Comparison of Forteo and Teriparatide on Improvements in Bone Mineral Density

PF708 teriparatide, manufactured by Alvogen, was approved through the 505(B)(2) application after the expiration of Forteo market exclusivity in October 2019. The 505(B)(2) application allows safety and efficacy information to come from studies not conducted by the applicant if it is demonstrated that the proposed product shares characteristics (active ingredient, dose, route of administration, strength) with the reference product and comparable pharmacokinetic data is established. Real-world data is thus needed to demonstrate equivalent safety and efficacy between Forteo and PF708 teriparatide. The purpose of this study was to evaluate changes in bone mineral density in osteoporotic patients treated with either Forteo or PF708 teriparatide for 18-24 months. This retrospective chart review included osteoporotic patients>18 years of age who received PF708 teriparatide or Forteo prescriptions from the practice location and initiated therapy between October 1, 2019 and October 31, 2022. The primary endpoint was percent change from baseline in BMD of the lumbar spine, femoral neck, and total hip. A total of 108 patients were included: 27 (median age 67 years, 88.9% female) in the PF708 teriparatide group and 81 (median age 68 years, 85.2% female) in the Forteo group. There was no significant difference in median change from baseline BMD of lumbar spine (+9.6% vs +7.7%, P= 0.56), left femoral neck (1.5% vs 2.8%, P= 0.39), right femoral neck (+1.6% vs +4.4%, P= 0.14), left total hip (+2.4% vs +3.2%, P= 0.24), or right total hip (0.0% vs +1.4% , P= 0.71) with PF708 teriparatide vs Forteo, respectively. In this small retrospective study, effect on BMD and reported adverse events were similar between PF708 teriparatide and Forteo when used for the recommended duration of therapy.

💡 Research Summary

The study set out to determine whether PF708 teriparatide, a generic version of the anabolic osteoporosis drug marketed by Alvogen and approved via the FDA’s 505(b)(2) pathway, delivers comparable clinical outcomes to the reference product, Forteo (teriparatide). The 505(b)(2) route permits reliance on existing safety and efficacy data from the reference product, provided the applicant can demonstrate that the new product shares the same active ingredient, dose, route, strength, and pharmacokinetic profile. While this regulatory shortcut accelerates market entry, it leaves a gap in real‑world evidence of therapeutic equivalence, especially regarding bone mineral density (BMD) gains and adverse event profiles.

To fill this gap, the investigators performed a retrospective chart review of osteoporotic patients aged 18 years or older who initiated either PF708 or Forteo between 1 October 2019 and 31 October 2022 at a single practice. A total of 108 patients met inclusion criteria: 27 received PF708 (median age 67 years, 88.9 % female) and 81 received Forteo (median age 68 years, 85.2 % female). The primary endpoint was the percent change from baseline in BMD at the lumbar spine, left and right femoral necks, and left and right total hips after 18–24 months of therapy.

The results showed no statistically significant differences between the two groups. Lumbar spine BMD increased by 9.6 % with PF708 versus 7.7 % with Forteo (P = 0.56). Left femoral neck BMD rose 1.5 % versus 2.8 % (P = 0.39), right femoral neck 1.6 % versus 4.4 % (P = 0.14), left total hip 2.4 % versus 3.2 % (P = 0.24), and right total hip 0.0 % versus 1.4 % (P = 0.71). Reported adverse events were described as similar between groups, although the manuscript does not provide detailed incidence data.

Interpretation of these findings must consider several methodological constraints. First, the retrospective, non‑randomized design introduces potential selection bias; clinicians may have preferentially prescribed one product over the other based on unrecorded patient characteristics. Second, the sample size, especially for the PF708 cohort, is modest, limiting statistical power to detect small but clinically meaningful differences. Third, confounding variables such as baseline fracture risk, concomitant osteoporosis therapies, comorbidities, and lifestyle factors were not controlled for, which could influence BMD response. Fourth, BMD change, while an accepted surrogate marker, does not directly equate to fracture risk reduction; the study does not report fracture outcomes, mortality, or quality‑of‑life measures. Finally, adverse event reporting relied on chart documentation, which may under‑capture mild or transient side effects.

Despite these limitations, the study provides early real‑world evidence that PF708 teriparatide achieves BMD improvements comparable to those of Forteo over the recommended treatment duration. This suggests that the generic product can be considered therapeutically equivalent in terms of efficacy and short‑term safety, supporting its use as a cost‑effective alternative. The findings have practical implications: clinicians may feel more confident prescribing PF708, patients may benefit from lower out‑of‑pocket costs, and payers may achieve savings without compromising care quality.

Future research should aim for prospective, randomized, adequately powered trials that include hard clinical endpoints such as incident vertebral and non‑vertebral fractures, hospitalization rates, and patient‑reported outcomes. Long‑term safety surveillance, including rare adverse events, is also essential. Moreover, post‑marketing pharmacovigilance programs could systematically collect real‑world data to validate the equivalence demonstrated in this study. From a regulatory perspective, the FDA and other agencies may consider requiring such post‑approval evidence for 505(b)(2) products, ensuring that the expedited pathway does not compromise the ultimate goal of patient safety and therapeutic effectiveness.