US clinical trial sites are most affected due to the Covid-19 pandemic

With the recent development of the current Covid-19 pandemic, there has been an increased urgency for both industry and non-industry sponsors to focus on finding a suitable therapeutic or vaccine for this highly contagious viral disease. In an effort to find a suitable treatment and prevention options for Covid-19 infection, more Covid-19 clinical trials are being planned and initiated, while a large number of clinical trials for non-Covid-19 indications are suffering delays.

With many regulatory agencies such as the FDA and EMA offering accelerated approval for Covid-19 therapeutics and vaccines, it could be in part that sponsors have shifted focus and research onto the current pandemic. But the majority of trial disruption could be attributed to patient safety, strict lockdown, social distancing, and the high demand for medical professionals to treat Covid-19 patients. High profile pharmaceutical companies have announced disruptions to planned and ongoing trials, postponing trial start dates and halting subject enrolment.

The Covid-19 Dashboard on the Pharma Intelligence Center dynamically tracks these disrupted trials from the Clinical Trials Database, along with the list of companies that are the sponsor, collaborator, or contract research organisation (CRO).

With over 1,000 trials being disrupted and more trials being added to this category daily, there is a direct impact on trial site activation and patient enrollment. Many of these sites are either being used for other purposes or are temporarily closed. With many countries enforcing strict lockdown measures, sponsors are unable to activate these sites, making it harder for existing trials to continue. According to GlobalData’s Clinical Trials Database, 56.1 % of disrupted trials are currently suspended while 20.7% are ongoing, but not recruiting any additional participants. When looking at site locations, the US had the highest number of disrupted trial sites at 66.1% followed by the UK at 12.8%, France at 9.3%, Spain at 6.5%, and Germany at 5.2%, as shown in Figure 1. According to the guidance of FDA and EMA procedures, many of these disrupted trial sites are now being repurposed for Covid-19 trials. Activation of new trial sites is usually not recommended for non-Covid-19-related trials unless no other solution exists for the ongoing trials. According to the EMA, “If there is an urgent need to open a new trial site for critical trial visits, for example outside the hospital, this may be implemented as an urgent safety measure (USM) first, followed later by a substantial amendment (SA) application for the approval and initiation of this additional site.” With the possibility of reallocating trial sites, there is also the need to move subject data such as medical records. In such cases, it is highly recommended from the EMA that this is done virtually and that any eCRFs can be adjusted accordingly to allow the receiving site to enter new data.

Due to site closures and lockdown measures, many companies involved in trial site management and coordination are feeling an economic hit. The top three countries with affected companies are the US, UK, and France. Contract research organisations are experiencing a hit too, with many organisations having to disrupt trials. According to GlobalData’s Clinical Trials Database, the top three CROs that are affected are IQVIA, Covance, and Sarah Cannon Research Institute. Among CROs, a statement from ICON highlights that 65% of their global sites are impacted in some way, which poses a period of financial uncertainty. Many companies are reviewing alternative approaches by using remote measures and virtual clinical trials, which aim to bring the study directly to the patient via online data collection and video call progress checks. It is important to note that with many countries easing lockdown, some trial sites may begin to reopen slowly to focus on other studies. With many companies shifting to alternative ways to conduct trials, it is possible that even after the Covid-19 pandemic the use of virtual trials will remain prominent.

Source: Clinical Trials Arena

Commonly used steroid reduces risk of death in sickest coronavirus patients, preliminary study results suggest

(CNN) – The widely available steroid drug dexamethasone may be key in helping to treat the sickest Covid-19 patients who require ventilation or oxygen, according to researchers in the United Kingdom.Their findings are preliminary, still being compiled and have not been published in a peer-reviewed journal — but some not involved with the study called the results a breakthrough.

The two lead investigators of the Recovery Trial, a large UK-based trial investigating potential Covid-19 treatments, announced to reporters in a virtual press conference on Tuesday that a low-dose regimen of dexamethasone for 10 days was found to reduce the risk of death by a third among hospitalized patients requiring ventilation in the trial.

“That’s a highly statistically significant result,” Martin Landray, deputy chief investigator of the trial and a professor at the University of Oxford, said on Tuesday.

“This is a completely compelling result. If one looks at the patients who did not require ventilators but were on oxygen, there was also a significant risk reduction of about one-fifth,” Landray said. “However, we didn’t see any benefit in those patients who were in hospital, had Covid, but whose lungs were working sufficiently well — they were not taking either oxygen or on ventilators.”

Landray added that “there are outstanding questions” and people treating Covid-19 at home should not be taking dexamethasone on the back of these results.

“We have not studied patients in the community,” Landray said. “We show no effect in the patients who are not on oxygen and we did not study the patients who are not in hospital.

“The dexamethasone arm of the Recovery Trial closed last week and researchers are now compiling its data. It included about 2,100 hospitalized Covid-19 patients who were randomized to receive dexamethasone, and about 4,300 hospitalized Covid-19 patients who were randomized to receive the usual standard of care at their hospitals.

In the trial, dexamethasone was provided at a dose of 6mg once a day for up to 10 days, administered either as an injection or taken orally. The researchers reported no serious adverse events among the patients taking dexamethasone, but the results are preliminary.

“At this stage, we found no clear adverse effects of doing this. Let’s recognize that there are sort of two messages here. In the people who required oxygen or ventilation, it clearly works, and the benefits are biggest for those on ventilators. In the people in hospital with Covid who do not require oxygen — so, their lungs are working moderately well — then actually there’s no benefit,” Landray said on Tuesday.”

In the trial, our focus was on mortality, which obviously a drug can affect in either direction, but the overall results in the patients on oxygen and ventilation was a clear, clear benefit,” Landray said, adding that deaths in the study were examined over a 28-day period. “We’ve looked, for example, were there deaths due to other forms of infection, which are sometimes considered a risk? And the answer is no, there was no excess of any other particular cause of death.”

Dexamethasone is typically used to treat certain forms of arthritis, severe allergies and asthma, among other conditions, including certain types of cancer. Side effects can include upset stomach, headache, dizziness, insomnia and depression. GoodRx estimates the drug can cost as low as about $8.

In the United States, dexamethasone already has been used to treat some Covid-19 patients during the pandemic.

When told about the preliminary Recovery Trial results, Dr. Mangala Narasimhan, the regional director for critical care at Northwell Health, which owns 23 hospitals in New York, said to CNN, “We’ve used it for Covid from the beginning.”

Dexamethasone has been a controversial drug when it comes to treating respiratory viral infections, Peter Horby, chief investigator for the Recovery Trial and a professor at the University of Oxford, said on Tuesday.

