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Dive Brief:

• FDA said Thursday it issued an emergency use authorization to spur availability of infusion pumps as the lifesaving machines and accessories are in short supply for COVID-19 patients. 
• The agency in early April issued guidance targeted at increasing access to breathing devices for patients who may require continuous infusion of medications, nutrition, and other fluids. But this week’s EUA takes the effort a step farther by allowing the manufacture, distribution, and use of pumps and accessories not otherwise cleared or approved for sale, or that require a modification that would ordinarily prompt a new premarket notification to FDA.
• The EUA in part covers infusion pumps with remote monitoring, remote manual control features, administration sets and other accessories with increased length designed to help maintain a “safe physical distance” between healthcare professionals and COVID-19 patients.

Dive Insight:

FDA said it’s concerned there are not sufficient quantities of infusion pumps and accessories available to meet America’s needs during the public health emergency. The EUA letter says the supply chain for products that meet the agency’s regulatory requirements has been “substantially stressed, with shortages already being observed in United States healthcare institutions, with demand exceeding the available supply.”

That assessment tracks with a warning last month by the Institute for Safe Medication Practices, an affiliate of the nonprofit ECRI Institute, that some healthcare organizations are “already experiencing unprecedented shortages of smart infusion pumps and dedicated administration sets, while others are still anticipating such shortages.”

The EUA, addressed to manufacturers, healthcare providers, hospital purchasing departments, and distributors, makes the case that there are “no adequate, approved, and available alternative” to the emergency use of the authorized pumps and accessories to treat COVID-19 patients. 

In comments emailed to MedTech Dive, ECRI CEO Marcus Schabacker, observed that the EUA “allows for temporary strategies by manufacturers to respond to COVID-19 outside the traditional 510(k) process in several ways, like bringing in certain pumps and accessories sold outside the U.S., allowing modifications to existing products, and specifically permitting PPE-conserving remote control features.”

While the EUA is meant to mitigate shortages of pumps and accessories, Schabacker recommended that healthcare facilities also “consider the post-EUA viability of products when negotiating a purchase.”

Nonetheless, George Gray, chief technology officer for infusion pump maker Ivenix, said the EUA has the potential to bring capabilities to the marketplace not generally available.

“Capabilities such as automating the delivery of infusions, automatically flushing medications through those long extension sets and a large, touchscreen that is easy to clean and can be seen from outside the room will make a big difference in the care of these patients,” Gray wrote to MedTech Dive.

However, Karen Giuliano, associate professor at the University of Massachusetts at Amherst’s College of Nursing & Institute for Applied Life Sciences, has concerns about the EUA’s manufacturer requirements for providing data on flow rate accuracy under various clinical conditions.

“To optimize the safety of IV medication administration during this emergency use authorization, it is imperative for IV infusion pump manufacturers to base their requested flow rate accuracy specifications on realistic clinical use scenarios,” said Giuliano, noting that providing complex care to COVID-19 patients is far from ideal.

Giuliano pointed out that some hospitals are currently placing infusion pumps in hallways, rather than in patient rooms, and using long tubing to help reduce nurses’ exposure to the virus and conserve PPE.   

“Various methods for increasing the length of IV tubing are now being used so patients can continue to receive important medications,” Giuliano said. But increasing the tubing length between the pump and the patient increases resistance, she added, likely causing an unknown and non-detectable decrease in flow rate.

Increasing the length of IV tubing also presents other challenges, including a significant increase in tubing dead space and additional opportunities for air-in-line, Giuliano said. “All of these factors can lead to portions of medication doses being left non-administered, representing various safety concerns for the patient.” 

