) The Cancer Research interleukin-7 (IL-7) cancer patients with COVID-19 first patients dosed in phase cancerresearch.org Institute 2 trial

RevImmune revimmune.com Novavax NVX-CoV2373 COVID-19 vaccine initiation of phase 2b and 3 novavax.com trials Abbott BinaxNOW COVID-19 detection of COVID-19 infection Emergency Use Authorization abbott.com Ag Self Test (EUA) granted by the FDA Baebies FINDER 1.5 detection of COVID-19 infection EUA granted by the FDA baebies.com Instrument and FINDER SARS-CoV-2 Test – RT-PCR Quidel QuickVue At-Home detection of COVID-19 infection EUA granted by the FDA quidel.com OTC COVID-19 Test Other Trials and Actions Arcellx ACLX-001 multiple myeloma IND approved by the FDA arcellx.com BioInvent BI-1808 ovarian cancer, nonsmall-cell IND approved by the FDA bioinvent.com International lung cancer and cutaneous T-cell lymphoma Landos Biopharma omilancor (BT-11) eosinophilic esophagitis IND approved by the FDA landosbiopharma.com Tarus Therapeutics TT-10 advanced solid tumors IND approved by the FDA tarustx.com Antengene ATG-019 advanced solid tumors or IND approved by the China antengene.com Corporation (monotherapy or nonHodgkin lymphoma National Medical Products combined with niacin Administration ER) BlueRock MSK-DA01 Cell advanced Parkinson's disease approval received from bluerocktx.com Therapeutics Therapy Health Canada for a phase 1 trial Azafaros AZ-3102 GM1 and GM2 gangliosidoses first cohort dosed in phase azafaros.com 1 trial Celon Pharma CPL’280 diabetes and diabetic neuropathy completion of phase 1 trial celonpharma.com I-Mab TJ-L14B/ABL503 locally advanced or metastatic solid first patient dosed in phase i-mabbiopharma.com tumors 1 trial ABL Biotechnologies ablbio.com Nascent Biotech pritumumab brain cancer, including malignant initiation of phase 1 trial nascentbiotech.com primary brain tumors and adult brain metastases TeneoBio JNJ-75348780 B-cell lymphoid malignancies first patients dosed in phase teneobio.com 1 trial Janssen janssen.com Pinteon Therapeutics PNT001 acute traumatic brain injury first patient dosed in phase pinteon.com 1b trial continues on next page »

Company Drug/Device Medical Condition Status Sponsor Contact SpringWorks nirogacestat nirogacestat in combination with first patient dosed in phase springworkstx.com Therapeutics teclistamab 1b trial Daiichi Sankyo DS-1594 relapsed/refractory acute myeloid initiation of phase 1/2 trial daiichisankyo.com leukemia and acute lymphoblastic leukemia Gracell GC007g B-cell acute lymphoblastic leukemia first patient enrolled in gracellbio.com Biotechnologies phase 1/2 trial Molecular Partners ensovibep patients with symptomatic first patient dosed in phase molecularpartners.com COVID-19 2a trial Recognify Life RL-007 cognitive impairment associated initiation of phase 2a trial atai.life Sciences/atai Life with schizophrenia Sciences AEON Biopharma ABP-450 cervical dystonia first patients dosed in phase aeonbiopharma.com (prabotulinumtoxinA) 2 trial injection Aptinyx NYX-458 patients with mild cognitive restarted patient screening aptinyx.com impairment and mild dementia in phase 2 trial associated with Parkinson’s disease and dementia with Lewy bodies Chinook atrasentan patients with proteinuric glomerular first patient dosed in phase chinooktx.com Therapeutics disease who are at risk of 2 trial progressive loss of renal function Daiichi Sankyo Enhertu (trastuzumab HER2 overexpressing locally first patient dosed in phase daiichisankyo.com deruxtecan) advanced, unresectable or 2 trial AstraZeneca metastatic colorectal cancer with astrazeneca.com progression following treatment with standard-of-care chemotherapy Enzychem EC-18 chemoradiation induced oral patient enrollment complete enzychem.com Lifesciences mucositis in stage 2 of phase 2 trial Kadmon belumosudil diffuse cutaneous systemic sclerosis first patient dosed in phase kadmon.com 2 trial Ocuphire Pharma APX3330 nonproliferative diabetic initiation of phase 2 trial ocuphire.com retinopathy and mild proliferative diabetic retinopathy Ionis ION363 amyotrophic lateral sclerosis with initiation of phase 3 trial ionispharma.com Pharmaceuticals mutations in the fused-in sarcoma gene Relmada REL-1017 adjunctive treatment for major initiation of phase 3 trial relmada.com Therapeutics depressive disorder Da Volterra DAV132 prevention of clostridioides difficile Fast-Track designation davolterra.com infection in high-risk patients granted by the FDA Passage Bio PBKR03 Krabbe disease Orphan Drug designation passagebio.com granted by the European Commission Taiho Oncology futibatinib (TAS-120) treatment of patients with Breakthrough Therapy taihooncology.com previously treated locally advanced designation granted by the or metastatic cholangiocarcinoma FDA harboring FGFR2 gene rearrangements, including gene fusions continues on next page »

