IBSA Pharma Inc. announced the voluntary recall of 27 lots of Tirosint^®-SOL (levothyroxine sodium) oral solution to the consumer level due to subpotency.

Tirosint-SOL is indicated as replacement therapy in primary (thyroidal), secondary (pituitary), and tertiary (hypothalamic) congenital or acquired hypothyroidism. It is also indicated as an adjunct to surgery and radioiodine therapy in the management of thyrotropin-dependent well differentiated thyroid cancer.

Testing of the oral solution revealed a slight decrease below 95% of the labeled amount in levothyroxine sodium (T4) for some lots. This recall does not apply to Tirosint (levothyroxine sodium) capsules.

Tirosint-SOL oral solution is supplied as 1mL unit dose ampules in 30-unit cartons. The 27 recalled lots were distributed to wholesalers, pharmacies, and health care providers. A complete list of recalled products can be found here.

To date, the Company has not received any reports of adverse events related to this recall. Adverse reactions or quality problems should be reported to the FDA’s MedWatch program.

Reference

IBSA Pharma Inc. issues voluntary nationwide recall of select lots of Tirosint^®-SOL (levothyroxine sodium) oral solution due to subpotency. News release. IBSA Pharma Inc. February 1, 2023. Accessed February 3, 2023. https://www.fda.gov/safety/recalls-market-withdrawals-safety-alerts/ibsa-pharma-inc-issues-voluntary-nationwide-recall-select-lots-tirosintr-sol-levothyroxine-sodium.

The Indications and Usage section of the Tepezza^® (teprotumumab-trbw) prescribing information has been updated to specify its use for the treatment of thyroid eye disease regardless of thyroid eye disease (TED) activity or duration.

In January 2020, the Food and Drug Administration (FDA) approved Tepezza, a human insulin-like growth factor-1 receptor inhibitor, for the treatment of TED in patients who had disease duration of 9 months or less and higher levels of disease activity.

The updated labeling was based on data from a randomized, double-masked, placebo-controlled phase 4 trial (ClinicalTrials.gov Identifier: NCT04583735) that evaluated the efficacy and safety of Tepezza in 62 adults who were diagnosed with TED 2 to 10 years prior to screening and had low levels of disease activity (clinical activity score of ≤1 in both eyes for at least 1 year prior to screening or all of the following 1 year prior to screening: no progression in proptosis, no progression in diplopia and no new inflammatory TED symptoms).

Results from the trial showed that treatment with Tepezza met the primary endpoint demonstrating statistically significant reductions in proptosis at week 24 compared with placebo. Moreover, a greater proportion of proptosis responders were reported in the Tepezza treatment arm compared with the placebo arm (key secondary endpoint). No new safety signals were observed.

“We worked closely with the FDA on this important label update, which further reinforces the potential benefit of Tepezza in people impacted by thyroid eye disease regardless of disease activity or duration,” said Tim Walbert, chairman, president and CEO, Horizon. “While Tepezza already had a broad indication for the treatment of thyroid eye disease, the new indication language now references treatment regardless of disease activity or duration.”

Tepezza is available as a 500mg lyophilized powder in a single-dose vial for intravenous infusion after reconstitution.

Tepezza^® (teprotumumab-trbw) significantly reduced proptosis in adults with chronic thyroid eye disease (TED) and chronic/low clinical activity score (CAS), according to data from a phase 4 trial.

The randomized, double-masked, placebo-controlled trial (ClinicalTrials.gov Identifier: NCT04583735) evaluated the efficacy and safety of Tepezza in 62 adults who were diagnosed with TED 2 to 10 years prior to screening and had low levels of disease activity (CAS of ≤1 in both eyes for at least 1 year prior to screening or all of the following 1 year prior to screening: no progression in proptosis, no progression in diplopia and no new inflammatory TED symptoms). The original approval of Tepezza was based on study data that included patients with disease duration of 9 months or less and higher levels of disease activity.

