Moderna to begin Phase 3 of COVID-19 vaccine study in July

Moderna (NSDQ:MRNA) announced today that it expects to begin dosing in Phase 3 of the clinical trial for its COVID-19 vaccine candidate in July.
The Cambridge, Mass.-based biotech company said in a news release that it finalized the Phase 3 study protocol for the mRNA-1273 COVID-19 vaccine candidate based on feedback from the FDA. The randomized, 1:1 placebo-controlled trial is expected to include approximately 30,000 enrolled U.S. participants in collaboration with the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH).
Source –


Milken Institute Teams with First Person to Explain the Race to a COVID-19 Vaccine

WASHINGTON–(BUSINESS WIRE)– The Milken Institute, the nonprofit, nonpartisan think tank, and First Person, a San Francisco design and storytelling company, together tell the urgent story of the global race for a COVID-19 vaccine in a newly released interactive experience at:
Developed by First Person®, the web-based tool is the culmination of a nearly three-month-long effort tracking treatment and vaccine candidates for COVID-19 undertaken by FasterCures, a center of Milken Institute. When it first launched, FasterCures identified 38 vaccine candidates. As of today, there are 161 vaccines in development, with 10 in clinical trials.
“Developing a safe vaccine that can be widely accessed is both necessary and extraordinarily complex,” said Esther Krofah, Executive Director at FasterCures. “We are thrilled that First Person has been able to bring our comprehensive vaccine tracker to life in a way that educates the public and gives the medical research community a new tool to better understand the race toward a COVID-19 vaccine.”
The interactive platform is updated regularly and takes the viewer through a narrative including:

  • An overview of the number of vaccine candidates currently in development
  • A timeline of vaccine development and how vaccines work
  • The steps for taking a vaccine from ideation to commercialization, and then to widespread use

“Our intent with this project was to answer the question of how long it would take to develop a COVID-19 vaccine,” said Drew Fiero President and CEO of First Person. “The comprehensive, neutral, and consistently updated data from FasterCures allowed us to leverage our storytelling capabilities to do just that through a visually compelling, interactive experience.”


