Pharmaceutical Technology Editors

Aria Pharmaceuticals, a pharmaceutical company specializing in small-molecule drugs, announced that it has filed for six provisional patents with the United States Patent and Trademark Office (USPTO) on Aug. 30, 2022. The patents concern the company’s lead candidates in its lupus, idiopathic pulmonary fibrosis (IPF), and chronic kidney disease (CKD) research programs.

According to a company press release, Aria developed two new chemical entities (NCEs) in each disease category, which account for the six new patent applications. The company has narrowed down the six NCEs to three lead candidates in each disease category using its Symphony drug discovery platform. The three lead candidates consist of:

TXR-711, an investigational treatment for lupus. This treatment inhibits targeted key signaling pathways with the goal of decreasing antibody production and cytokine expression; it is also designed to reduce inflammation through multiple pathways and processes.

TXR-1002, an investigational treatment for IPF. This treatment is designed to inhibit myofibroblast proliferation, collagen, transforming growth factor beta (TGF-β), fibrosis, and inflammation.

TXR-1210, an investigational treatment for CKD. By inhibitng pyroptosis and regulating interleukin-1 activity, TXR-1210 is designed to regulate renal inflammation and fibrosis, decrease the release of proinflammatory cytokines, and inhibit TGF-β expression.

“These filings represent significant development milestones for Aria and are in line with our strategic focus on moving our proprietary pipeline forward,” said Andrew A. Radin, CEO, Aria Pharmaceuticals, in the release. “By analyzing multiple heterogeneous data types in one process, our drug discovery platform Symphony is proving capable of discovering novel therapies where we have high confidence in their viability as novel treatments.”

“We are excited and confident in the data across all of our early-stage candidates,” said Anjali Pandey, senior vice-president of Nonclinical R&D and Chemistry, Aria, in the release. “This achievement takes us closer to our goal of moving novel treatments into clinical research, and we’re ready for the next steps needed for clinical success.”

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The patent applications are for programs concerning lupus, idiopathic pulmonary fibrosis, and chronic kidney disease.

Aria Pharmaceuticals Files Applications for Six Provisional Patents

Hovione announced on September 6, 2022 that it has expanded its continuous manufacturing offering and services with a new manufacturing line, team, and facility.

The new continuous manufacturing facility is coming online at the Loures site in Portugal. Hovione is also strengthening its capabilities by establishing an experienced, multi-disciplinary global team in continuous tableting. The company is also upgrading its labs with the tools required to support the drug product lifecycle.

Hovione is offering customers a commercial continuous tableting platform designed to support key control needs and deliver on operational excellence, mechanistic modeling, and appropriate process analytical technology. The company’s quality system is designed to support the release of continuous tableting products through automated in-process controls, deployment of real-time release, and compliant digital infrastructure.

“Hovione has been historically focused on innovative technologies that benefit our customers and patients. With this investment in continuous tableting, our customers can rely on our support to bring much needed medicines to the market as fast as possible with the highest quality and manufacturing standards,” said Jean-Luc Herbeaux, CEO of Hovione, in a company press release. “We are investing to accelerate the adoption of this technology as we continue to innovate and enhance our offering around our areas of expertise.”

Hovione has expanded its drug product offering with a new manufacturing line dedicated to continuous tableting.

Hovione Expands its Continuous Manufacturing Offering and Services

Novo Nordisk and Forma Therapeutics announced on Sep. 1, 2022 that Novo Nordisk would be acquiring Forma Therapeutics for approximately $1.1 billion. Novo Nordisk’s acquisition of Forma grants them access to the company’s portfolio of sickle cell disease (SCD) and rare blood medicines, including its lead development candidate, etavopivat. The transaction is expected to close in the fourth quarter of 2022.

Etavopivat is an investigational oral, once-daily, selective pyruvate kinase-R (PKR) activator that is being developed to improve anemia and red blood cell health in people with SCD. According to a company press release, it activates the red blood cell’s natural PKR activity to decrease levels of the metabolite 2,3-diphosphoglyceric acid; this is designed to allow sickle hemoglobin to hold on to oxygen longer, resulting in decreased polymerization, hemolysis, and sickling. It is currently being evaluated in a global Phase II/III trial in patients with SCD and a Phase II trial in patients with transfusion-dependent SCD and another inherited hemoglobinopathy called thalassemia.

“Novo Nordisk has worked for more than 40 years to develop and deliver transformative medicines to patients around the world with rare and devastating diseases. By adding Forma’s differentiated approach to address unmet needs for patients, we are taking a step forward in enhancing our sickle cell disease pipeline,” said Ludovic Helfgott, executive vice-president and head of rare disease, Novo Nordisk, in a company press release. “We have an ambition to build a leading portfolio with standalone and combination treatments to tackle the complications and underlying causes of sickle cell disease.”

“Today’s announcement is an exciting milestone that accelerates Forma’s purpose to transform the lives of patients with sickle cell disease and other serious hematological diseases,” said Frank D. Lee, president and CEO, Forma Therapeutics, in the release. “Novo Nordisk will partner closely with the sickle cell community to amplify our impact for patients around the world who urgently need new treatment options. We look forward to working together with Novo Nordisk to serve as a trusted partner to our communities and to advance innovation, access, and health equity for patients.”

