Alfacalcidol approvals increase with expansion of Prolia biosimilars

Seven alfacalcidol products approved this year... Prolia biosimilars enter three-way race

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As biosimilars for the osteoporosis treatment ‘Prolia (denosumab)’ continue to emerge, products containing the active ingredient alfacalcidol are also increasing.

Denosumab-based osteoporosis therapies have effectively dominated the market due to their strong bone mineral density–enhancing effects and patient convenience, as they are administered via subcutaneous injection once every six months.

However, because denosumab carries a risk of hypocalcemia, patients are required to take calcium and vitamin D supplements. As a result, the value of alfacalcidol, an “active form of vitamin D,” has also been increasing.

According to the Ministry of Food and Drug Safety (MFDS), seven alfacalcidol products have been approved so far in 2026. As of February 9, a total of 42 alfacalcidol products have been approved, with 27 products (over 60%) receiving approval since 2025.

Yuyu Pharma has emerged as a major contract manufacturer for alfacalcidol products. Meanwhile, YS Life Science, which has developed tablet formulations that are easier to swallow than capsules, is also expanding its contract manufacturing business. Notably, all three recently approved products are tablet formulations manufactured by YS Life Science.

The recent increase in alfacalcidol product development is closely linked to the expansion of the denosumab biosimilar market. The compound patent for Prolia, which accounts for approximately KRW 1.7 trillion in annual market size in Korea, expired in March 2025.

Following the patent expiration, Celltrion and Samsung Bioepis launched biosimilar products last year, and on February 4, HK inno.N received approval for its denosumab biosimilar, Izambia Prefilled Syringe. With the entry of additional biosimilars, the overall market size is expected to continue growing further.

Denosumab inhibits osteoclast activity, thereby preventing bone destruction and increasing bone mineral density. It offers improved convenience in administration with a single subcutaneous injection every six months.

However, because it strongly suppresses bone resorption, there is concern that it may increase the risk of hypocalcemia, particularly in patients with chronic kidney disease or those undergoing dialysis.

In 2024, the U.S. Food and Drug Administration (FDA) added a boxed warning to the Prolia label regarding the increased risk of severe hypocalcemia in patients with advanced chronic kidney disease. This update, based on clinical data, has also been reflected in Korea’s label and indication as well.

Accordingly, healthcare providers are advised to monitor patients for signs of hypocalcemia after Prolia administration and to prescribe calcium and vitamin D supplements concurrently.

Alfacalcidol is an active form of vitamin D that does not require renal activation, offering the advantage of reduced burden on the kidneys. For this reason, it has been gaining attention as a complementary therapy to Prolia. The indications for alfacalcidol are: ▲ Improvement of symptoms associated with vitamin D metabolism disorders in chronic renal failure, hypoparathyroidism, and vitamin D-resistant rickets/osteomalacia; ▲ Osteoporosis.

Looking ahead, alfacalcidol product development is expected to continue increasing through expanded contract manufacturing. An industry source commented, “As an over-the-counter drug, alfacalcidol faces no bioequivalence regulations, making contract manufacturing easy and straightforward. Coupled with the anticipated market expansion due to the emergence of denosumab biosimilars, it is expected to remain popular in the product development market for the foreseeable future.”