‘Uniquely Worse Than I Can Remember’: 2 Million COVID-19 Cases

With the U.S. surpassing 2 million cases of COVID-19, infectious disease experts have learned a tremendous amount about SARS-CoV-2’s transmissibility, the effects of infection, and how (or how not) to treat it.
David Aronoff, MD, of Vanderbilt University Medical Center in Nashville, told MedPage Today that non-pharmaceutical interventions, such as masking and social distancing, successfully altered the virus’s transmission dynamics, specifically the average number of people one carrier infects, known as R0.
“A lot of people are understanding that’s not a fixed value for a particular virus, that you can change the R0 by initiating public health interventions. That’s how you flatten the curve.”
Aronoff noted the R0 for SARS-CoV-2 was initially thought to be in the range of 4 to 6, but now most states have pushed it closer to 1.
That was achieved “by figuring out the need to create distance between people, that we need to ask people to wear cloth masks … to limit dispersal of respiratory droplets,” he said. “It’s helped us slow transmission of this virus.”
The recent dust-up involving World Health Organization (WHO) statements on asymptomatic and presymptomatic transmission aside, Peter Hotez, MD, PhD, of Baylor College of Medicine in Houston, pointed to “high transmissibility of COVID-19, even among potentially asymptomatic individuals.”
Matthew Spinelli, MD, of the University of California San Francisco, said this type of transmission is part of why this epidemic has been so difficult to control in the U.S.
“Social distancing and universal masking are supported by what we know about the virus, that viral load tends to rise to its peak before symptoms occur,” he said.
Spinelli emphasized the importance of early social distancing and sheltering in place, adding, “We learned the hard way that waiting a week later probably made a huge impact on the New York epidemic.”
Even with the country “reopened,” Hotez noted how some still “resist social distancing and contact tracing.”
“With the reopening in May we are now seeing significant upswings in COVID-19 cases in Arizona, Texas, Utah [and] elsewhere in the American Southwest,” he said.
‘Unusual’ Complications
Aronoff cited the vascular morbidity as an unusual complication of COVID-19, which is not typically seen in other respiratory diseases, or even infectious diseases. These complications included ischemia, thrombosis, and strokes, including in young people.
“Any disease that puts people in hospital beds is associated with increased risk of deep vein thrombosis, but I think we’re seeing a lot more vascular complications with this particular infection than any other infectious disease,” he said. “Strokes, arterial thrombi and massive clot burdens are uniquely worse than I can remember in other infectious diseases.”
Spinelli also commented on the “unusual” hematologic effects in many patients.
“It’s a virus the immune system’s never seen before, so we’ve seen some interesting sequelae of disease” including Kawasaki disease-like manifestations in children, he said.
Aronoff said that people have left the hospital with “severe lung damage,” often requiring oxygen at discharge. One survivor was just reported to have undergone a double lung transplant.
In addition, clinicians have seen patients with unusual symptoms, such as anosmia, change in taste, or fevers for long periods of time.
For patients with severe illness, proven treatment is still centered on the supportive care routinely given for other pneumonias. The one specific treatment for COVID-19 showing solid evidence of efficacy so far is the antiviral agent remdesivir, Spinelli said.
“It’s not a game-changer, but it does open a pathway to other therapeutics,” he said — ideally, an “oral agent given early in the disease and/or a more effective antiviral agent” that could head off the pulmonary inflammation causing the worst sequelae.
All three experts agreed a vaccine is going to play a huge role in stopping COVID-19 transmission.
“Another big unknown is whether herd immunity is really around 60%-70% or whether the herd immunity threshold may actually be much lower due to heterogeneity in susceptibility or contact,” Hotez said. But he expressed concern that anti-vaccination activists, who were already mobilizing even before any actual products were developed, will obstruct population-level protection. “We may reach a point where insufficient numbers of people will agree to become vaccinated in order to achieve herd immunity,” he said.
Spinelli said if there is a second wave, early social distancing and non-pharmaceutical interventions must be brought back to help contain it.
“We need public health authorities and the government to work together. The important thing is to act quickly,” he said. (In Washington, however, there seems to be little appetite for a renewal of lockdown measures. Treasury Secretary Steven Mnuchin told CNBC flatly that “we can’t shut the economy down again” irrespective of what happens with the pandemic.)
Aronoff said if there was a time machine to go back to the beginning of 2020, there should have been different messaging about masks, the use of testing, and public health interventions.
“We are really going to need to see the results of more pharmacologic treatment trials and vaccine studies and we’re going to have to do a lot of work to understand how to improve population health,” he noted.
And even if the estimates of those who have been exposed to COVID-19 are off by 10-fold, it’s still only 5% to 6% of the population — meaning the vast majority could still be swept up in a second wave.
“Gone are the days of the handshake, the kiss on the cheek, the hug for welcoming strangers,” Aronoff said.