Dive Brief:

• Health tech giant Philips and diagnostic imaging startup Caption Health announced FDA clearances this week for ultrasound tools they say could aid healthcare professionals in point-of-care imaging for patients infected with the novel coronavirus.
• Philips said Wednesday it received 510(k) clearance to market a range of its existing ultrasound products specifically for management of COVID-19-related lung and cardiac complications. Caption, which in February gained De Novo authorization for the first AI tool to help non-specialists take good-quality cardiac ultrasounds, said Tuesday FDA OK’d a software update ahead of schedule to enable more extensive guidance to healthcare providers wanting to take ultrasounds.
• The clearances coincided with Wednesday’s news that healthcare system Atrium Health has deployed mobile startup Butterfly Network’s point-of-care ultrasound device at COVID-19 testing centers and other high-priority sites.

  

• Dive Insight:

  The presence of cardiac complications has been a key datapoint in the triaging of COVID-19 patients since research on people hospitalized in Wuhan, China, identified it as a notable mortality risk factor. With healthcare systems stretched by the pandemic, the challenge is to effectively address that risk factor by quickly identifying and treating patients with cardiac complications.

  In that vein, FDA has made a flurry of decisions to increase access to relevant tools. On Monday, FDA gave emergency use authorization to a cardiac dysfunction detection algorithm marketed by Eko.

  A day later, Caption said FDA cleared an update to its software that walks users through the process of capturing ultrasound images. According to Caption, FDA took 25 days to review the update.

  The significance of the update to the management of coronavirus stems from the potential for the software to enable people without specialized echocardiography training to capture images of the heart at the point of care. In doing so, the software could reduce the need for sonographers to image COVID-19 patients, thereby limiting the number of healthcare workers exposed to the virus. 

  Similarly, Philips posted a notice Wednesday about the 510(k) clearance of a range of ultrasound products and software for use specifically in the imaging of COVID-19 patients. Philips, which posted guidance to healthcare providers in conjunction with the clearance, highlighted its handheld scanner and associated mobile app as devices of particular value in the response to the pandemic.

  News of the FDA clearances emerged around the same time as details of the expanded use of an existing ultrasound device. Butterfly said Atrium Health, a healthcare system with more than 40 hospitals, is using its portable whole-body ultrasound device Butterfly iQ at more than 30 locations, including COVID-19 testing centers, emergency departments and intensive care units. 

  Like other providers of ultrasound devices, Butterfly has seen its technology used to triage COVID-19 patients based on the condition of their hearts and lungs, as well as in ongoing monitoring of people infected with the coronavirus.

Shares in US-based Clovis Oncology have ticked up after the biotech became the first to get a PARP class drug approved in prostate cancer. 

The FDA has approved the company’s Rubraca (rucaparib) as monotherapy for patients with BRCA1/2 mutant castration-resistant disease (mCRPC), after treatment with an androgen receptor-directed therapy and a taxane-based chemotherapy. 

Clovis has therefore stolen a march on its rival AstraZeneca, which has its rival poly (ADP-ribose) polymerase inhibitor Lynparza under review with the FDA in castration resistant disease after treatment with just one hormonal agent. 

While this is a victory for Clovis in terms of timing, AstraZeneca could have an advantage if Lynparza is approved as it would effectively block doctors from prescribing Rubraca thanks to its use earlier in the disease treatment pathway. 

The FDA approved Rubraca under accelerated approval based on objective response rate (ORR) and duration of response (DOR) data from the multi-centre, single arm TRITON2 clinical trial.  

Continued approval for this indication may depend upon verification and description of clinical benefit in confirmatory trials. 

Clovis expects the TRITON3 clinical trial to serve as the confirmatory study for the Rubraca accelerated approval in mCRPC. 

Warning and precautions include myelodysplastic syndrome and acute myeloid leukaemia.

Approval for this third use for Rubraca is based on efficacy data from patients with mCRPC and a deleterious BRCA mutation (germline and/or somatic) enrolled in the multi-centre, single arm TRITON2 clinical trial. 

Major efficacy outcomes were ORR and DOR as assessed by a modified set of criteria allowing for blinded independent radiologic review. 

Confirmed prostate-specific antigen response rate is an additional pre-specified endpoint. 

