Osteoporosis treatment options - down to the bare bones

It is World Osteoporosis Day this month, and Ben Hargreaves takes a look at what treatment options look like for patients living with the disease.

Osteoporosis is a condition that causes bones to become weak and fragile, making them more likely to break due to a fall or even something as minor as a sudden movement. The condition is the most common chronic bone disease, which is more often seen in the elderly population. In many nations across the world, the population aged 65 and older is growing faster than the total population, which means diseases related to age are becoming increasingly prevalent and will require effective treatments.

However, there is a problem facing the treatment of osteoporosis, and it is the lack of research into new therapies, leading to a limited pipeline of new treatments coming through. In the UK, a new treatment was recently approved for severe osteoporosis in the form of Evenity (romosozumab), but only after a wait of more than a decade. Standard treatments for osteoporosis are usually bisphosphonates, such as alendronate or risedronate, with these types of treatments approved for use decades ago. This raises the question of why investment has been slow in the area, and are there signs of change on the horizon?

A sparse pipeline

In 2021, Michael McClung, a founding director of the Oregon Osteoporosis Center, outlined that the pipeline for potential new treatments for osteoporosis was bare and stated that it would be a number of years before new treatments would emerge for the condition. ResearchandMarkets also recently published a report, which highlighted only biosimilars as the emerging treatments for osteoporosis.

In September 2022, the International Osteoporosis Foundation (IOF), alongside the NCD Alliance, called for greater action and investment to be targeted at non-communicable diseases (NCDs). The organisations outlined that although the diseases are mostly preventable, they remain the number one cause of death and disability worldwide.

IOF CEO, Philippe Halbout, stated: “Within the spectrum of NCDs, osteoporosis and related musculoskeletal diseases are too often disregarded. Many people don’t realize that fractures due to osteoporosis are often life-changing events that bring pain, immobility, isolation, and dependency. For older adults affected by a fragility fracture, even simple, everyday tasks can become difficult or even impossible, placing a significant toll on the patients and their informal carers.”

Halbout continued to say that due to an ageing global population, the projected healthcare costs due to fragility fractures are set to rise enormously in the years to come. It is projected that this could lead to a situation where the economic burden would be “unsustainable for most healthcare systems,” he concluded.

A biologic breakthrough

One of the few new treatments to emerge in the space was the previously mentioned approval for Evenity, a monoclonal antibody treatment. The therapy has been on the market in Europe since 2019, which is marketed by UCB in the region, though by Amgen and Astellas in other areas. UCB recently revealed that a study had been carried out using 3D modelling to visualise and assess on-going treatment for osteoporosis. The study found that those patients treated with Evenity achieved increases in cortical volumetric bone mineral density (BMD), cortical thickness, cortical surface BMD, and trabecular volumetric BMD, when compared against comparator groups.

Cesar Libanati, head of bone medical strategy at UCB, spoke with pharmaphorum about the results of the study and about osteoporosis treatment in general. Regarding the condition in Europe, Libanati outlined, “osteoporosis and the 4.3 million fragility fractures it causes each year cost the health care systems in excess of €56 billion, based on data for 2019. Only 3% of this money was spent on medical treatment.”

Regarding how Evenity is able to offer advantages over standard treatment, Libanati stated that it is the only therapy available that has a dual effect – of increasing bone formation and decreasing bone resorption. He added further, “Our data show that romosozumab’s dual effect leads to greater improvements in BMD in the spine and hips when compared to other available treatments. Greater improvements in BMD result in larger gains in bone strength and are associated with significant reductions in future fracture risk.”

The ability to use 3D modelling now presents researchers with greater detail into how treatments are working, as there is no risk of the radiation associated with a computerised tomography (CT) scan. At a patient-level, this allows researchers to understand the impact of therapies in the different compartments of bone and therefore to better tailor individualised patient treatment options.

Emerging research and biosimilars

Amgen reported full year, global sales for Evenity as reaching $530 million in 2021. The company also has another product in its portfolio for osteoporosis, in the form of denosumab, which has become crucial to its overall revenue and a blockbuster treatment. The level of revenue for these osteoporosis treatments should suggest the attraction of working in the area and this has become true, but mainly for those companies working on biosimilars.

Sandoz recently announced positive clinical trial results from a phase 1/3 into its biosimilar to denosumab. Sandoz is only one of a number of companies looking to progress their own biosimilars, a list which includes Samsung Bioepis, Celltrion, and AryoGen Pharmed. As the patents for denosumab expired in some European markets in June 2022, should these treatments be deemed equivalent by the European Commission then they could emerge on the market shortly. However, patent protection remains in some major markets, including France, Italy, Spain, and the UK until 2025.

However, though biosimilars will offer cheaper treatment options to healthcare systems, they do not offer advances on current treatments or provide patients with an alternative type of treatment. As a result, there will still be pressure to develop new therapies going forward. Amgen’s portfolio has proven that this kind of treatment can be lucrative. The question is whether other major pharmaceutical companies will be attracted to the space – particularly when areas such as oncology and orphan drugs currently provide a larger return on investment.