FDA Action Alert: Viela, Merck, Epizyme, Evoke and Regeneron

The next two weeks are busy ones for the U.S. Food and Drug Administration (FDA). Here’s a look at PDUFA dates for this period.
Viela Bio’s Inebilizumab for NMOSD
Gaithersburg, Maryland-based Viela Bio has a target action date of June 11 for its Biologics License Application (BLA) for inebilizumab for neuromyelitis optica spectrum disorder (NMOSD). The drug has previously received Orphan Drug and Breakthrough Therapy designations from the FDA.
Inebilizumab, Viela Bio’s lead product, is a humanized monoclonal antibody that targets and depletes CD-19-expressing B-cells. The byproduct of the B-cells, called plasmablasts, make up the autoantibody pathway, which can lead to severe autoimmune diseases like NMSOD.
In the N-Momentum pivotal clinical trial of the drug, it showed a significant reduction in risk of NMOSD attack and on measurements of worsening disability, hospitalizations and new central nervous system MRI lesions. The company also has plans to evaluate the drug in other autoimmune diseases, including myasthenia gravis, IgG4-related disease and kidney transplant desensitization.
Yet Another Merck Indication for its Checkpoint Inhibitor Keytruda
Merck has a target action date of June 16 for its supplemental BLA (sBLA) for Keytruda (pembrolizumab) for adult and pediatric patients with unresectable or metastatic solid tumors with tissue tumor mutational burden-high (TMB-H) greater than or equal to 10 mutations per megabase, as determined by an FDA-approved test, who have progressed after previous treatment and who have no satisfactory alternative treatment options. The application was partially based on data from the Phase II KEYNOTE-158 trial. Keytruda is involved in more than 1,000 clinical trials alone or in combinations in a broad range of cancer indications.
Epizyme’s Tazverik for Follicular Lymphoma
Cambridge, Massachusetts-based Epizyme has a target action date of June 18 for Priority Review of its supplemental New Drug Application (sNDA) of Tazverik (tazemetostat) for relapsed or refractory follicular lymphoma (FL) patients who have had at least two previous lines of systemic therapy. Tazverik is a methyltransferase inhibitor approved for adults and pediatric patients aged 16 years and older with metastatic or locally advanced epithelioid sarcoma not eligible for complete resection. It was approved for that indication in January 2020.
“Follicular lymphoma is an incurable disease for which patients are in need of a safe, durable treatment option,” said Shefali Agarwal, chief medical officer of Epizyme in February. “If approved, we believe Tazverik could become an important new option for these patients and their physicians.”
Evoke Pharma’s Gimotti for Recurrent Diabetic Gastroparesis
Solana Beach, California-based Evoke Pharma has a target action date of June 19 for its resubmission of its 505(b)(2) NDA for Gimoti. Gimoti is the company’s nasal spray for the relief of symptoms in adult women with acute and recurrent diabetic gastroparesis. Gastroparesis is a debilitating, episodic condition marked by slow or delayed gastric emptying of the stomach’s contents after meals. It often causes nausea, vomiting, abdominal pain and bloating. It is much more common in women.
On May 20, Evoke indicated the FDA had conditionally accepted the brand name of Gimoti.
“Gimoti’s nasal spray delivery is designed to facilitate drug absorption by allowing Gimoti to bypass the dysfunctional GI tract in patients with this disease,” said Dave Gonyer, president and chief executive officer of Evoke. “We continue to believe Gimoti, if approved, will provide an important new product that has the potential to help treat patients suffering from gastroparesis.”
Nabriva’s Contepo for Complicated Urinary Tract Infections
Dublin, Ireland-based Nabriva Therapeutics has a target action date of June 19 for its NDA resubmission for Contepo (Fosfomycin) for the treatment of complicated urinary tract infections (cUTIs). Contepo is a potential first-in-class intravenous antibiotic in the U.S. for cUTIs. The NDA resubmission is supported by data from a pivotal Phase II/III ZEUS trial, which met the primary endpoint of statistical non-inferiority to piperacillin/tazobactam in patients with cUTI, including acute pyelonephritis.
Regeneron’s Dupixent 300 mg Auto-Injector
Regeneron Pharmaceuticals has a target action date of June 20 for its sBLA for the 300 mg auto-injector for Dupixent (dupilumab). Dupixent is a subcutaneous injection indicated for various allergic and inflammatory diseases, including children age 12 years or older with moderate-to-severe atopic dermatitis; maintenance treatment with other asthma medicines for moderate-to-severe eosinophilic or oral steroid dependent asthma in patients aged 12 years and older; maintenance treatment of CRSwNP in adults. It is also being evaluated for a broad range of clinical programs for allergic and type 2 inflammatory conditions, including pediatric asthma, pediatric atopic dermatitis, eosinophilic esophagitis, chronic obstructive pulmonary disease, bullous pemphigoid, prurigo nodularis, chronic spontaneous urticaria, and food and environmental allergies. The drug is being jointly developed by Regeneron and Sanofi.
On May 26, the FDA approved Dupixent for children aged 6 to 11 years with moderate-to-severe atopic dermatitis.
“This approval brings the paradigm-changing efficacy and established safety profile of Dupixent to children with moderate-to-severe atopic dermatitis,” said George D. Yancopoulos, co-founder, president and chief scientific officer of Regeneron. “This young, vulnerable population struggles with debilitating symptoms and disease covering over half of their body, impacting them and their families who spend countless hours helping them manage their disease.”


