Indian Regulators Authorize for Emergency Use Needle-Free DNA Plasmid COVID-19 Vaccine for Young People 12-18
An Indian biotech received an Emergency Use Authorization (EUA) from the Drug Controller General of India (DCGI) for what they have declared as the world’s first world’s first Plasmid DNA Vaccine for COVID-19. Developed by Zydus Cadila, the biotech declared in a press release that ZyCoV-D is a three dose vaccine which will be administered first on day zero, day 28th and then on the 56th day. With this approval, India now has its first COVID-19 vaccine for the adolescents in the 12-18 age group, besides the adult population. Of interest, the ZyCoV-D vaccine is delivered via needle-free method, using what’s called The PharmaJet® a needle free applicator, which ensures painless intradermal vaccine delivery. Zydus Cadila stated they would produce 100-120 million doses of the novel product annually.
The Investigational Product
ZyCoV-D is a plasmid DNA vaccine that triggers the spike protein of the SARS-CoV-2 virus and elicits an immune response mediated by the cellular and humoral arms of the human immune system reports the company. The company lists some facts about the investigational product including: 1) ZyCoV-D is an intradermal vaccine, which will be administered in three doses; 2) It will be applied using The PharmaJet® needle free system, Tropis®, which can also lead to a significant reduction in any kind of side effects; 3) ZyCoV-D is stored at 2-8 degree C but has shown good stability at temperatures of 25 degree C for at least three months. The thermostability of the vaccine will help in easy transportation and storage of the vaccine and reduce any cold chain breakdown challenges leading to vaccine wastage; 4) The plasmid DNA platform provides ease of manufacturing with minimal biosafety requirements (BSL-1); 5) Also being a Plasmid DNA vaccine, ZyCoV-D doesn’t have any problem associated with vector based immunity; 6) The Plasmid DNA platform also allows generating new constructs quickly to deal with mutations in the virus, such as those already occurring; 7) The results of the Phase I part of the Phase I/II clinical trial have already been published in the EClinical Medicine Journal of Lancet.
For more on the PharmaJet® needle free system, Tropis we refer to the manufacturers website.
Novel Vaccine–Flexible
Claiming that this is the first time that a technologically advanced vaccine has been successfully developed on the Plasmid DNA platform for human use, the company posits another major benefit targeting SARS-CoV-2. That is, it’s purpose-designed to deal with a rapidly evolving virus, mutations ongoing. That’s because of what they call their “rapid plug and play technology” that supports and facilitates updates to the product specifically for variants.
Vaccination Young People
By using the needle-free technology the company seeks to be at the forefront of offering vaccine products to the age group 12-18.
Why a DNA-based vaccine”
Zydus Cadila suggests that DNA vaccines trigger both humoral and cellular arms of the adaptive immune system. That is a more comprehensive, value-added form of antigen-specific immunotherapy and purportedly “safe” and “stable” while easy to produce.
Collaborations, Partnerships and Public Backing
The company benefited from significant collaboration and government support in the research and development and clinical development processes, from the National BioPharma Mission and BIRAC to India’s Department of Biotechnology, the National Institute of Virology, India Council of Medical research and PharmaJet.®
How do Plasmid NDA vaccines compare to mRNA?
Academia, government research institutes and biotech ventures have been working on both approaches for nearly three decades, interest in mRNA accelerated due to breakthroughs in the veterinary vaccine markets. Over the years intensive efforts have focused on boosting potency by direct engineering of the mRNA or plasmid DNA experimental candidates or via adjuvants and immunomodulators or other delivery systems or formulations writes Margaret A Liu, in “A Comparison of Plasmid DNA and mRNA as Vaccine Technologies.” Ms. Liu is a Board Chair, International Society of Vaccines.
Liu notes some of the greater risks, and upside with mRNA-based vaccines declaring “The greater inherent inflammatory nature of the mRNA vaccines is discussed for both its potential immunological utility for vaccines and for the potential toxicity.” This piece was authored in 2019 prior to the pandemic but nonetheless offers an important overview.
The Company
An Indian multinational, Zydus Cadila primarily is known for its production of generic drugs and is ranked 100th in the Fortune India 500 list in 2020. The company actually goes back to 1952 to its founding by a former lecturer in pharmacy, Ramanbhai Patel (deceased in 2001) and industrialist Indravadan Modi (deceased 2012) who is known as “the medicine man” in India.
Historical Intrigue
The company’s original founders, the Patel’s and the Modi families, split in 1995. As a consequence the Modi group formed a new company called Cadila Pharmaceuticals Ltd., while Cadila Healthcare Ltd. became the Patel’s family holding. The latter went public on the Bombay Stock Exchange in 2000 (532321). Thereafter Cadila Healthcare went on to make a handful of acquisitions including Zydus Healthcare Brasil Ltda.
The company was one of the largest pharmaceutical companies in India by early 2000s but by 2005 other companies emerged and the company’s ranking waned. Pankaj R. Patel, serves as the Chairman.
Financials
With 25,000 employees the company reports turnover of $2.1 billion with profits of $300 million.
Zydus Cadila secured authorization to start clinical trials testing ZyCoV-D from India’s DCGI last July, 2020. They also inked a deal with Gilead to produce remdesivir in India for the COVID-19 market as reported in the Business Standard.
Price Fixing Scandal & U.S. Lawsuit
TrialSite reported in 2019 that over 40 state Attorney Generals in the United States filed a lawsuit accusing dozens of the largest generic producers, including Zydus Cadila, of conspiring to inflate drug prices by over 1000% in some cases.
Filed in the United District Court for the District of Connecticut, the large, complex and ongoing suit is led by Connecticut Attorney General William Tong. In fact Tong recently filed a new complaint along with 51 other states and territories (the third lawsuit) originating from the ongoing antitrust investigation we reported on. The original lawsuit centers on a vast, widespread conspiracy by generic drug makers (Zydus included) to artificially inflate and manipulate drug prices.