SOHONOS

What it is

SOHONOS is a hard capsule formulation containing palovarotene, available in strengths of 1 mg, 1.5 mg, 2.5 mg, 5 mg or 10 mg. Palovarotene is a retinoic acid receptor gamma (RARγ) selective agonist. The medicinal product is subject to additional monitoring in Australia, which will allow quick identification of new safety information.

Approved indications

— Reducing the formation of heterotopic ossification in adults and children aged 8 years and above for females and 10 years and above for males with fibrodysplasia ossificans progressiva (FOP).

Dosing overview

SOHONOS should only be prescribed under the supervision of specialist medical practitioners with expertise in managing fibrodysplasia ossificans progressiva (FOP). The recommended dosing includes a chronic treatment dose which can then be adjusted in the event of flare-up symptoms. For adults and children aged 14 years and over, the recommended chronic treatment dose is 5 mg once daily. The recommended flare-up treatment dose is 20 mg once daily for 4 weeks, followed by 10 mg once daily for 8 weeks for a total of 12 weeks. Weight-adjusted dosing is required in children who are under 14 years of age. SOHONOS should be taken with food preferably at the same time each day.

Key safety warnings

SOHONOS must not be used by female patients who are, or intend to become, pregnant, as it is to be administered only if conditions for pregnancy prevention are met due to the risk of teratogenicity and to minimise fetal exposure. Studies in pregnant rats have shown that administration of palovarotene resulted in fetal malformations typical of retinoids, including cleft palate, misshapen skull bones, and shortening of the long bones. SOHONOS may cause premature physeal closure in growing patients and close monitoring is recommended. Premature physeal closure (PPC) has been demonstrated to be an important risk associated with palovarotene treatment in growing children with FOP, identified as an irreversible serious risk. Twenty-seven (26.5%) palovarotene treated paediatric subjects less than 18 years of age reported PPC, with 13 of 42 subjects from 8 or 10 to less than 14 years (31%) and 14 of 25 subjects less than 8 or 10 years (56%). Prior to starting treatment, all growing children should undergo baseline clinical and radiological assessments including an assessment of skeletal maturity via hand/wrist and knee x-rays, standard growth curves and pubertal staging, with continued monitoring recommended every 6 to 12 months until patients reach skeletal maturity or final adult height. Retinoids are associated with bone toxicity, and in clinical trials palovarotene has resulted in decreased vertebral bone mineral content, bone density and bone strength as well as an increased risk of radiologically observed vertebral fractures in treated adult and paediatric patients compared to untreated patients. Periodic radiological assessment of the spine is recommended. Mucocutaneous effects are the most commonly reported adverse reactions during clinical studies with SOHONOS (98%) and were generally mild to moderate in severity, with reactions observed in over 10% of subjects including dry skin (80%), pruritus (56%), alopecia (42%), rash (41%), erythema (35%), skin exfoliation (32%), drug eruption (20%), eczema (15.8%) and skin irritation (12%). SOHONOS may contribute to an increased risk of skin and soft tissue infections, particularly paronychia and decubitus ulcer, due to a decreased skin barrier from mucocutaneous effects such as dry and peeling skin. Prophylactic measures to minimize risk and/or treat the mucocutaneous effects are recommended, such as skin emollients, sunscreen, or other helpful treatments. Photosensitivity reactions, such as exaggerated sunburn reactions involving areas exposed to the sun, have been associated with the use of retinoids. Excessive exposure to sun or artificial ultraviolet light should be avoided, and protection from sunlight should be used when exposure cannot be avoided through use of sunscreens, protective clothing, and use of sunglasses. Depression, depression aggravated, anxiety, mood alterations, and suicidal thoughts and behaviours have been reported in patients treated with systemic retinoids and individuals with a personal history of psychiatric illness appear to be more susceptible. Particular care should be taken in patients with history of psychiatric illness, and patients should be monitored for signs of depression and referred for appropriate treatment if necessary. Night blindness (nyctalopia) has been reported in patients exposed to systemic retinoids and palovarotene, with a single instance observed in the SOHONOS development program.

Contraindications

SOHONOS is contraindicated in patients with a history of allergy or hypersensitivity to the active substance, or to other retinoids or to any of the excipients. SOHONOS is contraindicated in women who are pregnant or breastfeeding. SOHONOS is contraindicated in females of childbearing potential unless all of the conditions of the pregnancy prevention are met, or they are not at risk for pregnancy.

PBS listing

SOHONOS is listed on the PBS in five strengths: 1 mg (A$9990.40 ex-manufacturer price), 1.5 mg (A$14985.60), 2.5 mg (A$24976.00), 5 mg (A$49952.00), and 10 mg (A$99904.00). Restrictions include authority required and streamlined mechanisms depending on the strength.

Regulatory history

SOHONOS was approved by the TGA on 27 November 2023 for the indication to reduce the formation of heterotopic ossification in adults and children aged 8 years and above for females and 10 years and above for males with fibrodysplasia ossificans progressiva (FOP). The product was first listed on the ARTG on 28 November 2023 in five strength formulations (1 mg, 1.5 mg, 2.5 mg, 5 mg, and 10 mg capsules). In November 2024, the PBAC recommended SOHONOS for listing on the General Schedule with Authority Required (Written) restriction, noting high clinical need, reduction in heterotopic ossification, and cost-effectiveness with a price reduction and risk-sharing arrangement.