“This was included in the Recovery Trial because it’s a readily available, cheap and well understood drug, and because there have been reports in the past of benefit in viral respiratory infections, but it’s been an area of huge controversy,” Horby said.

“Even at the time of SARS1 in 2003, steroids were used, but at very different doses. Some of the studies showed a harm from steroids in SARS, some said there’s possible benefits. A meta-analysis in 29 different studies in SARS was inconclusive. There’s also been inconclusive results on MERS coronavirus and also influenza,” Horby said. “So really it’s been a huge ongoing debate as to whether you should use steroids in patients with viral respiratory diseases.

“The researchers said on Tuesday that they think this now should become a standard of care in the United Kingdom for Covid-19 patients requiring either oxygen or ventilation — but in the meantime, the Recovery Trial continues to investigate other treatment approaches.

“This is tremendous news today from the Recovery trial showing that dexamethasone is the first drug to reduce mortality from COVID-19. It is particularly exciting as this is an inexpensive widely available medicine,” Sir Patrick Vallance, the UK Government’s chief scientific adviser, said in a news release from the Recovery Trial team on Tuesday.

“This is a ground-breaking development in our fight against the disease, and the speed at which researchers have progressed finding an effective treatment is truly remarkable,” Vallance said. “It shows the importance of doing high quality clinical trials and basing decisions on the results of those trials.”

Nick Cammack, the Covid-19 Therapeutics Accelerator lead at Wellcome Trust in the UK, said in a written statement on Tuesday that the dexamethasone findings are a “major breakthrough.”

“This is a major breakthrough: dexamethasone is the first and only drug that has made a significant difference to patient mortality for COVID-19. Potentially preventing 1 death in every 8 ventilated patients would be remarkable,” Cammack said in the statement.

“Finding effective treatments like this will transform the impact of the COVID-19 pandemic on lives and economies across the world. While this study suggests dexamethasone only benefits severe cases, countless lives will be saved globally,” Cammack said in part. “Dexamethasone must now be rolled out and accessed by thousands of critically ill patients around the world. It is highly affordable, easy to make, can be scaled up quickly and only needs a small dosage.”

Now researchers and physicians around the world are calling for the Recovery Trial team to release its data on dexamethasone as a potential treatment for severe Covid-19.

“The Oxford group’s important results, based on a scientific trial in over 6000 NHS patients, show that dexamethasone — a common, widely used, inexpensive medicine — can save lives in seriously ill patients with COVID-19,” Robin Ferner, honorary professor of clinical pharmacology at the University of Birmingham and honorary consultant physician at the City Hospital Birmingham in England, said in a statement released by the UK-based Science Media Centre on Tuesday.

“It is not a treatment for mild disease,” he said. “We hope the data on which these results are based will be published as soon as possible so that doctors can confidently put the treatment into practice.”

Source: CNN

Johnson & Johnson is moving its coronavirus vaccine into human trials by July, 2 months ahead of schedule

Johnson & Johnson said Wednesday it plans to start human testing of its coronavirus vaccine candidate in July. 

Previously, J&J had said the goal was to enter human trials in September. J&J is the world’s largest healthcare company with a market value of $390 billion. The company has previously pledged to distribute its vaccine on a not-for-profit basis for emergency pandemic use. 

Paul Stoffels, the company’s chief scientific officer, said in a news release Wednesday that the accelerated pace stemmed from “the strength” of preclinical data and conversations with regulators.

The study will start in the second half of July and enroll 1,045 healthy volunteers in the US and Belgium. The initial study will have a placebo arm to compare results against. Researchers will look to see how safe and tolerable the vaccine is when injected in humans, and if it causes an immune response.

It won’t be the only trial for J&J’s vaccine. The company said it is talking with the US National Institutes of Health to start a larger, late-stage study “ahead of its original schedule.” J&J executives have previously said they expect the vaccine to be ready by early 2021 for emergency use.

J&J’s program is one of more than 125 ongoing vaccine research programs. Ten are now in human testing, and more than 25 are expected to enter the clinic by year’s end.

Source: Business Insider

Out of the lab and into people’s arms: A list of COVID-19 vaccines that are being studied in clinical trials

The world’s leading drug companies, universities and governments are racing to develop a vaccine for COVID-19, the disease that has taken more than 400,000 lives globally. Of the 133 candidates being explored, ten have been approved for human trials, according to the World Health Organization.

Companies and research groups in China, the early epicenter of the coronavirus outbreak, are testing five of those vaccines in human trials.

Meanwhile, U.S.-based companies are involved in the development of four additional vaccines, including one that has NIAID Director Anthony Fauci “cautiously optimistic.” The Trump administration established a federal program to make 300 million doses of a successful vaccine available to Americans by January 2021.

Some scientists are testing tried-and-true methods, while others are embracing new technologies like DNA- and RNA-based platforms. The goal is to create a safe, effective vaccine that is easy to replicate — at record speed.

Governments have provided billions in funding to researchers who are accelerating the traditional stepwise approach that includes phases 1, 2 and 3. And many entrants have already partnered with manufacturing companies to start scaling up production before they even know if their vaccine will work.

These accelerated efforts to thwart the pandemic have some officials, including Dr. Fauci, hopeful that a vaccine will be ready by year’s end. But if the vaccines currently in human trials fail — which is possible — that timeline will be extended.

Here are the companies leading the global race for a coronavirus vaccine. There are no approved vaccines or treatments for COVID-19 to date, and we still need more data to know if any of these vaccines will prove safe and effective.

AZD1222, The University of Oxford and AstraZeneca (Phase 2/3)

Perhaps one of the fastest-moving projects is Oxford’s, which is enrolling 10,260 people across the U.K. to begin phase 2/3 human trials. Their AZD1222 vaccine, formerly known as ChAdOx1 nCoV-19, uses a weakened version of a virus derived from chimpanzees. Oxford’s partner, AstraZeneca, has already promised enough manufacturing capacity to produce at least 2 billion doses of AZD1222.

mRNA-1273, Moderna Therapeutics and the National Institute of Allergy and Infectious Diseases (NIAID) (Phase 2)

This vaccine uses a new type of technology called messenger RNA, which produces genetic instructions that direct cells to make proteins that prevent disease. Early data from Moderna’s first clinical trial show the mRNA vaccine triggered an immune response similar to patients who have recovered from COVID-19. The Massachusetts-based company is quickly moving on to larger human trials as it aims to complete its vaccine trials by year’s end.