Biopharma Update on the Novel Coronavirus: June 8

FDA Actions
Reissued EUAs: The FDA reissued EUAs revising which types of respirators can be decontaminated for reuse.
Availability and Capability of Non-Invasive Monitoring Devices: The FDA issued new guidance that expands the availability and capability of non-invasive monitoring devices. This guidance replaces March 20, 2020 guidance.
Diagnostics Update: The FDA has worked with more than 400 test developers who have submitted or plan to submit EUA requests to detect COVID-19. Also, 124 individual EUAs have been issued, which includes 106 molecular tests, 17 antibody tests and 1 antigen test.
Genomics company Phosphorous, based in New York, announced I received Emergency Use Authorization from the FDA for its COVID-19 saliva test that features at-home sample collection. This is only the second at-home unsupervised saliva test approved so far by the FDA.

Testing Therapies, Antivirals and Vaccines

An oncology drug could prove to be effective against COVID-19. Researchers with The U.S. Oncology Network discovered AstraZeneca’sCalquence (acalabrutinib) benefited a small number of patients who have severe infections of the novel coronavirus.
Junshi Biosciences announced that the first healthy volunteer has been dosed in the Phase I clinical study of JS016 in China. JS016 is the first SARS-CoV-2 neutralizing antibody to enter clinical trials in China. Junshi and Eli Lilly and Company are collaborating to co-develop JS016 globally.
RELIEF Therapeutics and NeuroRx have expanded their Phase II/III clinical trial of RLF-100 for COVID-19 to include patients receiving high flow oxygen and noninvasive ventilation (CPCP), in addition to patients on ventilators. RLF-100 (Aviptadil) is a formulation of synthetic human Vasoactive Intestinal Peptide (VIP).
Ashvattha Therapeutics, a biotech company located in the Bay area, is developing its drug, OP-101, an anti-inflammatory drug with the potential to help fatal inflammatory events associated with coronavirus infections. The company is entering Phase II clinical trials with the hope to have interim analysis done at the end of September.
Applied DNA Sciences provided an update in the development of a linear-DNA form of COVID-19 vaccine candidates with partner Takis Biotech. The first injections of plasmid-based DNA vaccine candidates produced neutralizing antibodies in test animals. Linear DNA versions of the candidates began dose-response trials and results are expected to be published in June 2020.

Company Actions

Sherlock Biosciences and Integrated DNA Technologies (IDT) entered a strategic partnership to manufacture CRISPR SARS-CoV-2 diagnostic and research products. Sherlock recently received EUA from the FDA for its SARS-C0V-2 test kit. It is the first CRISPR-based diagnostic test to receive EUA for COVID-19.
SiO2 Materials Science signed a $143 million deal with the DoD’s Joint Program Executive Office for Chemical, Biological, Radiological, and Nuclear Defense (JPEO-CBRND) in partnership with BARDA to accelerate production scale-up of the company’s primary packaging platform for storing COVID-19 vaccines and therapeutics. The company’s materials science is a combination of a plastic container with a microscopic thin, undetectable to the naked eye, pure glass coating for biologic drugs and vaccines.

Other Industry News

To achieve population-level COVID-19 vaccinations, first rebuild trust. Poll after poll shows that many Americans – 30% to 50% – are unwilling to be vaccinated against COVID-19 once a vaccine becomes available. Meanwhile, officials are banking on widespread vaccination to allow society to return to normal, without masks or social distancing. We can’t return to normal without population-level vaccinations, though.
A paper published in Cell Systems shows researchers have identified 27 proteins in the blood of COVID-19 patients that could potentially be used to treat the disease and help to decide which type of treatment to use, as reported by ScienceDaily.
In a research letter in JAMA Network Open, a blood test used to find hypercoagulability accurate may predict clotting risk in patients with severe COVID-19.
Louis J. Ignarro, Nobel Prize-winning researcher and UCLA Distinguished Professor Emeritus pointed to a recent study by Ackermann et al. in the New England Journal of Medicine, “Pulmonary Vascular Endothelialitis, Thrombosis, and Angiogenesis in COVID-19” supports the use of nitric oxide as a treatment for COVID-19. Essentially, he said, “this study shows that the coronavirus causes destruction of the capacity of blood vessels in the lungs to produce nitric oxide (NO).”



