Breakthrough Clinical Results
The FDA has granted full approval to Precigen's Papzimeos (zopapogene imadenovec-drba) for the treatment of adults with Recurrent Respiratory Papillomatosis (RRP). This is the first FDA-approved treatment for RRP, a rare disease characterized by the growth of tumors in the respiratory tract. Papzimeos is a non-replicating adenoviral vector-based immunotherapy designed to generate an immune response against papilloma cells. The approval marks a significant milestone for the RRP community, offering a non-surgical treatment option. Precigen also offers support services to patients for insurance navigation and financial assistance.
Key Highlights
- FDA approves Papzimeos (zopapogene imadenovec-drba) for adults with RRP.
- Papzimeos is the first FDA-approved treatment for RRP.
- It's a non-replicating adenoviral vector-based immunotherapy targeting the underlying cause of RRP.
- Precigen offers patient support services including insurance navigation and financial assistance.
Incidence and Prevalence
Latest Estimates of Incidence and Prevalence of Recurrent Respiratory Papillomatosis
Recurrent respiratory papillomatosis (RRP) is a disease characterized by the growth of wart-like neoplasms along the aerodigestive tract, caused by the human papillomavirus. The epidemiological data shows varying incidence rates across different populations and age groups.
Incidence Rates
Based on a 1996 survey of otolaryngologists in the United States, the incidence of RRP among children was estimated at 4.3 per 100,000, while for adults, it was 1.8 per 100,000.
More recent data from Korea (2002-2014) estimated the incidence of juvenile-onset RRP at 0.30 per 100,000 person-years, which was noted to be similar to rates reported in other countries.
Prevalence and Case Numbers
The 1996 US study projected 5,970 active cases among children (95% confidence interval: 3,465 to 8,474) and 9,015 active cases among adults (95% CI: 6,435 to 11,591) during the period from March 1993 to March 1994.
Age Distribution
The age distribution of RRP follows a bimodal curve, with the first peak around 5 years of age and the second occurring in adults in the third decade of life. This bimodal pattern has been consistently observed across studies.
In a Korean study of 123 children with RRP, the median age at diagnosis was 4.0 years (mean: 4.3), which aligns with the global pattern.
Viral Etiology
HPV types 6 and 11 are the primary aetiological agents of RRP. A 2021 study found that 71% of RRP cases were HPV positive, with HPV 6 being the most common genotype (71% of positive cases), followed by HPV 11 (26%).
In a US study (2015-2020), among 162 specimens tested, 96.9% had detectable HPV, and all of these had a vaccine-preventable type.
Transmission and Risk Factors
Transmission can occur from mother to child during birth, with one study showing a 57.14% concordance of HPV-DNA positivity between mothers and their neonates. Meta-analysis indicates that vertical transmission of HPV occurs in approximately 20% of cases.
In a US study of 215 children with juvenile-onset RRP, 88.8% were delivered vaginally and 64.2% were firstborn.
Impact of Vaccination
With increasing utilization of the 9-valent and quadrivalent HPV vaccine in Australia, there has been a significant decrease in the incidence of RRP. Preliminary data in the US shows a similar trend of decreased incidence after implementation of HPV vaccination.
Prognosis and Burden
Approximately 50% of children with juvenile-onset RRP experience recurrence and require repeated operations in adulthood. In a Chinese study, the mortality rate for juvenile-onset RRP was reported as 5%.
The disease imposes a substantial healthcare burden, with children requiring an estimated 16,597 surgical procedures at a cost of $109 million, and adults requiring 9,284 surgical procedures at a cost of $42 million according to the 1996 US study.
Drug used in other indications
Clinical Trials of Papzimeos for Non-RRP Indications
Based on a comprehensive review of available information, there is currently no documented evidence of clinical trials investigating zopapogene imadenovec-drba (Papzimeos) for indications other than Recurrent Respiratory Papillomatosis (RRP).
The gene therapy Papzimeos appears to be specifically developed for treating RRP, a rare disease caused by human papillomavirus (HPV) infection that results in recurrent growth of benign tumors in the respiratory tract.
At present, there are no clinical trials exploring the use of this therapeutic agent for: - Other HPV-related conditions - Non-respiratory papillomatosis - Any alternative indications beyond RRP
Consequently, there are no intervention models to report regarding trials for non-RRP indications, as such trials have not been established or documented in the available clinical research literature.
As gene therapy approaches continue to evolve, future research may potentially expand the application of zopapogene imadenovec-drba to other conditions, particularly those with similar pathophysiological mechanisms involving HPV infection. However, at this time, RRP remains the sole focus of clinical investigation for this specific therapeutic agent.
Healthcare providers and patients interested in treatment options for conditions other than RRP would need to explore alternative therapeutic approaches currently approved or under investigation for those specific indications.
Economic Burden
Economic Burden of Treating Recurrent Respiratory Papillomatosis in USA and Europe
Recurrent respiratory papillomatosis (RRP) is a benign condition caused by the human papillomavirus (HPV), particularly subtypes 6 and 11, but imposes a significant financial burden on healthcare systems worldwide.
United States
The most recent economic cost analysis for RRP in the United States was published in 2023, which updated previous estimates to account for HPV vaccination impact, reduced cervical cancer screening frequency, and new data on HPV-attributable cancer treatment costs. This study estimated that RRP accounts for less than 2% of the total $9.01 billion annual direct medical cost of HPV in the United States over the period 2014-2018 (in 2020 U.S. dollars).
For comparison, the annual direct medical cost attributable to HPV in the United States over the period 2004-2007 was previously estimated at $9.36 billion in 2012 (updated to 2020 dollars). The 2023 updated estimate is slightly lower than the previous estimate but would have been substantially lower had they not incorporated more recent, higher cancer treatment costs.
A 2007 study found that performing surgery with the pulsed dye laser (PDL) in the office instead of the operating room resulted in average cost savings of more than $5,000 per case. However, current reimbursement rates did not cover the cost of performing unsedated office-based laryngeal laser surgery (UOLS).
Europe
In Italy (2018), the total annual direct costs for nine major HPV-related diseases were €542.7 million (range €346.7-€782.0 million). The fraction attributable to the HPV9 genotypes was €329.5 million, accounting for 61% of the total annual burden of HPV-related diseases.
In the UK, a 2017 study found that the direct measurable cost to NHS Greater Glasgow and Clyde for just 14 patients with active RRP between 2013 and 2014 amounted to £107,478. A 2010 UK study estimated that RRP costs in the region of £4 million annually despite RRP being comparatively rare, whereas HPV-related genital tract disease costs around £31 million per annum.
A 2014 European study across seven countries (Denmark, France, Germany, Greece, The Netherlands, Portugal, and the UK) found that non-cervical cancers attributable to HPV impose a substantial economic burden in Europe, with the burden being greater in men than in women.
In Belgium (2009), the management costs of RRP were not included in their analysis of HPV-related disease costs, suggesting that the total economic burden is likely underestimated.
Disease Burden Factors
The burden for patients and healthcare systems is significant given the recurrent nature of the disease. Patients often require many surgical procedures over years to control it, with frequent surgical debridement of disease. As of 2020, there were no approved systemic adjuvant therapies. The natural history of relapse and remission means patients may require healthcare input over several years, contributing to the ongoing economic burden.