Wassim Abida, medical oncologist, Memorial Sloan Kettering Cancer Center, and principal investigator for the TRITON2 study, said: “Rubraca is the first in a class of drugs to become newly available to patients with mCRPC who harbor a deleterious BRCA mutation. Given the level and duration of responses observed with Rubraca in men with mCRPC and these mutations, it represents an important and timely new treatment option for this patient population.” 

Standard treatment options include taxane chemotherapy, Bayer’s Xofigo (radium 223) and Dendreon’s pricey cell therapy Provenge (sipuleucel-T). 

The University of Oxford’s partnership with AstraZeneca on the development and distribution of Oxford’s COVID-19 vaccine is one of the leaders in this project. AstraZeneca reported it plans to manufacture as much as 30 million doses of the vaccine for the U.K. market by September, with expectations of 100 million doses by the end of the year. The U.K. would be the first country to get access to that vaccine, assuming it proves to be safe and effective.

In a statement today, U.K. Business Secretary Alok Sharma indicated the government was providing $79 million in funding. Another 18.5 million pounds will be provided to Imperial College London as human clinical trials progress.

Like most of the vaccines being developed, companies are working to scale up manufacturing in hopes that they will be proven safe and approved early, so they can be made and distributed globally as quickly as possible.

Oxford University’s Jenner Institute has a head start on the vaccine compared to most organizations, with the launch of a clinical trial of more than 6,000 people in May, showing not only that their COVID-19 vaccine is safe—typically the goal of smaller Phase I clinical trials—but effective, the goal of larger Phase II and Phase III clinical trials.

Their vaccine has been tested in six rhesus macaque monkeys at the National Institutes of Health’s Rocky Mountain Laboratory in Montana, that were then exposed to large volumes of the virus causing COVID-19. More than 28 days later, all six were still healthy.

One reason the Oxford group led by Adrian Hill, the Jenner Institute’s director, is ahead of the game is because Hill has spent most of his career on vaccine development, primarily on malaria. Jenner is one of the largest academic centers focused on nonprofit vaccine research. It even has its own pilot manufacturing plant that can make a batch of up to 1,000 doses. And as long ago as 2014, they had developed a template for mass production of the coronavirus vaccine, if it is effective, that could provide a million doses.

Once the pandemic hit, Hill put all the current work on other vaccines into storage and pivoted the institute’s resources and talent on COVID-19. Their vaccine alters the genome of a familiar virus, modifying it first to neutralize any disease effects and then force it to mimic the SARS-CoV-2 virus that causes COVID-19. Once injected, this “impostor” stimulates the immune system to battle and kill the COVID-19 coronavirus.

One of Hill’s colleagues at Jenner is Sarah Gilbert, who had been conducting work on another coronavirus, MERS. She had been conducting clinical trials of a vaccine against MERS, which is still common in Saudi Arabia. Once the genome of SARS-CoV-2 was published, she believed she had an opportunity to show how their approach could be both versatile and fast.

Part of the emphasis in today’s story is how AstraZeneca and the University of Oxford, while indicating the initial doses will be for the U.K.—which makes sense, in that both are in the U.K.— are concerned about assuring availability in poor and under-developed countries.

This issue has been exacerbated by March stories of President Trump allegedlyattempting to acquire German biotech company BioNTech’s vaccine exclusively for the U.S. market. BioNTech is now partnered with U.S.-headquartered Pfizer on the vaccine program.

About a week ago, Paris-based Sanofi’s chief executive officer Paul Hudson indicated that the U.S. would have first access to its COVID-19 vaccine because of the significant financial support it is receiving from the U.S. government. This raised a furor in other countries, particularly France, where the company is headquartered, and the U.K., where its partner in the vaccine endeavor, GlaxoSmithKline, is located.

Sanofi is now backing away from the pledge, where Hudson had said that because of the U.S.’s Biomedical Advanced Research and Development Authority (BARDA), part of the Department of Health and Human Services (HHS), funding, “The U.S. government has the right to the largest preorder because it’s invested in taking the risk.”

