Pharmaceutical Technology Editors

Inhalation contract development and manufacturing organization (CDMO), Vectura, has signed a pre-clinical development agreement with Australian cannabinoid medicines development company, Incannex Healthcare, according to a June 22, 2021 press release.

The agreement is pertaining to the pre-clinical development of IHL-216A, which is Incannex’s proprietary inhaled drug product for the treatment of traumatic brain injury (TBI). Under the terms of the agreement, formulation screening studies, manufacturing process optimization studies and stability assessments, and the manufacture of a laboratory-scale batch of IHL-216A to support toxicological studies will all be performed by Vectura.

IHL-216A, a combination drug that combines cannabidiol (CBD) with isoflurane, has been designed for administration shortly after head trauma to reduce secondary brain injuries. The combination of the drugs has been found by Incannex to act synergistically to reduce neuronal damage, neuroinflammation, and behavioral deficits that result from TBI.

Through a partnership between Incannex and the Monash Trauma Group at Monash University’s Department of Neuroscience in Australia, the protective effect of IHL-216A in sports concussion will be evaluated 

. Further development and progression of the IHL-216A will be performed by Vectura in parallel to the 

 study we have developed offers the opportunity to accelerate this program through to clinical development, and we look forward to working with Vectura, leveraging its wealth of experience in developing inhaled drugs, to progress this treatment to the next stage,” said Mark Bleackley, Incannex’s chief scientific officer, in the press release.

“The risks associated with head injuries in sport are becoming more widely recognized, and this project is at the forefront of research to not only make sports safer, but reduce the morbidity and mortality rates of people suffering serious head traumas,” added Mark Bridgewater, Vectura’s chief commercial officer, in the press release. “There are currently no pharmaceutical agents approved for the treatment of TBI, and we look forward to working with Incannex to develop a truly innovative and potentially life-saving drug.”

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Vectura has signed an agreement with Incannex Healthcare for the pre-clinical development of IHL-216A, an inhaled drug product for the treatment of traumatic brain injury.

Vectura Signs Agreement with Incannex to Advance TBI Treatment

on June 21, 2021 to help applicants of certain licensed biological products to determine the appropriate reporting category for a change in chemistry, manufacturing, and controls (CMC) information to an approved biologics license application (BLA). The guidance document includes general and administration information for evaluating and reporting changes and reporting categories based on a tiered-reporting system. The final guidance supersedes the July 1997 guidance, 

Guidance for Industry: Changes to an Approved Application: Biological Products.

Specifically, the guidance details reporting categories such as Prior Approval Supplement (PAS), Changes Being Effected in 30 Days/Changes Being Effected Supplements (CBE30/CBE), and Annual Report. The assessment of a change by the applicant and by FDA is also discussed. The document also provides the requirements for submitting changes to the agency and recommendations for reporting categories. Special considerations discussed in the document include process parameter changes and changes in raw materials suppliers.

The final guidance document is intended to help determine which reporting category is appropriate for a change in CMC information to an approved biologics application.

FDA Publishes Guidance on CMC Changes to an Approved Application 

 on June 17, 2021 for the development of treatments for breast cancer. The guidance offers recommendations for including premenopausal women in clinical trials of breast cancer drugs and biological products. The agency states in the guidance that menopausal status should not be the reason for exclusion from breast cancer clinical trials, and women with adequate estrogen suppression and postmenopausal women should be eligible for inclusion in clinical trials for drugs or combinations manipulating the hormonal axis.

The guidance does not address fertility and fertility preservations issues when treating premenopausal women with breast cancer. The agency recommends that a gynecologist be consulted during trial planning and monitoring.

The guidance provides recommendations for including premenopausal women in breast cancer clinical trials.

FDA Gives Guidance on Development of Breast Cancer Drugs

Clinical-stage pharmatech company, Exscientia, has entered into a binding agreement to acquire the artificial intelligence (AI) precision-based medicines company, Allcyte, it was announced in a June 15, 2021 press release.

Through the acquisition, Exscientia will expand its translational capabilities and Allcyte’s AI platform, which anticipates the effectiveness of cancer treatments in the clinic by analyzing the activity of drugs in live patient samples at single-cell resolution, will be expanded and extended into early discovery. Allcyte’s platform has been validated on multiple solid and hematological tumor types, as well as in non-cancerous tissues.

“Allcyte is able to demonstrate what therapy actually works in the individual patient with the most disease relevant screening platform we have seen,” said Andrew Hopkins, Exscientia’s CEO, in the press release. “Combining Allcyte’s platform with Exscientia’s technologies can redefine how drugs are developed, enabling integrated discovery and patient selection. Allcyte has assembled an outstanding team in Vienna and integration of the two platforms truly allows us to build our vision of patient-first AI.”

Nikolaus Krall, Allcyte CEO, added in the press release, “We are incredibly excited about the opportunity to immediately apply this technology to a wide range of drug discovery projects at Exscientia. This will also provide our team with the scale to expand our operations much more quickly to help provide important personalised, precision medicines to as many patients as possible.”