Respira Technologies Seeks Drug Candidates for its Nebulizer

Respira Technologies (West Hollywood, Calif.) announced the launch of a pharmaceutical-focused commercial development program for its RespiRx drug-delivery device platform. RespiRx is a portable, handheld vibrating mesh nebulizer designed for local and systemic treatment and can operate in any position held by the patient. Current-generation nebulizers are gravity-fed, which limits usage and can lead to improper use and/or lower rates of drug-delivery efficacy, according to the company.
RespiRx also has a pre-filled cartridge that includes a disposable piezo element and the drug compound suspended in an aqueous solution. This format is designed to improve convenience and eliminate patient error and misuse due to the lack of proper cleaning. The cartridge is programmable for precise dose delivery and is Bluetooth-enabled for dose delivery tracking, measurement, and electronic medical record data collection for the healthcare provider.
Target indications for the RespiRx include the treatment of asthma, COPD, potential vaccine delivery, pain management, nicotine replacement therapy, and investigative new drugs such as inhalable insulin.
“The current landscape of drug delivery platforms lacks the patient-focused attributes necessary to address the high rate of patient misuse of daily controller medications, including nebulizers,” said CEO Mario Danek in a news release, “The RespiRx was created to address the patient’s unmet needs for improved care.”
The company is backed by venture firms DG incubation, Evolution VC Partners, and Poseidon Asset Management.


Merck, IAVI Work to Develop COVID-19 Vaccine

Merck (NYSE:MRK) and IAVI announced today that they are collaborating to develop an investigational vaccine against SARS-CoV-2 for preventing COVID-19.

The vaccine candidate is slated to use the recombinant vesicular stomatitis virus (rVSV) technology used as the basis for Merck’s Ervebo Ebola Zaire virus vaccine, which was the first such vaccine to be approved for use in humans, according to a news release. Merck also signed an agreement with the Biomedical Advanced Research and Development Authority (BARDA), part of the U.S. Dept. of Health and Human Services, to provide funding for the collaboration.

“COVID-19 is an enormous scientific, medical, and global health challenge,” Merck Research Laboratories president Dr. Roger Perlmutter said in the release. “Merck is collaborating with organizations around the globe to develop anti-infectives and vaccines that aim to alleviate the suffering caused by SARS-CoV-2 infection.

“Merck and IAVI are eager to combine our respective strengths to accelerate the development of an rVSV vaccine candidate, with the goal of blunting the trajectory of the COVID-19 pandemic.”

IAVI and Merck will now come together to further the development and evaluation of the vaccine candidate designed and engineered by IAVI scientists, which is currently in preclinical development with clinical study plans set for later this year. Merck is responsible for leading regulatory filings around the world, while both companies intend to work together to develop the vaccine and make it accessible and affordable if it is approved.

Development work on the vaccine is being done at IAVI’s design and development laboratory in Brooklyn, New York, as part of an effort to develop rVSV vaccines for HIV, Lassa fever, Marburg, and Ebola Sudan disease.

“We believe an rVSV-based vaccine strategy represents a promising approach to combating the novel coronavirus pandemic and look forward to implementing an accelerated development program, together with Merck, to evaluate the potential of our vaccine candidate against SARS-CoV-2,” IAVI President & CEO Dr. Mark Feinberg said. “The collaboration between Merck and IAVI represents an innovative partnership model and approach to utilize our joint capabilities in complementary and synergistic ways to address this difficult global health challenge.”

Lawyers at White & Case LLP, led by partner Andres Liivak and associate Elle Davis, advised IAVI in the process of developing the collaboration with Merck on this vaccine candidate.



Phlow lands $354m government contract for COVID-19 medications

Phlow announced today that it received $354 million in U.S. government funding to manufacture essential medicines at risk of shortage, including those involved in the COVID-19 pandemic response.
Richmond, Va.-based Phlow’s manufacturing is being funded by the Biomedical Advanced Research and Development Authority, part of the office of Assistant Secretary for Preparedness and Response at the U.S. Dept. of Health and Human Services.