Pharmaceutical Technology Editors

On Aug. 18, 2021, Corning announced the preview of its new Corning Ascent fixed bed reactor (FBR) system at the 2021 Bioprocessing Summit, which ran Aug. 16–19 in Boston. The FBR system is a high-density, automated bioproduction platform that is designed to enable the large-scale manufacture of adherent cells needed to create advanced therapies. The system is said to lower the cost of production, according to a company press release.

Corning developed the Ascent FBR System to specifically achieve high-yield efficiency in adherent cell lines while allowing for the scale and automation typically associated with suspension platforms. The system has demonstrated greater than 90% recovery, viability, and transfection efficiency in cell and gene therapy workflows, including viral vector production, the company stated in the press release. The system has a broad range of applications, such as regenerative medicines, that require large quantities of cell harvesting. In addition to this initial benchtop system previewed at the Bioprocessing Summit, Corning plans to launch larger Ascent FBR formats ranging from 1 m

“The cell and gene therapy industry has an urgent need for a scalable, cost-efficient way to manufacture cells and cell-based products,” said John Tobin, vice-president and general manager of Corning Life Sciences, in the press release. “With the Ascent FBR System, we have created a new technology platform designed to scale up bioproduction; significantly improve yield; and reduce the time, cost, and waste involved in getting advanced therapies to market.”

“Corning’s Ascent FBR System has the potential to drive further efficiencies in the bioproduction process so that our customers can more quickly and more economically deliver potential treatment options that were once thought impossible,” Tobin added in the press release.

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Corning’s new Ascent fixed bed reactor (FBR) system is an automated bioproduction platform designed to significantly improve yields and reduce bioproduction costs.

Corning’s New Cell and Gene Therapy Platform Demonstrates Large-Scale Bioproduction

Werewolf Therapeutics, a US-based biopharmaceutical company researching conditionally activated therapeutics in cancer treatment, announced on August 18, 2021 that they will collaborate with Merck (known as MSD outside of the U.S. and Canada) to evaluate their WTX-124 indukine program in conjunction with Merck’s anti-programmed death receptor-1 (PD-1 ) therapy KEYTRUDA (pembrolizumab).

WTX-124 is a systemically delivered, conditionally activated interleukin 2 (IL-2) indukine molecule engineered to minimize the severe toxicities observed with recombinant IL-2 therapy. It is intended to maximize clinical benefit both when administered as a monotherapy or in combination with checkpoint inhibitors in multiple tumor types.

Werewolf will conduct the clinical trial, which is designed to evaluate WTX-124 as both a monotherapy and in conjunction with Keytruda in patients with solid tumors. Werewolf is planning to submit an investigational new drug application in the first half of 2022, with the Phase I clinical trial set to begin promptly after approval.

“Werewolf Therapeutics is delighted to be partnering with Merck to study the combination of KEYTRUDA and WTX-124, ” said Randi Isaacs, chief medical officer of Werewolf Therapeutics, in a company press release. “The clinical benefit of targeting IL-2 as a treatment for cancer has long been established; however, its utility has been limited by challenging toxicities. We believe WTX-124 has the potential to enhance therapeutic options for cancer patients as a monotherapy and when combined with checkpoint inhibitors [such as] KEYTRUDA.”

The collaboration will focus on the interactions between WTX-124 indukine and KEYTRUDA (pembrolizumab).

Werewolf Therapeutics Announces Clinical Trial Collaboration with Merck

Scientists at the National Institutes of Health (NIH) have developed a new sample preparation method to detect SARS-Cov-2. Because this method bypasses extraction of the virus’ genetic RNA material, it simplifies sample purification and may reduce test time and costs.

Standard COVID-19 tests amplify viral RNA to detectable levels using quantitative reverse transcription polymerase chain reaction (RT-qPCR). RNA must be extracted from the sample to use this technique, which has put strain on manufacturers of RNA extraction kits.

NIH researchers tested a chelating agent (Chelex 100) made by lab supply company Bio-Rad to determine if it could be used to circumvent the traditional testing process. This agent preserves SARS-CoV-2 RNA in samples for detection through RT-qPCR.

Standard samples were tested using conventional RNA extraction and RT-qPCR, while those stored in the chelating agent were heated and then tested by RT-qPCR. NIH found that the new preparation method significantly increased the RNA yield available for testing relative to the standard method.

