Rare Pulmonology News

Spotlight On

Recurrent respiratory papillomatosis (RRP)

Recurrent respiratory papillomatosis (RRP) is a rare viral disease where tumors (papillomas) grow in the respiratory tract

Prevalence

1-9 / 100,000

3,310 - 29,790

US Estimated

1-9 / 100,000

5,135 - 46,215

Europe Estimated

Age of Onset

ageofonset-childhood.svg

ICD-10

-

Inheritance

Autosomal dominant

no.svg

Autosomal recessive

no.svg

Mitochondrial/Multigenic

no.svg

X-linked dominant

no.svg

X-linked recessive

no.svg

5 Facts you should know

FACT

1

The tumors are caused by human papillomavirus (HPV) infection of the throat.

FACT

2

The tumors may lead to narrowing of the airway, which may cause vocal changes or airway obstruction.

FACT

3

There are two types of RRP - juvenile-onset and adult-onset.

FACT

4

They may vary in size and grow very quickly, and may grow back even when removed.

FACT

5

These tumors rarely become cancerous, but can cause long-term airway and voice complications.

Interest Over Time

Google searches

Recurrent respiratory papillomatosis (RRP)

Recurrent respiratory papillomatosis

RRP; Juvenile laryngeal papilloma; Laryngeal papilloma, recurrent; Juvenile-onset recurrent respiratory papillomatosis (type); JORRP (type); Adult-onset recurrent respiratory papillomatosis (type); AORRP

What’s your rare IQ?

Recurrent respiratory papillomatosis is caused by which two HPV viruses?

Test Yourself

Common Signs & Symptoms

Dysphonia

Voice hoarseness

Benign tumors in the airway

(non-cancerous)

Dyspnea

Shortness of breath

Chronic cough

Respiratory distress

Breathing difficulties
Difficulty breathing

Increased proportion of transitional B cells

Failure to thrive

Faltering weight
Weight faltering

Hemoptysis

Coughing up blood

Current treatments

There is no cure for recurrent respiratory papillomatosis (RRP). Surgery is the primary method for removing tumors to keep the airway open and maintain the voice.[2][3] Because the tumors often grow back, it is common for affected individuals to require repeat surgery. In the most extreme cases where tumor growth is aggressive, a tracheostomy may be performed.[2][3]

About 20% of people with RRP will need adjuvant therapies—therapies that are used in addition to surgery. These include antiviral and anti-tumor medications. The HPV vaccine helps to prevent infection and spread of the virus. There is some evidence that the HPV vaccine may reduce the severity of symptoms in people with RRP.[5]

Specialists who may be involved in the care of someone with RRP include:

    • Otolaryngologist (ENT doctor)
    • Pulmonologist (lung specialist)
    • Surgeon
    • Infectious disease specialist

Top clinical studies

TitleDescriptionPhasesStatusInterventionsMore Information
INO-3107 With Electroporation (EP) in Participants With HPV-6- and/or HPV-11-Associated Recurrent Respiratory Papillomatosis (RRP) This is a Phase 1/2 open-label, multicenter trial to evaluate the safety, tolerability, immunogenicity, and efficacy of INO-3107 in subjects with HPV-6 and/or HPV-11-associated recurrent respiratory papillomatosis (RRP). The trial population will include participants who have been diagnosed with either Juvenile-Onset RRP (J-O RRP) as defined by age at first diagnosis <12 years or with Adult- Onset RRP (A-O RRP) as defined by age at first diagnosis ≥12 years. A safety run-in will be performed with up to six participants with a one week waiting period between each enrolled participant.Phase 1|Phase 2RecruitingDrug: INO-3107|Device: CELLECTRA™ 2000Learn more
Adjuvant PRGN-2012 in Adult Patients With Recurrent Respiratory Papillomatosis Recurrent respiratory papillomatosis (RRP) is a rare disease. It is caused by the human papillomavirus (HPV). RRP affects the upper and lower respiratory tracts. It is difficult to treat and can be fatal. Researchers want to see if PRGN-2012 can help.

The stated objective of this study is to find a safe, tolerable dose of PRGN-2012 and to see if it works in treating RRP.		Phase 1RecruitingDrug: PRGN-2012Learn more
M7824 in People With Recurrent Respiratory Papillomatosis Programmed cell death protein 1 (PD-L1) is a protein on the surface of cells. It regulates if a cell can be killed by immune system cells. It is thought to be able to affect the immune system response to diseased cells like those infected with a virus. The molecule M7824 interferes with the activity of PD-L1. It could help the immune system kill cells infected with a virus . Since recurrent respiratory papillomatosis is caused by a virus infection, this molecule could help.

The stated objective of this study is to see if M7824 works in treating recurrent respiratory papillomatosis.

Phase 2Active, not recruitingDrug: M7824Learn more
Avelumab for People With Recurrent Respiratory Papillomatosis Recurrent respiratory papillomatosis (RRP) is a rare disease caused by human papillomavirus. It can cause voice changes, airway compromise, pulmonary lesions, and cancers. Programmed death-ligand 1 (PD-L1) is a protein on cells. It may be able to stop or decrease the immune system s response to viruses such as human papillomavirus. The drug Avelumab interferes with the activity of PD-L1. Researchers want to see if Avelumab treats RRP and study its side effects.