Ad5-nCoV, CanSino Biological Inc. and the Beijing Institute of Biotechnology (Phase 2)

CanSino Biologics, a Chinese vaccine company, is creating a viral vector vaccine that combines a weakened virus called adenovirus type 5 with genetic material from SARS-CoV-2. Early results from CanSino’s phase 1 study, which tests for safety, showed the vaccine produced an immune response against the virus and participants tolerated it well. CanSino is collaborating with Canada’s National Research Council to begin research in Canada.

BNT162, Pfizer, Fosun Pharma and BioNTech (Phase 1/2)

Pfizer and BioNTech started dosing the first participants with their vaccine candidate in Berlin in late April. Soon after, the companies began testing four versions of its mRNA-based vaccine at New York University, the University of Maryland, Cincinnati Children’s Hospital Medical Center and the University of Rochester, in May. The companies will narrow down the candidates by safety and how well they prevent infection in patients. Pfizer CEO Albert Bourla said the vaccine could be ready by the end of October.

NVX-CoV2373, Novavax (Phase 1/2)

The Department of Defense recently awarded Novavax $60 million for the manufacture of this protein-based vaccine, which uses patented nanoparticle technology to enhance immune response. In animal studies, it stimulated high levels of antibodies that neutralized the virus. Phase 1 trials are taking place in Herston and Melbourne, Australia. Novavax expects preliminary results in July and, if successful, the company will move onto larger clinical trials in multiple countries.

CoronaVac, Sinovac Biotech (Phase 1/2)

CoronaVac is an inactivated vaccine being tested in China. This type of vaccine uses a killed version of the germ that causes the disease to stimulate an immune response, and has been used to prevent hepatitis A, polio, rabies and the flu. Sinovac published a study in May that showed its vaccine protected monkeys against infection. The company is currently testing 144 people in phase 2 trials.

Unnamed vaccines, Sinopharm (Phase 1/2)

Sinopharm, a state-run Chinese pharmaceutical company, is developing two inactivated vaccines at their subsidiaries, the Wuhan and Beijing Institutes of Biological Products. Both have entered Phase 1/2 testing, according to the WHO.

INO-4800, Inovio Pharmaceuticals (Phase 1)

INO-4800 is a DNA-based vaccine targeting the spike surface protein of SARS-CoV-2 virus that causes COVID-19. Researchers administer the vaccine by skin injection, then follow with Inovio’s CELLECTRA smart device. This delivers DNA to cells using a pulse of electricity that temporarily opens pores in the cell membranes. Early data from preclinical studies shows the vaccine produced a strong immune response in mice and guinea pigs. Phase 1 study is taking place at Central Kentucky Research Associates, the Center for Pharmaceutical Research in Kansas City, Missouri, and the University of Pennsylvania.

Unnamed vaccine, Institute of Medical Biology, Chinese Academy of Medical Sciences (Phase 1)

The Institute of Medical Biology at the Chinese Academy of Medical Sciences (IMBCAMS) has previously developed the world’s first inactivated vaccines for polio and hand-foot-and-mouth disease, according to the company website. This inactivated vaccine is in phase 1 trials for safety, according to the WHO.

Source: ABC News

Gilead Announces Results From Phase 3 Trial of Remdesivir in Patients With Moderate COVID-19

Gilead Sciences, Inc. (Nasdaq: GILD) today announced topline results from the Phase 3 SIMPLE trial in hospitalized patients with moderate COVID-19 pneumonia. This open-label study evaluated 5-day and 10-day courses of the investigational antiviral remdesivir plus standard of care, versus standard of care alone. The study demonstrated that patients in the 5-day remdesivir treatment group were 65 percent more likely to have clinical improvement at Day 11 compared with those in the standard of care group (OR 1.65 [95% CI 1.09-2.48]; p=0.017). The odds of improvement in clinical status with the 10-day treatment course of remdesivir versus standard of care were also favorable, trending toward but not reaching statistical significance (OR 1.31 [95% CI 0.88-1.95]; p=0.18). No new safety signals were identified with remdesivir across either treatment group. Gilead plans to submit the full data for publication in a peer-reviewed journal in the coming weeks.

“Our understanding of the spectrum of SARS-CoV-2 infection severity and presentations of COVID-19 continues to evolve,” said Francisco Marty, MD, an infectious diseases physician at Brigham and Women’s Hospital, and associate professor of medicine at Harvard Medical School. “These study results offer additional encouraging data for remdesivir, showing that if we can intervene earlier in the disease process with a 5-day treatment course, we can significantly improve clinical outcomes for these patients.”

Remdesivir is currently approved in Japan as a treatment for patients infected with SARS-CoV-2, the virus that causes COVID-19. Outside of Japan, remdesivir is an investigational, unapproved drug. The U.S. Food and Drug Administration (FDA) granted remdesivir an Emergency Use Authorization for the treatment of hospitalized patients with severe COVID-19; the authorization is temporary and does not take the place of the formal new drug application submission, review and approval process.

In this study, hospitalized patients with confirmed COVID-19 infection and evidence of pneumonia without reduced oxygen levels were randomized (1:1:1) to receive open-label remdesivir for 5 or 10 days or standard of care alone. The primary endpoint was the clinical status as assessed by a 7-point ordinal score at Day 11, ranging from hospital discharge to increasing levels of oxygen and ventilatory support to death. The secondary study objective was the rate of adverse events in each remdesivir treatment group compared with standard of care.

At Day 11, a higher proportion of patients in the 5-day treatment group achieved improvement in clinical status versus the standard of care group, achieving statistical significance for a ≥ 1-point improvement in ordinal scale (p=0.026). In addition, non-statistically significant increases in clinical worsening or death were observed in the standard of care only group compared with the remdesivir groups.

“We now have three randomized, controlled clinical trials demonstrating that remdesivir improved clinical outcomes by several different measures. Today’s results showed that when treating moderate disease, a 5-day course of remdesivir led to greater clinical improvement than standard of care, adding further evidence of remdesivir’s benefit to previously released study results. The National Institute of Allergy and Infectious Diseases’ placebo-controlled study showed that remdesivir enabled more rapid recovery and that earlier treatment improved clinical outcomes. Our SIMPLE-Severe study showed that when treating patients with severe disease, 5 days of remdesivir led to similar clinical improvements as a 10-day course,” said Merdad Parsey, MD, PhD, Chief Medical Officer, Gilead Sciences. “The additional data we have in hand today will further guide our research efforts, including evaluating treatment earlier in the course of disease, combination studies with other therapies for the most critically ill patients, pediatric studies and the development of alternate formulations.”

Remdesivir was generally well-tolerated in both the 5-day and 10-day treatment groups. The most common adverse events occurring in more than 5 percent of patients in both treatment groups were nausea (5-day: 10% / 10-day: 9% / SOC: 3%), diarrhea (5-day: 5% / 10-day: 5% / SOC: 7%) and headache (5-day: 5% / 10-day: 5% / SOC: 3%).