“We used nasopharyngeal and saliva samples with various virion concentrations to evaluate whether they could be used for direct RNA detection,” said Bin Guan, a fellow at the National Eye Institute's Ophthalmic Genomic Laboratory, in a press release from the organization. “The answer was yes, with markedly high sensitivity. Also, this preparation inactivated the virus, making it safer for lab personnel to handle positive samples.”

A new method developed by the NIH bypasses genetic RNA extraction, simplifying the testing process.

NIH Scientists Develop Faster COVID-19 Test

Merck (known as MSD outside the United States and Canada) announced in an August 13, 2021 press release that FDA approved Welireg for the treatment of adult patients with von Hippel-Lindau (VHL) disease who require therapy for associated renal cell carcinoma (RCC), central nervous system hemangioblastomas, or pancreatic neuroendocrine tumors, not requiring immediate surgery. Welireg is an oral hypoxia-inducible factor-2 alpha (HIF-2α) inhibitor and the first HIF-2α inhibitor therapy approved in the United States. It reduces transcription and expression of HIF-2α target genes associated with cellular proliferation, angiogenesis, and tumor growth. The recommended dose of Welireg is 120 mg once daily until disease progression or unacceptance toxicity.

FDA approval is based on results from the study 004 trial (NCT03401788), an open-label trial in 61 patients with VHL-associated RCC diagnosed based on a VHL germline alteration and with at least one measurable solid tumor localized to the kidney.

“The approval of WELIREG, which is based on data showing an overall response rate across three different types of VHL-associated tumors, addresses this significant unmet need by introducing a new option for physicians and their patients impacted by this disease,” said Eric Jonasch, principal investigator of study 004 and professor, department of Genitourinary medical oncology, division of cancer medicine, The University of Texas MD Anderson Cancer Center, in a press release.

FDA approves Merck’s Welireg for the treatment of adult patients with von Hippel-Lindau disease who require therapy for tumor growth.

FDA Approves First HIF-2α Inhibitor Therapy in US

The World Health Organization’s (WHO’s) solidarity plus trial, the next phase in its solidarity trial, will enroll hospitalized patients to test artesunate, imatinib, and infliximab in hospitalized COVID-19 patients, according to an August 11, 2021 press release. Artesunate, imatinib, and infliximab were selected for their potential to reduce the risk of death in hospitalized COVID-19 patients by an independent panel. These three drugs were donated for the trial by their manufacturers and are used for the following other indications:

 is used for diseases of the immune system, such as Crohn’s Disease and rheumatoid arthritis.

Previously, remdesivir, hydroxychloroquine, lopinavir, and interferon were evaluated by the trial and were found to have little or no effect on hospitalized patients with COVID-19.

The solidarity plus trial represents the largest global collaboration among WHO Member States and involves thousands of researchers in more than 600 hospitals in 52 countries. Multiple treatments are assessed at the same time using a single protocol. Thousands of patients are recruited to generate robust estimates on the effect a drug may have on mortality.

WHO’s solidarity plus trial will enroll hospitalized patients to test artesunate, imatinib, and infliximab in hospitalized COVID-19 patients.

WHO’s Solidarity Plus Trial to Assess Three Drugs for Hospitalized COVID-19 Patients

BlackBerry’s QNX real-time operating system (RTOS) may create cybersecurity vulnerabilities that introduce risks for certain medical devices and drug manufacturing equipment, according to FDA. To date, there aren’t confirmed adverse events related to these vulnerabilities.

In an alert (AA21-229A) by Cybersecurity and Infrastructure Security Agency (CISA) on August 17, 2021, CISA stated that BlackBerry publicly disclosed that its QNX RTOS is affected by a BadAlloc vulnerability—CVE-2021-22156—which is a collection of vulnerabilities affecting multiple RTOSs and supporting libraries. CVE-2021-22156 is an integer overflow vulnerability affecting the calloc function in the C runtime library of multiple BlackBerry QNX products and could be exploited by a remote attacker, causing a denial-of-service condition or execute arbitrary code on affected devices.

FDA stated that manufacturers are assessing which equipment or systems may be affected by the BlackBerry QNX cybersecurity vulnerability. In addition, manufacturers are evaluating the risk and developing mitigations, including deploying patches from BlackBerry.

Organizations impacted by the BlackBerry QNX cybersecurity vulnerabilities should contact FDA. Specifically, drug manufacturers regulated by the Center for Drug Evaluation and Research should contact: cdercybersecurity@fda.hhs.gov.

Cybersecurity and Infrastructure Security Agency (CISA)

BlackBerry’s QNX real-time operating system may create cybersecurity vulnerabilities, according to FDA.