Although the statement at the time seemed fairly logical, Europeans did not see it that way. The office of French President Emmanuel Macron stated a vaccine is “a global public good, which is not submitted to market forces.”

The country’s Prime Minister Edouard Philippe tweeted, “Equal access for all to vaccine is not negotiable.”

Leaders from all over the world met for a virtual summit on Monday, May 4 to pledge billions of dollars to fund development of a vaccine against COVID-19, the disease caused by the novel coronavirus SARS-CoV-2. Noticeably absent was the United States.

The goal of the summit was to raise an initial $8.2 billion and to coordinate the development of vaccines that can then be equitably distributed around the world, including to poorer companies. Although China skipped the initial meeting, it had a presence at the May 4 meeting. Russia and India also did not participate.

President Trump’s Operation Warp Speed has a goal of making 100 million doses of a vaccine against COVID-19 available by November, 200 million by December and 300 million by January 2021. This aggressive and perhaps overly optimistic target has winnowed a possible 93 vaccine programs to 14 top candidates, which they expect will be further narrowed to six or eight.

In the U.S., Moderna today released positive interim Phase I data from its clinical trial of mRNA-1273, its mRNA vaccine against SARS-CoV-2, the novel coronavirus that causes COVID-19. The vaccine furthest along in human trials, showed positive results for both efficacy and safety, overall. So far, the data is very promising, both in its effectiveness and safety, although it’s very early for the safety data. On May 1, the company announced it had partnered with Switzerland’s Lonza on a 10-year strategic collaboration for larger scale manufacture of mRNA-1273, as well as other future Moderna projects.

As part of its scale-up efforts, the U.K. government indicated a vaccine production plant will open in the summer of 2021. The government provided 131 million pounds to accelerate development. The U.K. Vaccine Manufacturing and Innovation Center will have capacity to manufacture 70 million vaccine doses within four to six months of opening the permanent site at Harwell campus in Oxfordshire. It is a non-profit partnership between the University of Oxford, Imperial College and the London School of Hygiene and Tropical Medicine.

Moderna released positive interim Phase I data from its clinical trial of mRNA-1273, its mRNA vaccine against SARS-CoV-2, the novel coronavirus that causes COVID-19. The vaccine, furthest along in human trials, showed overall positive results for both efficacy and safety.

Moderna’s vaccine is a messenger RNA (mRNA) product, similar to a gene therapy. It involves injecting messenger RNA that codes for the virus’s Spike (S) protein. The patient’s cells then manufacture the S protein, which triggers the body’s immune system to recognize the virus itself.

Moderna received funding from the Biomedical Advanced Research and Development Authority (BARD)A, a division of the Office of the Assistant Secretary for Preparedness and Response (ASPR) within the Department of Health and Human Services (HHS). It is developing the vaccine in partnership with the U.S. National Institute of Allergy and Infectious Diseases (NIAID).

Data for immunogenicity—the ability of the vaccine to stimulate the immune system to recognize the virus—was available for two doses, 25 ug and 100 ug after two doses, with the immunogenicity tested on day 43, and the 250 ug dose after a single dose, tested at day 29. All the patients in this trial were healthy and between the ages of 18 and 55.

All the patients in the trial, 15 in each cohort, seroconverted by day 15 at a single dose—meaning their immune system was able to identify the virus. At day 43, which was two weeks after the second dose, all the patients with the 25 ug dose showed antibody levels in their blood at the same levels observed in the blood samples from people who have recovered from COVID-19. In patients receiving the 100 ug dose, the antibody levels were significantly higher at day 43 that that seen in recovered patients’ blood.

Currently, neutralizing antibody data (compared to binding antibody data, above) is only available for the first four patients in each of the 25 ug and 100 ug cohorts. The data, however, is consistent with the binding antibody data. The two different analyses are to determine how well the antibody attaches to the virus and how well it kills or neutralizes the virus.

