Recently, Precigen announced that it had received FDA approval of its immunotherapy PAPZIMEOS for the treatment of adults with recurrent respiratory papillomatosis (RRP). Besides the company being able to generate sales from this approved therapy, it is even more crucial due to the fact that it made history in being the first and only FDA-approved drug to treat these patients. This is an important point to note because this rare respiratory disorder was an unmet medical need. Before this landmark U.S. approval of PAPZIMEOS, patients had to undergo repeat surgeries due to the recurring nature of this disorder. Either surgery alone or adjuvant antiviral medications like interferon and/or cidofovir could help somewhat.
RRP is characterized as the growth of wart-like tumors [papillomas] in the respiratory tract. This is not the type of disease where these growths can be ignored. The main area where RRP occurs is in the voice box but can also grow around surrounding areas as well. An issue with the voice box (larynx) is only one problem that these patients have to contend with. They even have to worry about having the area clogged up to the point where they can’t breathe effectively either. As you can see, even though the papillomas that form are benign (non-cancerous) growths, they still need to be taken care of promptly because of the issues I just described.
What makes this approval all that much more special, besides the fact that these patients finally have a treatment option that treats the underlying cause of RRP and not just the symptoms it brings, would be the surprise it obtained from the FDA based on this approval. The thing is that the goal was for Precigen to seek accelerated approval for PAPZIMEOS, which was possible thanks to a rolling Biologics License Application (BLA) submission in December of 2024. However, instead of the FDA only granting the therapy with accelerated approval, it just decided to grant full approval instead. This is significant because typically once a drug is given accelerated approval, it must be followed with a confirmatory study thereafter. With the FDA just deciding to grant full approval instead, this means the company won’t need to run a confirmatory trial. This will not only conserve its cash, but it also means no risk of the drug being removed from the market.
The reason why is because if a confirmatory trial fails to show the drug achieves clinical benefit, then the FDA has the option of pulling the drug off of the market. In this case, this risk has now been removed due to the fact that full approval was granted for PAPZIMEOS. RRP is caused by the human papillomavirus (HPV). More specifically, it is the HPV6 and HPV11 subtypes. The good news is that these subtypes of HPV don’t typically cause cancer, but as noted above, they are responsible for recurring benign growths. The science of PAPZIMEOS is quite interesting because there is the use of T-cells that enter and kill papillomas in patients with RRP. This phenomenon occurs because of vector delivery whereby host cells, which interact with tumor cells, are presented with antigens (selected regions of HPV 6 and HPV 11). The purpose of this is to elicit a T-cell-mediated immune response against these wart-like growths seen in these patients.
All of this is possible thanks to several components of the company’s AdenoVerse platform. First and foremost, it offers up the ever-important off-the-shelf nature of immunotherapy (pre-manufactured use of healthy donor cells). Other features are larger payload capacity, the ability to repeat administration as necessary, and the creation of a durable antigen-specific response. These last three I just mentioned are possible thanks to the AdenoVerse technology using what are known as gorilla adenovectors. These are important because not only do they provide these functions I just described, but they also allow the immunotherapy to be replication defective. With an inability for the vector to replicate, it allows for efficient delivery of the payload while at the same time reducing adverse events (AEs) that might be observed in therapies that deploy replicating vectors.
This is a devastating disease to deal with, and the unmet medical need nature described deals with the fact that these patients require a lot of surgery. For instance, the single-arm, open-label study that allowed the company to receive full FDA approval of PAPZIMEOS recruited patients who had about three surgeries or more per year. These patients were given four subcutaneous injections of this immunotherapy over a 12-week period, following a surgical procedure. In a pivotal cohort of this particular trial with 35 patients, about 18 of them (51.4%) required no surgical intervention in the 12 months following this treatment plan.
Furthermore, the pipeline that Precigen has underscores the ability to expand the use of its AdenoVerse platform. Another candidate it is working on is PRGN-2009, which uses this specific platform, along with its UltraVector platform. The end-game goal is to develop HPV 16/18 antigens in a gorilla adenovector. With this candidate, it can go after HPV-associated cancers. It is currently running two phase 2 studies with the National Cancer Institute to target patients with recurrent/metastatic cervical cancer and newly diagnosed HPV-associated oropharyngeal cancer.