Key efficacy and safety results from the study are included in the table below.

 5-Day RDV
n=191
10-Day RDV
n=193
SOC
n=200
Clinical Efficacy Outcomes at Day 11
≥ 2-point improvement in ordinal scale134 (70)126 (65)121 (61)
≥ 1-point improvement in ordinal scale146 (76)135 (70)132 (66)
Requiring any oxygen support12 (6)13 (7)22 (11)
≥ 1-point worsening in ordinal scale6 (3)12 (6)22 (11)
Death02 (1)4 (2)
Safety
Any adverse event (AE)97 (51)106 (55)90 (45)
Grade ≥3 AE20 (10)21 (11)24 (12)
Any serious adverse event (SAE)8 (4)7 (4)18 (9)

About the SIMPLE Trials

Gilead initiated two randomized, open-label, multi-center Phase 3 clinical trials for remdesivir, the SIMPLE studies, in countries with a high prevalence of COVID-19 infections. The studies were conducted at more than 180 trial sites around the world, including sites in the United States, China, France, Germany, Hong Kong, Italy, Japan, Korea, the Netherlands, Singapore, Spain, Sweden, Switzerland, Taiwan and the United Kingdom.

The first SIMPLE trial is evaluating the safety and efficacy of 5-day and 10-day dosing durations of remdesivir administered intravenously in hospitalized patients with severe manifestations of COVID-19. The initial phase of the study randomized 397 patients in a 1:1 ratio to receive either a 5-day or a 10-day treatment course of remdesivir in addition to standard of care. Topline results were announced on April 29 and the full data were published in The New England Journal of Medicine on May 27. An expansion phase of the study was added to enroll up to 5,600 additional patients, including those on mechanical ventilation.

The second SIMPLE trial is evaluating the safety and efficacy of 5-day and 10-day dosing durations of remdesivir administered intravenously in hospitalized patients with moderate manifestations of COVID-19, compared with standard of care. The initial phase of the study randomized 600 patients in a 1:1:1 ratio to receive either a 5-day or a 10-day treatment course of remdesivir in addition to standard of care, compared with standard of care alone. An expansion phase of the study was added to enroll up to 1,000 additional patients with moderate disease. The initial study results are announced in this press release, and results from the expansion phase are expected in the coming months.

Source: Gilead

Vanda Pharmaceuticals CEO’s Proposal on Clinical Trial Data Sharing, COVID-19 and Remdesivir

Mihael H. Polymeropoulos, M.D., President and CEO of Vanda Pharmaceuticals

The COVID-19 pandemic has created an urgent need for scientific solutions to this deadly virus. The pandemic surprised the world with a new strain of coronavirus never encountered before, which, like its predecessor, has the capacity to infect humans with severe and deadly consequences. While this pandemic has stunned the world’s populations, we are more prepared than ever to respond with a rich scientific armamentarium of tools that can be deployed in the war against this new virus resulting from the extraordinary advances in medical discoveries and treatments in the twenty years since the first full sequencing of the human genome.

While the reaction to the 1918 world epidemic was mostly one of quarantine and restrictions in movement, the world today can do better. In 1918, the world did not know the identity of the organism that was killing so many, nor did it know what a virus was, as viruses had not yet been discovered. Now equipped with the knowledge of over a century of research and tremendous advances in science and therapeutics, we stand in front of this challenge well equipped and ready to respond. In many ways, our response has been similar to the 1918 epidemic, with mitigation measures that include closing of public places and reducing opportunities for contact, while monitoring the curves of new cases and mortality rates. Vaccines and therapeutics are on the drawing board but how and when they may be of value is uncertain. The urgency and mobilization of the scientific community across the globe is impressive. The collective scientific understanding of the workings of the virus, the clinical course of the infection and the therapeutic approaches are mounting on a daily basis.

Although this is great news, the pandemic has imposed an extremely demanding pace on the timetable for the pursuit of scientific answers and solutions. The ability of developing therapeutic solutions does not just depend on the availability of research tools and ideas. The ideas must leverage scientific tools and then they must be tested. Testing of potential therapeutics happens in human volunteers that have been infected with the COVID-19 virus. One of these programs is the development of antivirals that are intended to slow down or block replication of the virus.

The U.S. National Institute for Allergy and Infectious Diseases (NIAID) and Gilead Sciences brought forward the testing of one of these antivirals, remdesivir, a nucleoside analog that induces errors in the copying machinery of the virus, thereby slowing down replication. Remdesivir has been recently studied in two types of programs, a placebo-controlled study and an open label program. The NIAID remdesivir placebo-controlled study was concluded and topline results were reported on April 29, 2020. The topline results were communicated during a brief meeting at the White House by the Director of NIAID and advisor to the President, Dr. Anthony Fauci. The communication was verbal, short, and conveyed that the study had shown that remdesivir reduced hospital stay by 4 days for remdesivir treated patients as compared to placebo, but it did not significantly reduce mortality. No other data were presented in any other scientific or media forum. Dr. Fauci acknowledged that his preference would have been to present this data at a scientific meeting but that the situation required a more immediate communication and that the data would be submitted for a peer review publication in the near future. Two days later, the U.S. Food and Drug Administration (FDA) issued an Emergency Use Authorization (EUA) approval of remdesivir in treating patients with severe COVID-19 infection.1 The prescribing information presented by the FDA included the same summary information that was reported at the White House two days earlier, but no additional information on the efficacy trial was given.2 Similarly, the FDA in its cover letter suggested that it had reviewed the topline data and based on that deemed it appropriate to issue an EUA.

The paucity of information around this critical therapeutic development for COVID-19 is troubling. The NIH, the FDA and Gilead Sciences could simply provide the raw data from the clinical trials to the public immediately. Such a concept of sharing of clinical trial data is not new, instead, it is highly encouraged by the scientific community and data sharing disclosures are now required by most scientific journals according to the recommendations of the International Committee of Medical Journal Editors. 3 The reason for sharing of clinical data includes allowing the scientific community to independently form their own conclusions from their own analyses, develop new insights from the data, and accelerate discoveries in the field by not having to repeat the same experiments. In the case of remdesivir and COVID-19, this degree of data sharing is even more urgent given the finite amount of time within which a study can be conducted in the face of a declining number of new cases. There are a number of questions that could be answered by the existing remdesivir NIAID study that remain unanswered by the complete unavailability of the data. For example: Is there a subgroup of patients that performed better than others? Is this subgroup of a certain characteristic, such as age, sex, race, genetic makeup, time since infection, severity of disease, viral load, medication, underlying condition? And there are many others to be answered.