In terms of safety, the vaccine was generally safe and well tolerated, similar to what was observed in other mRNA vaccine tests run by Moderna for other diseases. There was a grade 3 adverse event in the 25 ug and 100 ug dose cohorts, with a single patient in the 100 ug dose showing redness around the injection site. The most notable adverse events were observed at the 250 ug dose level, with three patients with grade 3 systemic symptoms, all after the second doses. The company notes all the side events were transient and self-resolving. No grade 4 adverse events or serious adverse events were reported.

In addition to data from the human clinical trial, NIAID conducted preclinical tests on mice, where the mice were given the vaccine, then later dosed with the actual SARS-CoV-2 virus. The vaccine prevented viral replication in the mice. The amount of neutralizing antibodies observed in the Phase I human participants at the 25 ug and 100 ug doses were consistent with the neutralizing titers that were protective in the mouse challenge experiments.

Based on the data, Moderna’s Phase II trial will be modified to evaluate two dose levels, 50 ug and 100 ug, with the goal of picking a dose for pivotal studies. The NIAID-led Phase I trial is being modified to include a 50 ug level dose across each of the three age groups. Moderna plans to the dose for the Phase III trial to be between 25 ug and 100 ug and expects the Phase III trial to launch in July.

“These interim Phase I data, while early, demonstrate that vaccination with mRNA-1273 elicits an immune response of the magnitude caused by natural infection starting with a dose as low as 25 ug,” said Tal Zaks, Moderna’s chief medical officer. “When combined with the success in preventing viral replication in the lungs of a preclinical challenge model at a dose that elicited similar levels of neutralizing antibodies, these data substantiate our belief that mRNA-1273 has the potential to prevent COVID-19 disease and advance our ability to select a dose for pivotal trials.”

The bottom line is this is very good and promising news, but it is based on very few patients and relatively little data. Still, the immunogenicity data suggests the vaccine will be effective in preventing COVID-19. It should be emphasized that the safety data, in particular, is very small and very early for typical vaccine development. Safety analysis in traditional vaccine development can take years. The safety data described in this trial appears promising, but, again, it is being described in a small group of patients who are otherwise healthy and relatively young. It’s not unusual, in clinical trials, for the high dose testing to be discarded—one of the primary purposes of a Phase I trial is to determine safe and effective dosing levels.

While developing and testing the vaccine, because of the pandemic Moderna is moving ahead with scaling up manufacturing and distribution plans. On May 1, the company announced it had partnered with Switzerland’s Lonza on a 10-year strategic collaboration for larger scale manufacture of mRNA-1273, as well as other future Moderna projects. NIAID is also working on a trial with older patients.

More than two years after first saying it would take its lead drug into a pivotal trial, Verona Pharma looks like it may finally follow through on that promise.

The UK biopharma says it has received a positive response from the FDA on its end-of-phase 2 data package for ensifentrine, intended to treat chronic obstructive pulmonary disease (COPD), and so will start a pair of phase 3 trials later this year.

Shares in Verona yo-yoed after the announcement but were in positive territory by the end of the day as investors digested the news, delivered alongside its quarterly business update.

Verona has been talking about advancing ensifentrine into late-stage development since reporting a successful phase 2b trial in 2018, but suffered a setback last year when another mid-stage trial missed its primary endpoint.

The dual PDE3/PDE4 inhibitor – formerly known as RPL554 and designed to dampen down inflammation in the lungs – is designed to be administered via a nebuliser to COPD patients as an add-on therapy to other drugs for the progressive lung condition.

In a statement, Verona said it now had “clarity from the FDA” on the key features of the planned phase 3 programme, including the dose that should be tested in the trials, the main outcome measures, and the patient population and study design.

The two ENHANCE trials have the same design, but the first (ENHANCE-1) will include longer safety follow-up than the second.

Each will test twice-daily nebulised ensifentrine 3mg as monotherapy and as an add-on to standard of care treatment with a single drug design to dilate the airways, such as a long-acting beta agonist (LABA) or long-acting muscarinic antagonist (LAMA), in around 800 moderate to severe COPD patients.