Company Drug/Device Medical Condition Status Sponsor Contact Sanofi Sarclisa (isatuximab) treatment of patients with relapsed approved by the FDA for sanofi.com in combination with refractory multiple myeloma who expanded indication carfilzomib and have received one to three prior dexamethasone lines of therapy Supernus Qelbree (viloxazine attention deficit hyperactivity approved by the FDA supernus.com Pharmaceuticals extended-release disorder in pediatric patients 6 to 17 capsules) years of age United Therapeutics Tyvaso (treprostinil) pulmonary hypertension associated approved by the FDA unither.com Inhalation Solution with interstitial lung disease Bausch and Lomb ClearVisc dispersive ophthalmic surgery approved by the FDA bauschhealth.com ophthalmic viscosurgical device Chemence Medical Exofin fusion skin topical adhesive to close and seal approved by the FDA chemencemedical.com closure system incisions NuVasive NuVasive Simplify two-level cervical total disc approved by the FDA nuvasive.com Cervical Artificial Disc replacement Respinova Pulsehaler inhaler for patients with respiratory approved by the FDA respinova.com diseases Vysioneer VBrain, AI- radiotherapy treatment approved by the FDA vysioneer.com powered tumor autocontouring solution

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Research Center Spotlight is a selection of clinical research centers who have Research Center Profile pages posted on CenterWatch.com. Included in their annual subscriptions, company profiles are randomly selected to appear in this section, providing added exposure for their expertise and services in conducting and managing clinical studies. To learn more about becoming a Research Center Profile page subscriber, contact Sales at 617.948.5100 or [email protected].

Advanced Dermatology Institute IMIC Torrance, CA Palmetto Bay, FL 310.378.8885 786.310.7477 [email protected] [email protected]

The Advanced Dermatology Institute is a dermatology and surgical The center was established in 2012 as a continuation of successful cosmetic physician practice. completion of more than 63 trials in previous research clinics.

Alea Research Institute J. Lewis Research Phoenix, AZ Salt Lake City, UT 602.562.7000 801.487.2072 [email protected] [email protected]

Alea Research is a full-time dedicated research center focusing on J. Lewis is a unique research company with more psychiatric and central nervous system clinical trials. than 28 years of experience conducting clinical trials for the pharmaceutical industry, specializing in phase 2 to 4 trials. HealthPark Medical Center Long Beach Clinical Trials Fort Myers, FL Long Beach, CA 239.343.5506 562.436.4761 [email protected] [email protected]

Located within HealthPark Medical Center, Shipley Cardiothoracic Long Beach Clinical Trials is a leading research site dedicated to Center provides a contemporary approach to the surgical treatment improving health and wellness by conducting phase 1 to 4 research of the heart and lungs. studies.

Health Concepts Manhattan Medical Research Rapid City, SD New York, NY 605.348.4141 212.480.3333 [email protected] [email protected]

Health Concepts is a state-of-the-art research center built in 2009 Manhattan Medical Research is a multispecialty medical research site with complete technology for a wide range of research studies. proficient in phase 2 through 4 clinical trials.

300 N. Washington St., Suite 200 • Falls Church, VA 22046-3431 Phone: 866.219.3440 or 617.948.5100 www.centerwatch.com Customer Service: [email protected] Editorial Director: Beth Belton, 703.538.7641, [email protected] Reporter: Charlie Passut, 703.538.7664, [email protected] Sales: Russ Titsch, 813.767.6463, [email protected] Copyright © 2021 by WCG CenterWatch. All rights reserved. CenterWatch Weekly (ISSN 1528-5731), an executive news briefing for the clinical trials industry, is published 48 times a year and is available for free. Photocopying or reproducing in any form is a violation of federal copyright law and is strictly prohibited without the publisher’s permission.