The FDA has authorized remdesivir for all people with severe COVID-19 infection, but there may not be enough supply for all eligible patients at this time. How are doctors supposed to choose who should receive it? The prevailing rationale, which would suggest that it be administered to the most severely ill first, may be misguided and not supported by the data. What if analysis of the existing data showed that remdesivir works better when given to less severe patients or very early after the infection? In this example, providing the currently limited supply of remdesivir to severe patients may be wasteful and may deprive patients who could benefit from it instead. Another reason for sharing the raw data is that there is no other large dataset of patients with COVID-19 infection and thus there is not a good guide how to optimally design any therapeutic programs. The question of whether viral load is associated with response is also of critical importance. Imagine a scenario where the drug’s effect was dependent not on disease severity but rather on viral load, so that severely ill patients with low viral load respond to the drug, but severely ill patients with high viral load do not. What if some patients have zero viral load but nonetheless have a severe infection, would they be candidates for treatment? Even in a more complex scenario, what if patients had no decrease in viral load but the infectivity of the virus post remdesivir treatment was decreased? What is the cause of mortality and how does it differ between remdesivir and placebo?

Unfortunately, so far there has been little to no discussion about data transparency and data availability for remdesivir. Dr. Fauci’s statement that the results will be submitted for peer review is not enough. On the face of it, it appears that this is consistent with the well-established approach to validate scientific findings. During this process, a scientific report is submitted to a journal and the editorial board appoints two or more reviewers to independently critique the paper and advise whether the conclusions are supported by the data presented. This process is well-intentioned, and has served us well, but in and of itself it is grossly inadequate for the task in hand. The American public is comforted that expert scientists opine on the validity of a potential treatment but they would likely prefer that the data are also fully and transparently available to the public for inspection and analysis for both verifying and learning.

Reliance upon just the ordinary peer review of scientific reports is not sufficient in this case. Dr. Fauci’s suggestion that worries about “leaks” or “ethical concerns” prompted this style of announcement is not an acceptable explanation either. Most of the American public is not concerned with the reasons that compelled the verbal announcement of the results from a White House office on April 29. The American public is interested in seeing the data and having the data available for all to examine and learn from. The speed of the FDA decision in issuing an EUA for remdesivir needs to be commended but the absence of any available detailed information is of great concern. The EUA was granted based on the information presented to the FDA. The data which the FDA used to make its decision must become immediately available to the public. If the FDA deems that it needs more information to grant a full approval, it can request this information in due course. Until then, the FDA should provide to the public the information that the FDA scientists used to make its decision.

If the NIAID, the FDA and Gilead Sciences decided to follow this recommendation and share the data, could they do it quickly? The process that the NIAID scientists used to analyze the available data is as follows: anonymized patient data are collected throughout the study, they are tabulated as raw data, and then certain parameters are derived. These data are stored in standard format files which are of two types, the RAW and the DERIVED data files. These exact files that the NIAID analyzed and which Gilead Sciences filed with the FDA, can be shared with minimal effort and within minutes after the leaders of the NIAID, the FDA and Gilead Sciences decide to share. In summary, there is no technical hurdle for the immediate release of the underlying remdesivir clinical study data. Concerns about credit and intellectual property can easily and expediently be addressed without imposing any delay on the release of this data.

We are experiencing a historic health crisis where success is dependent on a community coming together and overcoming a tremendous challenge to humanity. Open source sharing of information has always accelerated solutions to problems, and I am confident that it will work here as well. In the scientific community, open source mentality and data sharing has served humanity well, especially recently with the Human Genome project, where genetic data were made immediately available to the scientific community for the betterment of human health. This is the time to show that pharmaceutical companies and government agencies put patients first. If indeed the interest of patients is front and center, which it should be, then the NIAID, Gilead Sciences and the FDA will release ALL data from the remdesivir studies without delay.

More than ever, the American public is dependent on the competencies of its leaders, in the government and science alike. Trust in the system is conditional and temporary and is based upon transparency and truthfulness. The American public will not, and should not, blindly trust the expert. The American public should not have to wait for a handful of scientists, no matter how brilliant, to review the information and give their approval. The American public is entitled to unconditional access to all such data so that all people, and not just a few, can judge the course of affairs and make decisions. In the midst of this difficult moment for humanity, an unconditional data sharing movement may become a silver lining and the rainbow promise past the storm. The American public, scientists, and non-scientists, bonded by sharing and trust, will overcome this new challenge. Let us remove from the vocabulary of our democracy the “trust me I am an expert” mentality and replace it with “transparency for all.”

Source: Vanda Pharmaceuticals

Merck in collaboration to develop coronavirus vaccine, with clinical trials to start this year

U.S. drugmaker Merck on Tuesday said it plans to work alongside nonprofit scientific research organization IAVI to develop a potential vaccine against the coronavirus.

The news helped send Merck shares up about 3% during the premarket.

The announcement comes as drugmakers pause other clinical trials and scramble to find an antidote for Covid-19, which has infected more than 5.5 million people worldwide and killed over 346,000.

Most experts agree could take 12 to 18 months to roll out a safe vaccine to the market. And, even if an effective vaccine becomes available, many have warned of significant logistical challenges around distributing enough doses for the global population.

In a statement, Merck and IAVI said their vaccine candidate would use the recombinant vesicular stomatitis virus technology that is the basis for its Ebola Zaire virus vaccine — which was the first rVSV vaccine approved for use in humans.

Ebola Zaire is one of six known species within the genus Ebola virus, an acute deadly illness. The virus causing the current outbreak in the Democratic Republic of Congo, and the 2014 to 2016 West African outbreak, belongs to the Ebola Zaire virus species, according to the World Health Organization.

Designed and engineered by IAVI scientists in New York, the vaccine candidate for Covid-19 is in preclinical development. Clinical studies are expected to start this year.

If approved, Merck said both organizations would work together to develop the vaccine and “make it accessible and affordable” worldwide.

Last month, WHO Director General Dr. Tedros Adhanom Ghebreyesus said it was important that, when a vaccine is ready, it could be equitably distributed across the globe.

“There should not be a divide between the haves and the have-nots,” he stressed.

‘Operation Warp Speed’

President Donald Trump has voiced ambitions for a vaccine to be developed and distributed by the end of 2020, in a project called “Operation Warp Speed.”

However, medical experts — including Dr. Anthony Fauci, the U.S. government’s top infectious disease expert — have cast doubt on Trump’s goal, expressing skepticism over the time frame.

Dr. Mark Feinberg, IAVI president and CEO, said the rVSV-based vaccine strategy represented a “promising approach to combating the novel coronavirus pandemic.”