The primary endpoint will be improvement in lung function, measured by forced expiratory volume in one second (FEV1) over 12 hours, after 12 weeks of treatment, while secondary analyses will look at peak and trough FEV1 and COPD symptoms like shortness of breath, cough and chest infections.

COPD is a serious lung disease that affects millions of people, and trends to progress over time with patients frequently becoming highly debilitated.

It’s also proved a lucrative disease for drugmakers to target, with combination therapies delivered by inhaler based on beta agonists and inhaled corticosteroids (ICS) – such as GlaxoSmithKline’s Advair – making billions of dollars a year in sales.

Latterly treatment has started to shift towards triple therapy with LAMA, LABA and ICS drugs given together in products like GSK’s Trelegy and while there has been a slowdown in the respiratory market overall COPD was still a near $10 billion market in the US alone last year.

Verona reckons that there are more than a million COPD patients who can’t control COPD symptoms using current dual or triple therapies in the US, and ensifentrine could have a role to play in this sizeable group.

Japan’s Takeda has posted a surprise profit after its $59 billion merger with Shire just over a year ago, as the company shakes off the huge debts it incurred to get the deal done. 

Analysts had expected Takeda to turn a small loss after taking out huge bank loans worth around $32 billion to get the merger done in January 2019.

But Takeda has been busy selling off unwanted assets to cut its debts, such as over-the-counter businesses in Europe and the Middle East. 

The company has also benefited from the revenues that have been generated from Shire’s portfolio of rare disease drugs. 

Japan’s largest pharma said it expects to make around 355 billion yen ($3.3 billion) in operating profit for the year to March. 

For the financial year that ended in March, Takeda’s profit was around 100 billion yen ($92 million). 

Like many pharma companies Takeda has had to rapidly adapt to meet the demands of the COVID-19 pandemic. 

It has halted new drug trials and is now focusing on an investigational plasma-derived therapy for the disease codenamed TAK-888. 

It is working with an alliance of 10 global plasma companies to develop the therapy, based on immune cells derived from the blood of recovered coronavirus patients. 

Clinical trials for the new product, which is called CoVig-19, could begin in June. 

But the work to reshape the company after the merger has only just begun – Takeda has pledged to sell off non-core assets worth $10 billion. 

Last month it announced it would sell a portfolio of OTC and prescription products to Denmark’s Orifarm for about $670 million. 

In total assets sold last year were worth around $7 billion, according to Reuters, citing data from Refinitiv.

Most of this came from selling the dry eye drug Xiidra to Novartis for $5.7 billion, a deal that made sense for both parties. 

Xiidra was originally developed by Shire and fitted well with Novartis’ portfolio of ophthalmology products, while Takeda focuses on oncology, gastroenterology, neuroscience, rare diseases, and plasma-based therapies. 

Shares in Takeda ticked up following the announcement, while the rest of the market slid.

President and CEO Christophe Weber said: “In line with our values, Takeda is taking a lead in meeting the challenges of the COVID-19 outbreak. We initiated a global industry alliance, sharing our world-class plasma-derived Therapy R&D, plasma collection and manufacturing capabilities to work collaboratively with other global and regional plasma companies to accelerate development of CoVIg-19, a potential plasma-derived therapy for patients at risk from serious complications of COVID-19.

“Clinical trials are on track to begin in the summer and if successful, CoVIg-19 has the potential to be one of the earliest approved treatment options.”

Currently, Gilead Sciences has the only drug shown to be effective against COVID-19, antiviral drug Veklury (remdesivir). The company has now entered into licensing agreements with five generic drugmakers to make the drug available in 127 countries. They are Mylan, Cipla, Ferozsons Laboratories, Hetero Labs and Jubilant Lifesciences.