The stated objective of this study is to see if Avelumab works in treating RRP and is safe.		Phase 2Active, not recruitingDrug: AvelumabLearn more
Pembrolizumab for HPV-associated Recurrent Respiratory Papilloma Patients With Laryngeal, Tracheal and/or Pulmonary Involvement This research study is evaluating an immune modulatory agent as a possible treatment for patients with Recurrent Respiratory Papillomatosis (RRP) with significant disease involving the larynx, trachea, and/or lungs. The investigators will be using Pembrolizumab as the treating agent.Phase 2Active, not recruitingDrug: PembrolizumabLearn more
Lenvatinib and Pembrolizumab Combination Therapy In HPV-associated Recurrent Respiratory Papilloma Patients With Laryngeal, Tracheal, and/or Pulmonary InvolvementThis research study is studying Lenvatinib in combination with Pembrolizumab in people with human papillomavirus (HPV)-associated recurrent respiratory papillomatosis (RRP).Phase 2Not yet recruitingDrug: Lenvatinib|Drug: PembrolizumabLearn more

Top treatments in development

AgentClass/Mechanism of ActionDevelopment StatusCompanyClinical StudiesMore Information
PRGN-2012PRGN-2012 is an innovative therapeutic vaccine with optimized antigen design that uses Precigen’s gorilla adenovector technology, part of Precigen’s proprietary AdenoVerse platform, to elicit immune responses directed against cells infected with human papillomavirus (HPV) type 6 (HPV 6) or HPV type 11 (HPV 11)Phase 1Precigen, Inc. - PRGN-2012 is being developed through a Cooperative Research and Development Agreement (CRADA) with NCI’s Center for Cancer Research (CCR) and Precigen Inc. https://clinicaltrials.gov/ct2/results?cond=&term=PRGN-2012&cntry=&state=&city=&dist=Learn more
PembrolizumabPembrolizumab binds to the PD⁠-⁠1 receptor, blocking both immune-suppressing ligands, PD‑L1 and PD‑L2, from interacting with PD⁠-⁠1 to help restore T-cell response and immune response.Phase 2Pembrolizumab is being evaluated by Massachusetts General Hospital.
Pembrolizumab was developed by Merck Sharp & Dohme Corp., and is sold under the brand name Keytruda.		https://clinicaltrials.gov/ct2/results?cond=RRP&term=Pembrolizumab&cntry=&state=&city=&dist=Learn more
M7824As a fusion protein (made from a fusion gene created by joining parts of two different genes), M7824 is designed to block two signaling pathways commonly used by cancer cells to avoid being destroyed by the immune system. M7824 consists of a monoclonal antibody against a protein called programmed death-ligand 1 (PD-L1) linked to the extracellular domain of the human transforming growth factor beta (TGF-β) receptor 2 protein.

Phase 2M7824 is being evaluated in RRP by the National Cancer Institute (NCI)https://clinicaltrials.gov/ct2/results?cond=&term=M7824&cntry=&state=&city=&dist=Learn more
LenvatinibLenvatinib acts as a multiple kinase inhibitor. It inhibits the three main vascular endothelial growth factor receptors VEGFR1, 2 and 3, as well as fibroblast growth factor receptors (FGFR) 1, 2, 3 and 4, platelet-derived growth factor receptor (PDGFR) alpha, c-Kit, and the RET proto-oncogene.Phase 2Lenvatinib (in combination with Pembrolizumab) is being evaluated by Massachusetts General Hospital. Lenvatinib was developed by Eisai, Inc., and is sold under the brand name Lenvima.https://clinicaltrials.gov/ct2/results?cond=RRP&term=Lenvatinib&cntry=&state=&city=&dist=Learn more
INO-3107/ CELLECTRA™ 2000INOVIO's DNA medicines deliver optimized plasmids directly into cells intramuscularly or intradermally using INOVIO's proprietary hand-held smart device called CELLECTRA®. The CELLECTRA device uses a brief electrical pulse to reversibly open small pores in the cell to allow the plasmids to enter, overcoming a key limitation of other DNA and other nucleic acid approaches, such as mRNA. Once inside the cell, the DNA plasmids enable the cell to produce the targeted antigen. The antigen is processed naturally in the cell and triggers the desired T cell and antibody-mediated immune responses. Administration with the CELLECTRA device ensures that the DNA medicine is efficiently delivered directly into the body's cells, where it can go to work to drive an immune response. INOVIO's DNA medicines do not interfere with or change in any way an individual's own DNA. The advantages of INOVIO's DNA medicine platform are how fast DNA medicines can be designed and manufactured; the stability of the products, which do not require freezing in storage and transport; and the robust immune response, safety profile, and tolerability that have been demonstrated in clinical trials.Phase 1/2Inovio Pharmaceuticalshttps://clinicaltrials.gov/ct2/results?cond=&term=INO-3107&cntry=&state=&city=&dist=Learn more