Merck and IAVI said the rVSV vaccine platform uses an attenuated strain of vesicular stomatitis virus, a common animal virus that has been modified to express proteins that stimulate an immune response.

The plan, they continued, was to “leverage experience” gained with this platform during the development of Merck’s rVSV-based vaccine for Ebola Zaire.

Separately, Merck said it plans to acquire privately held Themis, a company focused on vaccines and immune-modulation therapies for infectious diseases and cancer, for an undisclosed cash payment.

Upon completion of the deal, Themis would then become a wholly owned subsidiary of Merck.

Source: CNBC

Coronavirus vaccine trials have delivered their first results — but their promise is still unclear

As coronavirus vaccines hurtle through development, scientists are getting their first look at data that hint at how well different vaccines are likely to work. The picture, so far, is murky.

On 18 May, US biotech firm Moderna revealed the first data from a human trial: its COVID-19 vaccine triggered an immune response in people, and protected mice from lung infections with the coronavirus SARS-CoV-2. The results — which the company, based in Cambridge, Massachusetts, announced in a press release — were widely interpreted as positive and sent stock prices surging. But some scientists say that because the data haven’t been published, they lack the details needed to properly evaluate those claims.

Tests of other fast-tracked vaccines show that they have prevented infections in the lungs of monkeys exposed to SARS-CoV-2 — but not in some other parts of the body. One — a vaccine being developed at the University of Oxford, UK, that is also in human trials — protected six monkeys from pneumonia, but the animals’ noses harboured as much virus as did those of unvaccinated monkeys, researchers reported1 last week in a bioRxiv preprint. A Chinese group reported similar caveats about its own vaccine’s early animal tests this month2.

Despite uncertainties, all three teams are pressing ahead with clinical trials. These early studies are meant mainly to test safety, but larger clinical trials designed to determine whether the vaccines can actually protect humans from COVID-19 could report in the next few months.

Still, the early data offer clues as to how coronavirus vaccines might generate a strong immune response. Scientists say that animal data will be crucial for understanding how coronavirus vaccines work, so that the most promising candidates can be identified quickly and then refined. “We might have vaccines in the clinic that are useful in people within 12 or 18 months,” says Dave O’Connor, a virologist at the University of Wisconsin–Madison. “But we’re going to need to improve on them to develop second- and third-generation vaccines.”

Immune response

Moderna’s vaccine, which is being co-developed with the US National Institute of Allergy and Infectious Diseases (NIAID) in Bethesda, Maryland, began safety testing in humans in March. The vaccine consists of mRNA instructions for building the coronavirus’s spike protein; it causes human cells to churn out the foreign protein, alerting the immune system. Although such RNA-based vaccines are easy to develop, none has yet been licensed anywhere in the world.

In its press release, the company reported that 45 study participants who received one or two doses of the vaccine developed a strong immune response to the virus. Researchers measured virus-recognizing antibodies in 25 participants, and detected levels similar to or higher than those found in the blood of people who have recovered from COVID-19.

Tal Zaks, Moderna’s chief medical officer, said in a presentation to investors that these antibody levels bode well for the vaccine preventing infection. “If you get to the level of people who had disease, that should be enough,” Zaks said.

But it’s not at all clear whether the responses are enough to protect people from infection, because Moderna hasn’t shared its data, says Peter Hotez, a vaccine scientist at Baylor College of Medicine in Houston, Texas. “I’m not convinced that this is really a positive result,” Hotez says. He points to a 15 May bioRxiv preprint3 that found that most people who have recovered from COVID-19 without hospitalization do not produce high levels of ‘neutralizing antibodies’, which block the virus from infecting cells. Moderna measured these potent antibodies in eight trial participants and found their levels to be similar to those in recovered patients.

Hotez also has doubts about the Oxford team’s first results, which found that monkeys produced modest levels of neutralizing antibodies after receiving one dose of the vaccine (the same regime that is being tested in human trials). “It looks like those numbers need to be considerably higher to afford protection,” says Hotez. The vaccine is a made from a chimpanzee virus that has been genetically altered to produce a coronavirus protein.

Hotez says that the vaccine being developed by Sinovac Biotech in Beijing seems to have elicited a more promising antibody response in macaque monkeys that received three doses, as reported2 in a 5 May paper in Science. That vaccine is comprised of chemically inactivated SARS-CoV-2 particles.

No one yet knows the precise nature of the immune response that protects people from COVID-19, and the levels of neutralizing antibodies made by the monkeys in the Oxford Study might be enough to protect people from infection, says Michael Diamond, a viral immunologist at Washington University in St. Louis, Missouri, who is a member of Moderna’s scientific advisory board. If not, a second injection would probably boost levels appreciably. “What we don’t know is how long they’ll last,” he adds.

Animal studies

Still more questions hover over experiments showing that vaccines can protect animals from infection. Moderna said its vaccine stopped the virus replicating in the lungs of mice. The rodents had been infected with a version of the virus that was genetically modified to let it attack mouse cells, which are not ordinarily susceptible to SARS-CoV-2, according to Zaks’s presentation. But the mutation affects the protein that most vaccines, including Moderna’s, use to stimulate the immune system, and this could change the animals’ response to infection.

The Oxford monkeys were given an extremely high dose of virus after receiving the vaccine, says Sarah Gilbert, an Oxford vaccinologist who co-led the study with Vincent Munster, a virologist at NIAID’s laboratories in Hamilton, Montana. This could explain why the vaccinated animals had just as much SARS-CoV-2 genetic materials in their noses as control animals, even though the vaccinated monkeys didn’t develop any signs of pneumonia. Administering high doses ensures that the animals are infected with the virus, but it might not replicate natural infections. The Oxford study did not measure whether the virus was still infectious, Diamond says, and the genetic material could represent virus particles inactivated by the monkeys’ immune response, or the viruses the researchers administered, rather than an ongoing infection.

Still, the result is “a concern” that raises the possibility that vaccinated people could still spread the virus, says Douglas Reed, an aerobiologist at the University of Pittsburgh Center for Vaccine Research in Pennsylvania. “Ideally, you want a vaccine that would protect against disease and against transmission, so that we can kind of break the chain,” he says.

One way to find out whether vaccines can prevent transmission would be to study them in animals that are naturally susceptible to the virus and seem capable of spreading it, such as ferrets and hamsters, says Reed. He and other researchers also point out that macaques display only mild symptoms of coronavirus infection, and they wonder whether vaccines should be trialled in animals that develop more severe disease.