The acquisition transaction is currently under review by the Austrian regulatory process prior to closing. The financial terms of the agreement are for Exscientia to pay €50 million (US$59.4 million) in both cash and ordinary shares in Exscientia. Furthermore, Exscientia plans to expand the Vienna site as its European Union hub.

Exscientia has entered into a binding agreement to acquire the artificial intelligence precision-based medicines company, Allcyte.

Exscientia Enters Binding Agreement to Acquire Allcyte

Results of the Randomized Evaluation of COVID-19 Therapy (RECOVERY) trial have shown that Regeneron’s investigational antibody combination therapy reduces the mortality risk for hospitalized patients with severe COVID-19 whose immune response has not started naturally. The trial results were released in a June 16, 2021 press release.

Regeneron’s combination therapy comprises two monoclonal antibodies—casirivimab and imdevimab—which specifically bind to two different sites on the coronavirus spike protein. In previous studies on non-hospitalized patients, the therapy was shown to reduce viral load, shorten the time to resolution of symptoms, and significantly reduce the risk of hospitalization or death.

Preliminary results of a small trial of hospitalized patients suggested that the combination therapy would provide a clinical benefit to hospitalized patients who had not mounted a natural immune response (seronegative). The RECOVERY trial included 9785 patients who were hospitalized with COVID-19, which is a sufficiently large patient population to determine whether the treatment reduces mortality.

Of the patients included in the trial, approximately one-third were seronegative at baseline. For these patients, the combination therapy was found to significantly reduce the primary outcome of 28-day mortality. This result was not comparable with patients who were seropositive at baseline.

“These results are very exciting. The hope was that, by giving a combination of antibodies targeting the SARS-CoV-2 virus, we would be able to reduce the worst manifestations of COVID-19. There was, however, great uncertainty about the value of antiviral therapies in late-stage COVID-19 disease,” said Sir Peter Horby, professor of Emerging Infectious Diseases in the Nuffield Department of Medicine, University of Oxford, and joint chief investigator for the RECOVERY trial, in the press release. “It is wonderful to learn that even in advanced COVID-19 disease, targeting the virus can reduce mortality in patients who have failed to mount an antibody response of their own.”

“We now know that this antibody combination is not only bad for the virus, but it is also good for the sickest patients who have failed to mount a natural immune response of their own,” added Sir Martin Landray, professor of Medicine and Epidemiology at the Nuffield Department of Population Health, University of Oxford, and joint chief investigator, in the press release. “That is excellent news—it is the first time that any antiviral treatment has been shown to save lives in hospitalized COVID-19 patients. We are incredibly grateful to the many NHS staff and patients who have contributed to today’s discovery.”

RECOVERY trial results have shown that Regeneron’s investigational antibody combination therapy reduces the mortality risk for seronegative hospitalized patients with severe COVID-19.

Regeneron’s Antibody Combination Therapy Reduces COVID-19 Mortality Risk

The US National Institute of Allergy and Infectious Diseases (NIAID) 

 on June 17, 2021 that the Biden administration will be investing more than $3 billion for the development and manufacturing of antiviral medicines. The National Institutes of Health (NIH), NIAID, and the Biomedical Advanced Research and Development Authority (BARDA) will collaborate to respond to the urgent need for COVID-19 antivirals through the Antiviral Program for Pandemics. The plan will spur the availability of lifesaving COVID-19 medicines and prepare for future viral threats by building discovery and development platforms for antivirals for other viruses with the possibility of becoming a pandemic.

NIH will evaluate, prioritize, and advance antiviral candidates to Phase II clinical trials as part of the plan. More than $300 million will be provided for research and lab support, almost $1 billion will be provided for preclinical and clinical evaluation, and nearly $700 million will be provided for development and manufacturing through NIAID and BARDA. Additionally, $1.2 billion will support the creation of Antiviral Drug Discovery (AViDD) Centers for Pathogens of Pandemic Concern for the discovery and development of antiviral drugs. The centers will first target coronaviruses and then expand to other viruses with pandemic potential.

“New antivirals that prevent serious COVID-19 illness and death, especially oral drugs that could be taken at home early in the course of disease, would be powerful tools for battling the pandemic and saving lives,” said Dr. Anthony Fauci, chief medical adviser to the President and NIAID Director, in a 

. “Through multidisciplinary collaborations among leading scientists in academia and industry, this investment from the American Rescue Plan to create the Antiviral Program for Pandemics will help inspire medical innovation and build on the extraordinary success we have seen in developing the COVID-19 vaccines.”

“This plan builds on the long, successful partnership between BARDA and NIH to develop vaccines, therapeutics and diagnostics, from combatting Ebola, anthrax and smallpox, to now tackling COVID-19,” said BARDA Director Gary Disbrow, PhD, in the release. “Throughout this public health emergency, we have worked with industry to develop treatments to reduce severe illness, hospitalizations, and deaths, and this proposal will help us go even further to accelerate and deliver more safe and effective treatments that are easy to administer.”

The US government will invest $3 billion from the American Rescue Plan into a COVID-19 antiviral development strategy.