Sandoz' Omnitrope Supported by Long-Range Swedish Study

Swedish investigators who studied biosimilar biosimilar recombinant human growth hormone (rhGH; Omnitrope) for more than 10 years in patients with growth hormone deficiencies (GHD) concluded that the Sandoz drug is safe and effective and comparable to other rhGH treatments for adults and children.

This is the first report of long-term findings, and these were based on the PATRO studies on the effects of biosimilar rhGH in Swedish children and adults. The data spanned 2007 to 2019. Investigators enrolled 136 children and 293 adults.

Biosimilar rhGH was approved by the European Medicines Agency in 2006. The drug was also approved for marketing by FDA in 2006, but it is not considered a biosimilar in the United States because it was approved prior to establishment of the biosimilar pathway.

Safety Analysis

Investigators said there were no severe adverse events (AEs) in children for diabetes, impaired glucose tolerance, or malignancy; they also said there were no clinically relevant anti—human growth hormones or neutralizing antibodies observed.

Overall, 35% of participants (n = 47) reported 121 AEs, with just 1% of AEs suspected to be related to treatment with the biosimilar. Overall, 20 events in 11 patients (8%) were considered serious but not treatment related. The most common AE was nasopharyngitis (12%), followed by ear infection, varicella, and viral infection (4% each).

Drug-related AEs occurred in 26 patients (9%), with severe drug-related AEs reported in 6 patients. In adults, the most common drug-related AEs were fatigue (8.9%), arthralgia (5.8%), headache (4.4%), and nasopharyngitis (4.4%). In children, the most common AEs were nasopharyngitis (11.8%), ear infection (3.7%), varicella (3.7%), and viral infection (3.7%).

Changing treatment from reference rhGH to biosimilar rhGH in children was not associated with any safety issues. No diabetes, impaired glucose tolerance, or malignancies were reported in child participants, which is consistent with previous studies.

Onset of type 2 diabetes after starting rhGH treatment was reported in 4 adult patients. “None of the cases of diabetes mellitus onset were considered related to rhGH treatment,” although for 1 patient worsening of diabetes occurred simultaneously with treatment initiation, and so treatment with biosimilar rhGH was stopped for that patient.

“Regarding the onset of diabetes mellitus, rhGH treatment might impair glucose metabolism, especially in obese patients with a family history of diabetes mellitus,” the investigators wrote.

In all, 47 patients (16%) discontinued treatment, and of these, 17 patients discontinued treatment because of an AE.

Switching to Biosimilar rhGH

Investigators said the main reason a pediatric patient will change to biosimilar rhGH is economic. They said patients may require time-consuming re-education, which may affect convenience of therapy, efficacy, and adherence. However, they noted, changes may improve compliance if the switch is more acceptable for patients.

“In our study, we did not see any negative effects associated with changing to biosimilar rhGH, and reported AEs were mild, supporting earlier analyses that found switching to biosimilar rhGH had no impact on safety,” the investigators wrote.

In Sweden, the recommended rhGH dose in patients with GHD is 0.033 mg/kg/day, and in randomized clinical trials, an rhGH dose of 0.067 mg/kg/day during puberty has shown higher growth response compared with standard doses.

Some clinicians used lower doses in the PATRO study, which investigators attributed partly to studies linking rhGH to a higher risk of mortality due to bone tumors and cerebrovascular disease. “Concerns about the consequences of rhGH dosage remain, and the consensus is to use the lowest effective dose if therapy is started,” the investigators wrote.

“Use of rhGH doses below those recommended may be explained by caution among physicians in the use of a clinically new drug,” the investigators added.

They said further long-term studies in larger populations are needed to confirm the results. However, “based on over 10 years of observation in real-life clinical practice, the available data suggest that biosimilar rhGH is well tolerated and effective across pediatric and adult indications.”

Sandoz has 8 biosimilar products on the market. Its most recent launch, Ziextenxo, is a long-acting pegfilgrastim product. Sheila Frame, US head of Marketing and Market Access and Patient Services for Sandoz, discussed the company's vision for biosimilar development in a recent interview with The Center for Biosimilars^®.

Reference

Lundberg E, Kriström B, Zouater H, Deleskog A, Höybye C. Ten years with biosimilar rhGH in clinical practice in Sweden—experience from the prospective PATRO children and adult studies. BMC Endocr Disord. 2020;20(1):55. doi:10.1186/s12902-020-0535-4.