Disease Analysis: Osteoporosis

Disease Overview

Osteoporosis is the most common metabolic bone disease, and is characterized by compromised bone strength which predisposes individuals to an increased risk of fracture. Bone strength itself is not directly measurable, but can be inferred from bone mass and quality, with bone mass being most commonly approximated by assessing bone mineral density (BMD). A person with a BMD measurement that falls within one standard deviation (SD) of the healthy reference (30-year-old male or female) is considered to have healthy bone mass and structure (T-score >-1).

Latest key takeaways

• Datamonitor Healthcare estimates that in 2018, there were 345.8 million prevalent cases of osteoporosis among adults aged 50 years and older worldwide, and forecasts that number to increase to 427.8 million prevalent cases by 2027.
• With first-line bisphosphonates largely genericized, Prolia has been an important growth driver in the osteoporosis market, with flexible positioning as an alternative initial therapy for postmenopausal women with osteoporosis who are at high risk for osteoporotic fractures or do not tolerate bisphosphonates, or as an indefinite follow-on option after completion of anabolic therapy. Growth appeared to plateau in 2020, but that may have been due to the COVID-19 pandemic, as it appears to be picking up again in 2021. However, patent expirations in the US and other major markets in 2025 will open the door to biosimilars.
• In the anabolic segment, the value of the class has been impacted by Forteo’s loss of exclusivity in 2019 and the arrival of two cheaper anabolic therapies, Tymlos in the US and Evenity. Dynamics have been somewhat different according to geography. In the US, despite an initial decline in 2018, with the subsequent growth of Tymlos and Evenity, as well as limited penetration of the biosimilar Bonsity, sales of the segment have been modestly increasing. Outside the US, where there has been more biosimilar competition and Tymlos is awaiting approval/launch in major markets, sales of the branded segment started to decrease after 2019.
• Tymlos and Evenity are expected to take significant market share from Forteo due to their competitive efficacy profiles. Evenity additionally has convenient monthly dosing over 12 months and, in the US, certain advantages of reimbursement as a physician-administered drug, with co-marketing with Prolia. A black box warning for increased CV risk is somewhat of a barrier, despite some ways of mitigating the risk, though it is starting to surpass Tymlos in US sales.
• In addition to safety concerns and restrictions on the duration of dosing, use of anabolic therapies remains limited due to their nature as injectable therapies (daily in the case of Forteo and Tymlos), which is associated with poor compliance and adherence. While Radius Health was hoping to overcome this with a transdermal formulation of Tymlos, it failed to show non-inferiority with the injected formulation, and it is unclear if the company will move forward with an enhanced version.
• The overall likelihood of approval of a Phase I osteoporosis asset is 4.7%, and the average probability a drug advances from Phase III is 72.2%. Osteoporosis drugs, on average, take 10.4 years from Phase I to approval, versus 9.8 years in the overall endocrine space.