Coronavirus Vaccine as Biopharmaceutical Product

As Chinese Coronavirus Spreads, Biopharma and Governments Rush to Develop Vaccines
China’s National Health Commission stated today that the coronavirus has infected 5,974 individuals, resulting in 132 deaths and 103 people being cured. This has passed the number of patients who were infected with SARS, or severe acute respiratory syndrome, in 2003. As more and more cases are being diagnosed around the world, including in the U.S. and Canada, government officials and biopharma companies are fast-tracking vaccine development.

A number of biopharma companies have indicated they plan to focus on developing a vaccine as soon as possible. One is Moderna, which has mRNA vaccine technology, and is working with NIH/NIAID/VRC on a potential vaccine

PEGylated Biopharmaceuticals: Current Experience and Considerations for Nonclinical Development

The development of new PEGylated biopharmaceuticals has triggered the need for the formulation of a strategy to address the impact of PEG-related cytoplasmic vacuolation when seen in nonclinical toxicology studies. It should be considered that histologically observed cellular vacuolation alone without other changes in the surrounding cells (e.g., no cellular distortion, necrosis, or inflammation) should not by default be considered adverse as the tissue/cellular vacuolation can be adaptive and not a sign of a toxic response (see also Rudmann et al. 2013).
Other factors such as the type of cell affected as well as the margins between observations of vacuolation in animal studies compared to clinical dose, dosing frequency, and duration of treatment, and the intended indication and target population should be considered when determination the risk/ benefit assessment of PEGylated biopharmaceuticals. The determination of a NOAEL as well as its application’s may be influenced by the underlying definition of adversity and the data available.

Development and Clinical Translation of Approved Gene Therapy Products for Genetic Disorders

The field of gene therapy is striving more than ever to define a path to the clinic and the market. Twenty gene therapy products have already been approved and over two thousand human gene therapy clinical trials have been reported worldwide. These advances raise great hope to treat devastating rare and inherited diseases as well as incurable illnesses. Understandings of the precise pathomechanisms of diseases as well as the development of efficient and specific gene targeting and delivery tools are revolutionizing the global market. Currently, human cancers and monogenic disorders are indications number one. The elevated prevalence of genetic disorders and cancers, clear gene manipulation guidelines and increasing financial support for gene therapy in clinical trials are major trends. Gene therapy is presently starting to become commercially profitable as a number of gene and cell-based gene therapy products have entered the market and the clinic. This article reviews the history and development of twenty approved human gene and cell-based gene therapy products that have been approved up-to-now in clinic and markets of mainly North America, Europe and Asia.
In medicine, gene therapy is defined as therapeutic strategy that transfers DNA to a patient’s cells to correct a defective gene or a gene product in order to treat diseases that are not curable with conventional drugs. Direct in vivo administration of manipulated viral vehicle for gene delivery and ex vivo genetically engineered stem cells are the two principal approaches in advanced clinical gene therapy.

Human Gene Therapy Products

Vitravene (Fomivirsen)

Vitravene, also called as Fomivirsen is an antisense oligonucleotide (ASO) designed as a therapeutic strategy for cytomegalovirus (CMV) retinitis in HIV-positive patients who have not an option for CMV retinitis treatment.

Gendicine (rAd-p53)

Gendicine gene therapy drug is harboring Tp53 gene which has been developed to treat head and neck squamous cell carcinoma (HNSCC). This recombinant adenovirus was developed by Shenzhen SiBionoGeneTech and was approved by China Food and Drug Administration (CFDA) on October 16, 2003; and found its way to the commercial market in 2004.

Macugen (Pegaptanib)

Pegaptanib was developed by Eyetech Pharmaceuticals and PfizerInc with brand name of Macugenis. It is a polynucleotide aptamer targeting vascular endothelial growth factor (VEGF165 isoform) for neovascular age-related macular degeneration (AMD) treatment.

Oncorine (rAd5-H101)

As the first oncolytic virus approved by CFDA, recombinant human adenovirus type 5 (rAd5-H101) was commercially marketed under the brand name of Oncorine in November 2005 and was manufactured by Shanghai Sunway Biotech.

Rexin-G (Mx-dnG1)

Rexin-G is a retroviral vehicle harboring a cytocidal cyclin G1 construct and is considered the world’s first tumor targeting injectable gene therapy vector approved by FDA for metastatic pancreatic cancer.

Neovasculgen (Pl-VEGF165)

In 2010, Human Stem Cell Institute of Russia developed Neovasculgen (PI-VEGF165), a plasmid DNA encoding VEGF 165 under the control of a CMV promoter for treatment of atherosclerotic Peripheral Arterial Disease (PAD).

Invossa (TissueGene-C)

Invossa (TissueGene-C) has completed phase III trials in the USA and attained marketing approval in Korea by KolonTissueGene as a first-in-class cell mediated gene therapy strategy for the treatment of symptomatic and persistent knee osteoarthritis (OA). It contains 3:1 mixture ratio of non-transformed and retrovirally transduced allogenic chondrocytes that upregulate transforming growth factor β1 (TGF β1).

Recent advances in understanding molecular mechanism of human diseases and treatment are boosting the global gene therapy market. This market is categorized into cancers, neurological diseases, rare genetic diseases, cardiovascular disorders, and infectious diseases. Cancers and monogenic diseases had the highest market share in recent years respectively.

Big pharma backed away from brain drugs

Neuroscience still receives healthy levels of early investment, though. It attracted $1.5 billion from venture capitalists in 2018, putting it second only to cancer and suggesting these financiers expect payoffs in the not-too-distant future, perhaps through a big pharma buyout.
Their bet may be well placed too, as industry watchers foresee big pharma mounting a return to neuroscience in the next few years, lured by emerging treatments for epilepsy, mood disorders and genetic diseases of the CNS, or central nervous system.
Drugmaking technologies may also be more valuable than the specific disease target. Ted Dawson, director of the Institute for Cell Engineering at Johns Hopkins Medicine, says he’s seen “an enormous amount of excitement” around antisense therapies that regulate gene expression. Ionis’ business revolves around the antisense platform responsible for developing Biogen’s muscular atrophy drug, while Alnylam Pharmaceuticals has a similar platform that’s at the center of a $1 billion CNS research pact with Regeneron.

Pfizer lays out gene therapy aspirations

Pfizer aims to be the third big pharma with a significant presence in gene therapy. Its plans to initiate this year three Phase 3 trials targeting mutation-driven blood and muscular diseases would make it a large player in this cutting-edge area of medicine.
The difference between Pfizer and its Swiss rivals Novartis and Roche is that its treatments for muscular dystrophy and hemophilia do not look like they will be the first to market. With hopes that gene therapy could be a one-and-done treatment, arriving second could put Pfizer at a disadvantage if eager patients rush for curative therapies.