Safety signs

Although assessing vaccines’ potential efficacy is difficult, the latest data are clearer on safety, say researchers. The Moderna vaccine caused few severe and no lasting health problems in trial participants. The vaccinated Oxford and Sinovac monkeys did not develop an exacerbated disease after infection — a key fear, because an inactivated vaccine for the related coronavirus that causes SARS (severe acute respiratory syndrome) showed signs of this in macaques5.

Stanley Perlman, a coronavirologist at the University of Iowa in Iowa City, says that the animal studies conducted so far can tell vaccine developers only so much. “People are doing as best they can,” he says. None of the data that he’s seen should dissuade developers from pressing on with trials in humans to determine whether the vaccines work, he says.

Moderna will soon begin a phase II trial involving 600 participants. It hopes to begin a phase III efficacy trial in July, to test whether the vaccine can prevent disease in high-risk groups, such as health-care workers and people with underlying medical problems. Zaks said that further animal studies, including some in monkeys, were under way, and that it wasn’t yet clear which animal would best predict whether and how the vaccine works.

The Oxford team has already enrolled more than 1,000 people in its UK trial. Some volunteers have received a placebo, so the trial could allow researchers to determine whether the vaccine works in humans over the coming months. The lack of safety problems in the team’s monkey study was reassuring, Gilbert says.

“We don’t really need any more data from animal trials to continue,” she says. “If we get human efficacy, we’ve got human efficacy, and that’s what matters.”

Source: Nature.com

COVID-19 And Its Impact On Clinical Trials

The monitoring of patients is perhaps the greatest ongoing challenge sponsors face during the pandemic. Filling noted the challenge for everyone involved with clinical trials will be providing efficient monitoring and oversight for the studies while also keeping patients safe. That will involve discovering new ways to perform those functions.

“In this day and age, we have great technologies available to us,” says Filling. “The good news is many companies were already performing remote and decentralized monitoring. The systems they need are already in place. For the companies that were not already doing that, there are resources available to help. I would also recommend turning to colleagues in the industry to help you navigate those processes.”

Sites Need Help

The situation taking place at many clinical sites seems to be changing day-by-day and even hour-by-hour. Trial monitoring has essentially ground to a halt at many of those clinics as the pandemic has sites focusing on protecting staff and patients. This situation makes remote monitoring essential. Filling believes sponsor companies need to step up and make sure their sites have the funding they need to put a successful remote monitoring approach in place. 

“Try to put yourself in their shoes,” she says. “They are dealing with a lot of issues right now. One site could have 15 sponsor companies lined up at their door suddenly asking them for remote monitoring services because it’s what regulators expect. Now is the time to give them the support they need.”

Davies agrees. She recently received a call from a friend who runs a site network asking how they should be handling patient monitoring and if they should even be open.

“From a site perspective, this is a crazy time,” says Kingsley. “Half our business has been put on hold, yet our workload is increasing. We are being inundated with phone calls, emails, and requests for updates from every sponsor client. We are dealing with 230 concurrent trials and all have unique requests. I have even spoken with several sponsors that are still demanding on-site visits take place. This is very disruptive. Sites are hurting financially and, suddenly, most of their work is unpaid activities.”

That workload Kingsley refers to is getting on calls with sponsors and CROs, performing remote monitoring visits, and performing other tasks that were not built into the original study budget. Those activities are going to impact site revenue. This is happening at a time when sites must reduce employee hours and even layoff some staff members. Those activities could also have an impact on clinical trials in the future, as it will be harder for sites to ramp up when the impact of the pandemic begins to fade.

“When you are forced to lay off staff, it can be hard to find experienced coordinators when you start re-hiring,” says Kingsley. “That means some sites might be forced to hire inexperienced staff to conduct the trials. I would encourage sponsors to get caught up on payments that might be owed to sites. Sites will need cashflow to weather this storm and continue to perform the requirements of your trial.”

A Site Stimulus

With the federal government considering a stimulus package for businesses and households, pharma might want to consider whether it’s time to discuss a site stimulus package. Some participants agreed that for pharma to salvage the data that exists on its trials, a stimulus is worth considering. That could take the form of a bonus or other financial incentives that would help sites get through this difficult time.

“It saddens me to hear that sponsors aren’t thinking about the additional cost implications for sites,” says Filling. “There is a lot of work, cost, and additional training involved with performing remote monitoring. Sponsors need to consider that and help offset the costs. That is the approach we are taking. We are considering everything our sites ask for and going back to them with what we can offer. Sites are our partners, and we will need to work together to get through this crisis.”

One additional staffing issue impacting clinical trials is the availability of therapeutic expertise. Young notes most clinical trials are in oncology, and most oncologists are classified as internal medicine. With the pandemic, many resident and attending staff that can treat COVID-19 patients are being pulled into general medicine clinics.

“They are needed to provide relief for the frontline providers who are running on fumes,” says Young. “We hear about the shortage of masks and other protective equipment, but we do not hear as much about the human dimension and what is happening with the frontline staff. They can only stay at work for so long before needing to rest. When those professionals get exposed to the virus, they must go into quarantine at home, which makes the situation even worse. I have a physician friend in San Diego who has set up a bedroom in her garage to protect her family. That causes a lot of mental stress. These are the stories we don’t hear about, but they will have an impact on clinical momentum.”

Document Everything

The panel agreed this is also a time for sponsors and sites to take a step back and outline their trial priorities. That outline should include what will need to be done to institute remote monitoring and what progress should be made in six months. It should also determine what actions are not essential to the trial and can be put on hold. If the pandemic persists after six months, a new outline will need to be completed. Sponsors should also consider producing a COVID-19 plan for each of their studies and distribute those plans to clinical sites. By putting things on paper there is a written plan for internal teams and sites to follow, which will keep everyone on the same page. Those plans should be fluid as they could be changing daily.

“This is certainly a time for sponsors to try thinking outside the box,” says Walsh. “When looking towards the future, it’s easy for companies to try and stay in a safe zone. One example might be the supply chain and getting products to patients. We need to keep in mind that there is always a patient at the end of that supply chain. The regulatory guidance was written in a way that leaves a lot of doors open for sponsors. Companies can now investigate things like direct–to-patient shipping of clinical supplies.  There is a real opportunity as sponsor companies are being presented with unprecedented flexibility.”

The panel also stressed the importance of documenting activities. Everyone agreed that although documenting actions is always important, it is now more important than ever. Guidance recently released by the FDA and EMA gives sponsors increased flexibility, but also stresses the need to document actions. Staffs should be trained to over-document thought processes and be prepared to explain it to regulators later. A good rule: ”If you don’t document it, it didn’t happen.”

