On October 30, the FDA approved the first plasmid DNA-based immunotherapy from Inovio Pharmaceuticals. The medication, Voceryq, treats recurrent respiratory papillomatosis (RRP), in which small wart-like tumors develop in the respiratory tract as a result of chronic infection with human papillomavirus (HPV). RRP has traditionally required numerous surgeries that do not act as a cure; thus Voceryq offers patients the first therapy that targets the mechanistic cause of disease.
Voceryq also injects invigorated enthusiasm for the field of DNA-based medicines as a whole.
“Having one therapeutic approved really lays the foundation for others to advance rapidly through the clinical investigation pipeline to approval. It always helps to have a ‘first-in-class’ lead the way,” Mary “Nora” Disis, Professor of Hematology and Oncology at the University of Washington, told DDN.
The manufacturing market for plasmid DNA is already massive, driven by demand for its role in gene and cell therapies and mRNA vaccines. Currently valued at $2.8 billion, the market is expected to quickly rise to $9.3 billion by 2033.
But the new approval situates plasmid DNA in a new realm — as a therapy in its own right.
In the FDA press release, FDA Director of the Center for Biologics Evaluation and Research Karim Mikhail said, “Today’s approval represents a meaningful scientific breakthrough: a plasmid DNA-based immunotherapy that harnesses the body’s own immune system to fight the underlying cause of RRP.”
Why Voceryq received accelerated approval
The accelerated approval of Voceryq followed early days that didn’t look promising. After Inovio’s Biologics License Application (BLA) was submitted, the company said in a March statement that the FDA emphasized a possible review issue due to inadequate information provided to justify the accelerated approval pathway. Yet, a PDUFA was set for October 30, and during that time the FDA experienced several staffing transitions, including many high-level position changes after former FDA Commissioner Martin Makary was replaced with Kyle Diamantas.
“This was a very aggressive approval timeline and as an accelerated approval, more work will need to be done for permanent approval of Voceryq,” said Disis. She explained that the FDA needed to take into account that RRP is a rare disease with very few treatment options. “I applaud the FDA for considering these issues when deciding on accelerated approvals. The clinical trial that led to the Voceryq being used for recurrent respiratory papillomatosis demonstrated only low grade adverse events and evidence of efficacy. This gives patients with this rare condition more options,” she said.
Voceryq works by delivering two plasmids — one that houses the genetic instructions for HPV proteins, and the other the IL-12 cytokine — to coax the immune system to go after cells infected by HPV types 6 and 11 that cause RRP. It’s delivered intramuscularly via Inovio’s CELLECTRA 5PSP Device that enables entry into cell membranes via electroporation.
The approval came based on results from a Phase 1/2 open-label multi-center trial in 32 adults with RRP, which showed that 27 percent of patients achieved a complete response requiring no further surgeries after 12 months with the treatment.
In the company press release, Inovio stated plans to make Voceryq available to order and ship in about 60 days and a full commercial launch in the first quarter next year.
“With the approval of Voceryq, we believe our DNA medicine platform has the potential to transform the treatment paradigm for RRP by offering a patient-centric treatment option,” said Jacqueline Shea, President and CEO of Inovio, in the statement. “We look forward to delivering VOCERYQ to the RRP community and believe it has the potential to become a new standard of care for this devastating disease."
The future of DNA-based medicines
Voceryq’s approval represents the first approved DNA medicine — and establishes Inovio’s platform as a major player. The company already has several other candidates in clinical trials to treat wide-ranging conditions including cervical dysplasia, head and neck cancer, anal dysplasia in HIV, and Ebola.
Other plasmid DNA-based therapies under study may not be far behind. Disis is leading a Phase 2 trial of STEMVAC, a plasmid DNA cancer vaccine, to treat metastatic triple-negative breast cancer. So far, she said that Phase 1 data showed that STEMVAC led to immunity against five cancer-associated proteins in some patients, and that it is well tolerated.
The vaccine is also in trials to treat hormone receptor positive breast cancer and non-small cell lung cancer. “We have a very aggressive development plan for STEMVAC as it could potentially have activity across many different types of tumors,” said Disis.
Disis noted that after studying many delivery platforms, her team chose the plasmid DNA approach because it’s easy to manufacture without needing to be kept at extremely low temperatures, it’s simple to inject intradermally, and it leads to high levels of immunity with only low-grade adverse events.
“Approval of Voceryq validates the safety and efficacy of DNA-based approaches and, hopefully, will result in many more DNA based immunotherapeutics like STEMVAC, being available for patients in the near future,” said Disis.