Gilead stated that the five companies will manufacture the drug for distribution in “low-income and lower-middle-income countries, as well as several upper-middle- and high-income countries.” The agreements are “royalty-free” until the World Health Organization (WHO) indicates the COVID-19 pandemic has ended or “until a pharmaceutical product other than remdesivir or a vaccine is approved to treat or prevent COVID-19, whichever is earlier.”

On April 30, the U.S. National Institute of Allergy and Infectious Diseases (NIAID) reported that its clinical trial of Gilead Sciences’ remdesivir in 1,063 COVID-19 patients met its primary endpoint. Patients receiving the drug recovered faster than similar patients who received placebo. The trial was known as the Adaptive COVID-19 Treatment Trial (ACTT). A day later the FDA granted the drug emergency use authorization.

Preliminary data from the trial indicate that patients receiving remdesivir had a 31% faster time to recovery than the placebo group. Patients in the placebo group had a median 15 days recovery, while patients receiving remdesivir recovered a median 11 days. The survival benefit was not statistically significant, 8% compared to 11.6% for the placebo group, although it is at least suggestive of a survival benefit.

“Although a 31% improvement doesn’t seem like a knockout 100%, it is a very important proof of concept,” said Anthony S. Fauci, director of NIAID. “What it has proven is that a drug can block this virus. This will be the standard of care.”

The company quickly began work to scale up its manufacturing, working to build a global consortium of pharma and chemical manufacturers in order to expand global capacity and production. The company believes it can get more than one million treatment courses manufactured by December 2020, with plans to produce several million in 2021. It plans to donate the current 140,000 courses that it expects to manufacture by the end of May.

The drug is intravenous and initially took close to a year to manufacture. They have since cut the time down, but it is still a lengthy process. It requires a series of chemical reactions that need to be completed in a specific sequence with a manual inspection of each vial at the end of the process. Some of the steps require unique ingredients with limited supplies and several of the steps can take weeks.

On May 7, Gilead announced that the Japanese Ministry of Health, Labour and Welfare (MHLW) granted the drug regulatory approval to treat COVID-19 under and “exceptional approval pathway.” It was based on data from the NIAID Phase III trial, Gilead’s Phase III SIMPLE trial and available data from the company’s compassionate use program, which included patients in Japan.

“The Japanese approval of remdesivir is in recognition of the urgent need to treat critically ill patients in Japan,” said Merdad Parsey, Gilead’s chief medical officer. “It is a reflection of the exceptional circumstances of this pandemic. We thank the Japanese Ministry of Health, Labour and Welfare for their leadership and collaboration, as we together work to respond to this public health emergency.”

The drug was originally developed to treat first hepatitis C, then tested against Ebola. It was not found to be particularly effective against that virus but has shown in vitro and in vivo antiviral activity in animal models against Ebola, Marburg, MERS and SARS.

Remdesivir is an RNA analog that closely resembles the adenine base that makes up RNA. When remdesivir is present, SARS-CoV-2 polymerase, an enzyme involved in viral replication, may incorporate remdesivir molecules instead of adenine, and insert them instead into the RNA strand. This “caps” the RNA strand, making it unable to manufacture more of the virus.

San Diego-based Sorrento Therapeutics is teaming up with New York City-based Mount Sinai Health System to develop an antibody cocktail called COVI-SHIELD to treat COVID-19.

The partnership is aimed at creating antibody products that could act as a “protective shield” against infection by the virus that causes COVID-19, SARS-CoV-2. COVI-SHIELD is expected to deliver a mixture of three antibodies that combined recognize three specific regions of the SARS-CoV-2 Spike protein.

The organizations believe that, if approved, COVI-SHIELD could be given for people returning to work and as a therapy for people exposed to the virus. The product is designed to be dosed as often as necessary, with each dose providing antiviral protection for up to two months.

Carlos Cordon-Cardo, the Irene Heinz Given and John LaPorte Given Professor and Chair of Pathology, Molecular and Cell-Based Medicine at the Icahn School of Medicine at Mount Sinai and his team screened about 15,000 people who may have had COVID-19 and recovered. They were looking for antibodies against the virus.

