Section 3 of 6
Product information and disease description
78 evidence topics · 58 sources
Product description
Phase of product development
FDA submission: regulatory pathway
Anticipated approval and commercial launch
Launch: Anticipated in the first half of 2027
Special FDA designations: Breakthrough Therapy designation
Special FDA designations: Fast Track designation
Special FDA designations: FDA orphan-drug database
| Information | Source quotation |
|---|---|
| Date designated | “08/03/2021” |
| Orphan designation | “Treatment of Lymphatic Malformations” |
| FDA orphan approval status | “Not FDA Approved for Orphan Indication” |
Special designations: European Medicines Agency
Product information
Generic, brand name and therapeutic class of product
Manufacturer: Palvella Therapeutics
| Field | Quoted record |
|---|---|
| Sponsor | “Palvella Therapeutics, Inc.” |
Dosage forms and strengths
Topical formulation and strength
Material safety data sheet
No evidence found.
Average sales price and wholesale acquisition cost
Summary
The sponsor describes a potential annual pricing range of approximately $100,000 to $200,000 per patient. The cited presentation does not identify this range as an established ASP or WAC.
Established average sales price and wholesale acquisition cost
No evidence found.
American hospital formulary service (AHFS), or other drug classification
Product-specific AHFS classification
No evidence found.
Indication
Pharmacology
Mechanism of action
Local inhibition of mTOR signaling: formulation design
Pharmacodynamics
Pharmacokinetics
SELVA: rapamycin pharmacokinetics
Contraindications/Warnings/Precautions/Adverse effects
Warnings and precautions
Not applicable.
Special populations
SELVA: pregnancy-related exclusion criterion
Renal impairment
No evidence found.
Hepatic impairment
No evidence found.
Lactation
No evidence found.
Drug/Drug, drug/disease interactions
Effects of other drugs on sirolimus
No evidence found.
Effects of sirolimus on other drugs
No evidence found.
Dosing and administration
Dosage
Dosing and administration: phase 3
Administration
Dosing and administration: phase 2
Access and distribution
Co-prescribed/Concomitant therapies
No evidence found.
Effect of sirolimus on quality measures
No evidence found.
Product comparison
No evidence found.
Place of product in therapy
Disease description
Definition and etiology
Developmental lymphatic-vessel defects
Epidemiology
Incidence of Microcystic lymphatic malformations
Incidence: lymphatic malformations overall
Microcystic-specific incidence
No evidence found.
Prevalence of Microcystic lymphatic malformations
Epidemiology: microcystic lymphatic malformations
Epidemiology: lymphatic malformations with a cutaneous component
Annual managed prevalence: distinction from total national prevalence
Natural history, survival, and mortality
Spontaneous regression: head and neck lymphatic malformations
Lymphatic malformations: complications affecting vital functions
Microcystic-specific survival and mortality estimates
No evidence found.
Pathophysiology
Genetics, mechanisms, and therapeutic strategies
Diagnosis
Clinical presentation - signs and symptoms
Cutaneous symptoms: lymphorrhea, bleeding, pain, itching, and malodor
Infectious and inflammatory symptoms: pain and chronic oozing wounds
Long-term morbidity
Skeletal and dental complications: tongue involvement
Burden of Microcystic lymphatic malformations
Humanistic burden and health-related quality of life
Long-term health-related quality of life: comparison with population norms
Patient-reported outcomes: Lymphatic Malformation Function instrument
Patient-reported outcomes: functional and symptom impacts in pediatric head and neck lymphatic malformations
Economic burden and healthcare resource utilization
Pediatric lymphatic malformations: United States inpatient burden, study years
Pediatric lymphatic malformations: United States inpatient burden, hospital charges
Economic impact of Microcystic lymphatic malformations on families
Caregiver employment: interruption of professional activity
Quantified family out-of-pocket costs and productivity losses
No evidence found.
Economic impact of diagnostic testing
No evidence found.
Approaches to treatment
Current treatment options and standard of care
Conservative and supportive care
Multidisciplinary treatment decisions
Sclerotherapy
Guideline-listed treatment for skin and mucosal lymphatic malformations
Surgical resection
Guideline-listed treatment for skin and mucosal lymphatic malformations
Electrocoagulation
Guideline-listed treatment for skin and mucosal lymphatic malformations
Laser therapy
Guideline-listed treatment for skin and mucosal lymphatic malformations
Radiofrequency ablation
Guideline-listed treatment for skin and mucosal lymphatic malformations
Topical mTOR inhibitors
French national diagnosis and care protocol: topical sirolimus
Medical therapies for pediatric lymphatic malformations: systematic review
Other topical sirolimus formulations: 0.2% gel in pediatric superficial microcystic lymphatic malformations, case series
Other topical sirolimus formulations: upper limb superficial lymphatic malformation case report
Other topical sirolimus formulations: 1% rapamycin ointment case report
Other topical sirolimus formulations: microcystic lymphatic malformation case report with local irritation
Other topical sirolimus formulations: efficacy and absorption in children with vascular anomalies
Compression therapy and lymphatic drainage
Systemic mTOR inhibitors
Sirolimus for pediatric head and neck lymphatic malformations: systematic review
PI3K inhibitors
Kampo herbal formulas
Japanese guideline: geographically limited use
Limitations of current therapies
Summary
Available procedural treatments can be limited by complications, recurrence, and repeated procedures. The Japanese guideline recommendation addressing skin and mucosal lymphatic malformations has a strength rating of 2, described as weak, and an evidence rating of D, described as very weak.
A systematic review of sirolimus reported improvement in 46 of 50 evaluable individuals (92%), mostly previously treated, while identifying the need for prospective controlled trials. These heterogeneous supporting data do not establish the comparative effectiveness of QTORIN rapamycin against individual procedures, compounded topical formulations, or systemic therapy.
Japanese clinical practice guidelines: CQ37 strength of recommendation
Japanese clinical practice guidelines: CQ37 evidence
Japanese clinical practice guidelines: complications and recurrence
Place in treatment, anticipated use, and care setting
Summary
QTORIN rapamycin has been studied as a self-administered topical treatment. SELVA required clinically confirmed superficial/cutaneous microcystic lymphatic malformations and excluded complicated vascular anomalies with severe systemic symptoms requiring systemic therapy. The sponsor describes the diagnosed population as concentrated in vascular anomaly centers. The report does not establish an approved treatment sequence or an approved prescribing setting for this investigational formulation.
Heterogeneity of treatment effect
SELVA: pediatric subgroup
| Information | Source quotation |
|---|---|
| Subgroup | “aged 6–11 years (n=13)” |
| Mean response | “(mLM-IGA) of +2.46 at Week 24 (p<0.001).” |
| Response proportion | “100% of participants in this cohort” |
SELVA: pediatric subgroup response categories
Formal treatment-by-subgroup interaction analyses
No evidence found.
Care management intervention strategies
Patient and caregiver education: disease-awareness campaign
Other product development or post-marketing obligations required by the FDA
Not applicable.
Ongoing post-approval monitoring
Not applicable.