Abapatide in the field of osteoporosis treatment: an improved development path from subcutaneous injection to transdermal drug delivery-Industry News-Lindmik Pharmaceutical(Suzhou)Co.,Ltd

Today's topic
Abalopatide was approved by FDA for marketing in 2017 and PMDA of Japan in 2021. Its trade name is Tymlos. It is used for postmenopausal women with high risk of osteoporosis. The recommended daily dose is 80 mcg. Use a pre filled injection pen for subcutaneous injection. The volume of abalopatide contained in each injection pen can be injected 30 times.

（From the official website）

Appapatide was initially developed by Ipsen Pharmaceutical Company of France, and then authorized to be developed by Radius Health Biopharmaceutical Company of the United States, responsible for its listing and sales in the United States. Abapatide is a synthetic polypeptide with 34 amino acids. Its mechanism is the analog of parathyroid hormone related protein. It regulates metabolism and promotes bone formation by selectively activating the signal pathway of parathyroid hormone type 1 receptor.

Basic overview of osteoporosis
Osteoporosis OP is a systemic bone disease characterized by increased bone fragility and easy fracture caused by loss of bone mass, destruction of bone tissue microstructure or decrease of bone strength.

Osteoporosis can occur at any age, but it is more common in postmenopausal women and also in elderly men. Osteoporosis can be divided into two categories: primary and secondary. Primary osteoporosis includes postmenopausal osteoporosis (type I), senile osteoporosis (type II) and idiopathic osteoporosis. Secondary osteoporosis refers to osteoporosis caused by any disease affecting bone metabolism and (or) drugs and other clear causes.

OP Epidemiology

According to the data from the Health Commission (2018), the number of osteopenia and OP patients in China has reached more than 300 million, and the prevalence of OP among people over 50 years old is 19.2%. The prevalence of OP among people over 65 years old reached 32.0%, among which 51.6% were women.

Overview of OP treatment
The treatment plan of OP includes non drug treatment and drug treatment, and non drug treatment includes diet and exercise.

• Diet: Take adequate calcium and vitamins, and adopt a gluten free diet to improve bone density.

• Physical exercise

• Medication
Calcium absorption promoter: calcitriol, alfacalcinol
Bone resorption inhibitors: calcitonin; Diphosphates; Desumab, etc
Promoting bone formation: parathyroid hormone/parathyroid hormone related protein analogues: teripatide, abapatide

Abbapatide: subcutaneous injection changes the route of percutaneous penetration

Osteoporosis treatment requires long-term medication. The initial dosage form of abalone peptide is subcutaneous injection, but it is not easy to develop into oral dosage form as a polypeptide drug. Therefore, in order to improve drug compliance, Radius Health, the original research company, developed microneedle transdermal drug delivery. According to the registration requirements of 505b (2), the development path adopts the development strategy of large clinic, and the clinical scheme uses subcutaneous injection as the control. At present, it is in Ph3 stage.

Randomized single blind open label non inferiority bridge clinical trial design scheme
Phase	Enrollment	Interventional	Primary Endpoint	Results
3	474	Abaloparatide-SC	BMD （Time Frame:12 months）（percent change from baseline in BMD ）	Abalo-TD 7.1% (95% CI: 6.2, 8.0) vs. baseline Abalo-SC 10.9% (95% CI: 9.9, 11.8) vs. baseline Difference:-3.7% (95% CI: -5.0, -2.4)
		Abaloparatide-TD
2	250	Abaloparatide-SC	BMD （Time Frame:6 months）（percent change from baseline in BMD ）	NA
		Abaloparatide-TD
		Placebo
Note: BMD: bone mineral density Abaloparatide-SC：Abbapatide - subcutaneous injection; Abaloparatide TD: Abalapatide transdermal

According to the financial report of Radius Health, the sales of Tymlos in 2020 will be 208 million dollars and 219 million dollars in 2021. In the OP market, the sales volume is not bright, and it is far from the same mechanism drug terlipatide. Tripatide was originally developed as Lilly and was approved by FDA for listing in 2002. Its sales volume in 2019 has reached 1.4 billion US dollars. Tripatide is a First in class, which has a first mover advantage in the market. As a me-too, the market of abapatide is no longer friendly. Radius Health may be aware of this and take a differentiated competitive strategy to develop more compliant transdermal dosage forms. I wonder whether it can promote Tymlos to catch up or overtake at corners.

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