Novo Nordisk’s $1.1 billion acquisition of Forma Therapeutics is intended to expand its sickle cell and rare blood disorder portfolio.

Novo Nordisk to Acquire Forma Therapeutics for $1.1 Billion

FDA amended the emergency use authorizations of the Moderna and Pfizer-BioNTech COVID-19 vaccines on Aug. 31, 2022 to authorize bivalent formulations of the vaccines for use as a single booster dose two months after a primary or booster vaccination. The updated boosters contain both the original strain of SARS-CoV-2 and the other one in common between the BA.4 and BA.5 lineages of the omicron variant. The Moderna vaccine is authorized for individuals aged 18 and older; the Pfizer-BioNTech vaccine for individuals aged 12 and older.

“The COVID-19 vaccines, including boosters, continue to save countless lives and prevent the most serious outcomes (hospitalization and death) of COVID-19,” said Robert M. Califf, Commissioner, FDA, in an agency press release. “As we head into fall and begin to spend more time indoors, we strongly encourage anyone who is eligible to consider receiving a booster dose with a bivalent COVID-19 vaccine to provide better protection against currently circulating variants.”

According to the press release, these approvals were based on positive findings from separate clinical trials. Both trials found the immune response against BA.1 was stronger among participants who received the bivalent vaccine than those who had received the monovalent vaccine.

“The FDA has extensive experience with strain changes for annual influenza vaccines. We are confident in the evidence supporting these authorizations,” said Peter Marks, director of the Center for Biologics Evaluation and Research, FDA, in the press release. “The public can be assured that a great deal of care has been taken by the FDA to ensure that these bivalent COVID-19 vaccines meet our rigorous safety, effectiveness and manufacturing quality standards for emergency use authorization.”

FDA has issued an emergency use authorization for both the Pfizer-BioNTech and Moderna bivalent COVID-19 boosters.

FDA Authorizes Bivalent COVID-19 Boosters

Bio-Rad Laboratories recently introduced a range of type 1 antibodies that are designed to inhibit the binding of evolcumab to its target, human proprotein convertase subtilisin/kexin type 9 (PCSK9). These sequence-defined, recombinant antibodies are intended to develop highly selective and sensitive pharmacokinetic (PK) and anti-drug antibody (ADA) assays for evolcumab and its biosimilars.

Evolocumab is a monoclonal antibody (mAb) that has been used for the treatment of hyperlipidemia, or elevated levels of cholesterol and other lipoproteins. It binds to PCSK9, which, according to an Aug. 25, 2022 company press release, has been shown to play a key role in the regulation of cholesterol levels. By preventing the interaction between PCSK9 and low-density lipoprotein receptors, it intends to reduce circulating cholesterol and other lipoproteins.

This range of five anti-evolocumab antibodies includes fully human immunoglobulin G1 clones and recombinant human combinatorial antibody libraries antibodies with SpyTag (a technology for irreversible conjugation of recombinant proteins) technology incorporated into their heavy chain; this is designed to enable site-directed conjugation or fast-switching to a bivalent Fab or a full-length Ig-like format within an hour. The antibodies can also be used to develop PK bridging, enzyme-linked immunoassays to measure free drug or as a surrogate positive control or reference standard in an ADA assay.

"Bio-Rad's range of ready-made and well-characterized anti-idiotypic antibodies keeps growing, offering researchers enhanced flexibility for the development of custom bioanalytical drug assays against a wide range of marketed biologic drugs,' said Hilary Latham, marketing director, Life Science Group, Bio-Rad, in the press release. "Generated under stringent quality control for batch-to-batch consistency, these antibodies can produce translatable and reproducible results, ensuring assay reliability."

Bio-Rad’s new antibodies are designed to develop highly selective pharmacokinetic (PK) and anti-drug antibody (ADA) assays for evolocumab and its biosimilars.

Bio-Rad Launches Anti-Evolocumab Antibodies

Roche recently announced the launch of its first digital polymerase chain reaction (PCR) system, the Digital LightCycler System (DLS). The DLS is designed to detect disease and accurately quantify trace amounts of specific DNA and RNA targets that are not typically detectable by conventional PCR methods.

According to an Aug. 23, 2022 press release, the DLS will allow clinical research to divide DNA and RNA from a clinical sample into up to 100,000 microscopic individual reactions. This provides opportunities for high precision analysis, including identifying ultra-rare targets or accurately quantifying how much of the target DNA/RNA there is at a molecular level.

"Understanding the hidden characteristics of serious diseases is fundamental for ensuring that the most effective treatment is selected for each patient," said Thomas Schinecker, CEO, Roche Diagnostics, in the press release. “The Digital LightCycler System will support clinical researchers and laboratories in identifying rare and emerging disease mutations. This can be instrumental in early diagnosis and therapy decisions."

Roche’s Digital LightCycler System is designed to aid in diagnostics for cancer, genetic disease, and infection.