The screening leveraged a diagnostic test developed by Florian Krammer, professor of Microbiology at Icahn and authorized under an emergency use authorization by the U.S. Food and Drug Administration (FDA). Sorrento has access to plasma containing antibodies against COVID-19 in order to identify and produce monoclonal antibodies that have neutralizing activity against SARS-CoV-2.

“We’re working with pharma and biotech partners, such as Sorrento, to bring much needed therapies to the clinic,” said Erik Lium, executive vice president and chief commercial innovation officer of the Mount Sinai Health System. “We look forward to advancing the development of an effective antibody cocktail with Sorrento.”

This approach to preventing COVID-19 is gaining ground while the industry works to develop a vaccine against the disease or drugs are tested or developed. To date, 10 plasma companies globally have joined the CoVIg-19 Plasma Alliance, founded to accelerate development of a plasma-derived hyperimmune globulin therapy against COVID-19. The founding companies include Biotest, BPL, CSL Behring, LFB, Octapharma and Takeda, but has since added ADMA Biologics, BioPharma Plasma, GC Pharma and Sanquin.

The Alliance is also collaborating with the U.S. National Institute of Allergy and Infectious Diseases (NIAID) at the National Institutes of Health (NIH) to evaluate the safety, tolerability and efficacy of the hyperimmune therapy in adults with COVID-19. The trial is expected to launch this summer.

Sorrento is wrapping up the requirements to file an Investigational New Drug (IND) application to the FBI for the triple antibody combination therapy, with plans to initiate Phase I trials in the third quarter of this year.

“It is our belief that as we re-open the country and the economy, we will see local flare-ups of infectious spread of SARS-CoV-2,” said Henry Ji, chairman and chief executive officer of Sorrento Therapeutics. “Unfortunately, with coronaviruses, mutations are part of the equation and could render therapies ineffective over time. It is our intention to develop a triple antibody prophylactic and therapeutic agent that would shield healthcare workers and at-risk patients. This therapy is designed to be resistant to future virus mutations and, if approved, should be made available in support of testing, tracing, vaccination and other therapeutic approaches to allow for efficient management of viral infection by protecting those most at risk for up to two months at a time.”

Sorrento is an antibody-centric biopharma company typically focused on therapies for cancer and infectious diseases. Its immuno-oncology platforms include fully human antibodies (G-MAB library), clinical stage immuno-cellular therapies such as CAR-T and DAR-T, Intracellular targeting antibodies (iTAbs), antibody-drug conjugates (ADC) and clinical stage oncolytic virus, Seprehvir. Its antiviral therapies include COVIDTRAP, ACE-MAB, COVI-MAB, COVI-SHIELD and COVI-CELL.

Gilead Sciences has received approval from the Japanese Ministry of Health, Labour and Welfare (MHLW) for its antiviral drug remdesivir, under the brand name Veklury, to treat Covid-19 infection.

The decision falls under an exceptional approval pathway, which is similar to emergency use authorisation in the US.

Remdesivir is an experimental nucleotide analogue that showed broad-spectrum antiviral activity against various viral pathogens, including Ebola, Marburg, MERS and SARS, in-vitro and in-vivo in animal models.

In-vitro testing found that the drug is active against SARS-CoV-2, the novel coronavirus that causes Covid-19. The drug is currently being assessed in several Phase III clinical trials.

Gilead Sciences chief medical officer Merdad Parsey said: “The Japanese approval of remdesivir is in recognition of the urgent need to treat critically ill patients in Japan. It is a reflection of the exceptional circumstances of this pandemic.

“We thank the Japanese Ministry of Health, Labour and Welfare for their leadership and collaboration, as we together work to respond to this public health emergency.”

The Japanese approval is supported by results from the US National Institute of Allergy and Infectious Diseases (NIAID)’s global Phase III trial and Gilead’s Phase III SIMPLE trial in patients with severe Covid-19 manifestations.