Consider The Needs Of Every Patient

Kingsley states his sites are in the process of categorizing all trials, a process that involves examining the needs of the enrolled patients. If a trial involves monoclonal antibodies, for example, staff will determine the immune response of patients and thereby determine which trials present a higher risk for patients. A decision can then be made as to whether to continue the trial and how patients should be monitored. “The level of risk will determine whether patients come to the clinic or if we visit them at home,” says Kingsley.

Best practices that emerge during the pandemic will likely carry forward once COVID-19 has passed. Young hopes remote monitoring will be one of them. “Virtual engagement is where we are going and it will be a positive development for the industry,” he says. “This pandemic is really showing us a picture of what the future is going to look like. Remote monitoring is the tool that will allow us to effectively go to patients and continue to collect as much data as we can.”

Be aware that regulations and guidance differ from country-to-country. Actions in the U.S. may not be permissible in countries in Europe. In some countries, for example, clinic personnel are not permitted to visit a patient’s home. For sites that want to adhere to these regulations, this presents an additional challenge that must be overcome. It is also the perfect time to contact an IRB for advice.

Another consideration to protect the health of study participants would be to have separate waiting rooms. Davies notes hearing of a hospital that was putting all visitors in the same waiting room, including individuals who were in car accidents and those with symptoms of COVID-19.

“If you want to protect your patients that seems like something so simple” she says. “Every hospital or clinic should have two separate areas. That goes a long way towards protecting your patients who are simply there for a monitoring visit. For clinics that are not able to perform home visits that seems like the least they can do.”

Another option is to eliminate waiting rooms altogether. A clinic could have patients call from their car when they arrive, and then wait there until they are ready to be seen by staff members.

The panel also cautions sponsors to not forget about their research naive sites. Filling notes all sponsors have a small handful of sites that might be working on their first or second clinical trial. “This is a crazy time for them,” she says. “They don’t know how to deal with what is going on. You are the company that is teaching them how to navigate the research waters. This is a good time to reach out to them and listen to their concerns. They may not know what to do or where to go. You can be a very valuable resource to them right now.”

Finally, getting through this pandemic will certainly necessitate keeping all lines of communication open. For the time being, all kickoff meetings and investigator meetings will certainly be virtual. If you’re a site and have questions, don’t be afraid to ask. There must be an open dialogue between sponsors, sites, and CROs. With additional flexibility coming from the FDA and IRBs, now is the time for everyone to be discussing necessary changes to help patients and keep trials on track. As a sponsor, don’t hesitate to start those discussions.

“The silver lining is that we will be much better at doing this in the future,” says Kingsley. “The pain we are currently experiencing will accelerate the adoption of new technologies and new ways of conducting clinical research. It will change how we design protocols and how we look at contracting and budgeting. The future looks very exciting. We just have to survive today.”

Source: Clinical Leader

Veru Secures FDA Agreement to Initiate Phase 2 Study of VERU-111, Novel Drug to Combat COVID-19

Veru Inc. (NASDAQ: VERU), an oncology and urology biopharmaceutical company with a focus on developing novel medicines for the management of prostate cancer, announced that it has received FDA permission to initiate a Phase 2 clinical trial to assess the efficacy of VERU-111, a microtubule depolymerization agent, in combating COVID-19, the global pandemic disease caused by the novel coronavirus SARS-CoV-2.

VERU-111 is an oral, first-in-class microtubule depolymerization agent that targets the colchicine binding site of a and b tubulin subunits to inhibit microtubules and is currently under clinical development in prostate cancer.  Drugs that target microtubules have broad antiviral activity by disrupting the intracellular transport of viruses such as SARS CoV-2, along microtubules. Microtubule trafficking is critical for viruses to cause infection. Furthermore, microtubule depolymerization agents that target a and b tubulin subunits of microtubules also have strong anti-inflammatory effects including the potential to treat the cytokine release syndrome (cytokine storm) induced by the SARS-CoV-2 viral infection that seems to be associated with high COVID-19 mortality rates.

The Company met with FDA and received agreement on the clinical development program for VERU-111 as a potential dual antiviral and anti-inflammatory agent to combat COVID-19 under the new FDA program–Coronavirus Treatment Acceleration Program (CTAP).

The Phase 2 clinical trial is a double-blind randomized (1:1) placebo-controlled trial evaluating daily oral doses of VERU-111 versus placebo for 21 days in 40 hospitalized patients (VERU-111 20 subjects and placebo 20 subjects) who tested positive for the SARS-CoV-2 virus and are at high risk for Acute Respiratory Distress Syndrome (ARDS).  The primary efficacy endpoint will be the proportion of patients that are alive and without respiratory failure at Day 29.  Secondary endpoints include the measured improvements on the WHO Disease Severity Scale (8-point ordinal scale) which captures COVID-19 disease symptoms and signs including hospitalization to progression of pulmonary symptoms to mechanical ventilation as well as death. The study is expected to commence in the next 2 weeks.

VERU-111 has been shown to be well tolerated in the Phase 1b clinical study of 39 men as recently reported. VERU-111 is currently being administered as a 63mg daily dose in the ongoing Phase 2 clinical trial in men with metastatic castration resistant prostate cancer. The Phase 2 COVID-19 study will evaluate an 18mg oral daily dosing single treatment for 21 days.

“VERU-111 has demonstrated promising anticancer activity and a good safety profile in the recently completed Phase 1b metastatic castration resistant prostate cancer trial. We are now actively enrolling men into our Phase 2 prostate cancer clinical trial.  Although Veru is focused in prostate cancer and oncology, due to the urgency of the current global pandemic and the fact that VERU-111 has the potential to treat both SARS-CoV-2 infection and the associated reactive severe lung inflammation in COVID-19 patients at high risk for ARDS, the Company is duty-bound to pursue this COVID-19 indication even though it is not the primary focus of the Company,” said Mitchell Steiner, M.D., Chairman, President and Chief Executive Officer of Veru. “Based on the strong pharmacologic rationale as well as the preclinical and clinical studies supporting that VERU-111 may have both antiviral and anti-inflammatory effects along with acceptable safety against the SARS-CoV-2 virus, we will initiate this placebo controlled Phase 2 study in patients that have been hospitalized for SARS-CoV-2 at high risk for ARDS to improve symptoms and recovery and to avoid the need for mechanical ventilation. We plan to dose the first patient in the next 2 weeks,” said Dr. Steiner.

Because of the urgent need for effective and timely therapeutics to combat COVID-19, the Company has applied for significant grant funding through both The Biomedical Advanced Research and Development Authority of the US Department of Health and Human Services (BARDA) and The Defense Advanced Research Projects Agency of the US Department of Defense (DARPA) to expedite the clinical development program of VERU-111 for COVID-19. There is no guarantee that such grant funding will be provided.

Source: Veru, Inc.