Among the study participants in the phase 4 trial, the mean duration of TED was 5.2 years and mean CAS was 0.4. Patients were randomly assigned 2:1 to receive either Tepezza 10mg/kg for the first intravenous (IV) infusion followed by 20mg/kg every 3 weeks for 7 additional infusions or placebo. The primary endpoint was the change from baseline to week 24 in proptosis in the study eye.

Results showed that treatment with Tepezza met the primary endpoint demonstrating the following reductions in proptosis at week 24 compared with placebo, respectively:

• Reduction in proptosis (intent-to-treat): 2.41mm vs 0.92mm (P =.0004)
• Reduction in proptosis (per protocol): 2.44mm vs 0.69mm (P =.0006)

At week 24, the proportion of proptosis responders (defined as the percentage of patients with 2mm or greater reduction in proptosis in the study eye from baseline; key secondary endpoint) was 62% vs 25% (P =.0134) in the intent-to-treat population and 63% vs 7% (P =.0008) in the per protocol population. No new safety signals were observed during the trial.

“We are thrilled with the topline results, which reinforce that Tepezza significantly reduces proptosis in people living with thyroid eye disease, regardless of their disease activity or duration, and underscores what we learned from our initial trials and what we have seen through more than 3 years of real-world use of Tepezza,” said Elizabeth H.Z. Thompson, PhD, executive vice president, research and development, Horizon. “With Tepezza, physicians have a medicine that can be used in a broad range of thyroid eye disease patients, including those with long-duration disease of more than 5 years on average in this trial, which is important because we know the negative impact of the disease can be significant across all types of thyroid eye disease patients. We look forward to discussing these data with the FDA to determine our next steps.”

Tirosint-SOL is indicated as a replacement therapy in primary (thyroid), secondary (pituitary), and tertiary (hypothalamic) congenital or acquired hypothyroidism. It is also approved for use as an adjunct to surgery and radioiodine therapy in the management of thyrotropin-dependent well-differentiated thyroid cancer.

According to the updated labeling, Tirosint-SOL can now be taken on an empty stomach 15 minutes before breakfast. Previously, it was recommended that the treatment be taken 30 minutes to 1 hour prior to breakfast. The update was based on study findings that showed there were no clinically significant differences in levothyroxine pharmacokinetics between Tirosint-SOL administered 15 minutes or 30 minutes before a high-fat, high-calorie meal (about 800-1000 kcal, 50% fat).

The updated labeling also includes the removal of proton pump inhibitors (PPI) as a drug interaction. Findings from a study evaluating Tirosint-SOL and the PPI omeprazole showed no interaction regardless of the timing of PPI administration. 

Tirosint-SOL is available in 15 strengths: 13mcg/mL, 25mcg/mL, 37.5mcg, 44mcg, 50mcg/mL, 62.5mcg, 75mcg/mL, 88mcg/mL, 100mcg/mL, 112mcg/mL, 125mcg/mL, 137mcg/mL, 150mcg/mL, 175mcg/mL, and 200mcg/mL. 

“The availability of this liquid oral levothyroxine formulation, which is not affected by proton pump inhibitors and can be taken just 15 minutes before breakfast, is a real plus for hypothyroid patients and health care practitioners,” said Michael Scully, Head of Commercial Operations, IBSA USA. “These new label changes reinforce Tirosint-SOL’s position as a simple, convenient, and clean LT4 therapy with only three ingredients.”

Geir Hoff, MD, PhD, from the University of Oslo in Norway, and colleagues examined long-term follow-up of a randomized trial of thyroidectomy plus medical management versus medical management alone for patients with Hashimoto disease, with persistent symptoms despite adequate thyroid hormone substitution. At inclusion, control patients were given the option of having surgery at 18 months after enrollment, depending on the trial results. Participants were followed up at 5 years in the intervention group and until date of surgery in the control group.

At baseline, 72 and 74 patients were included in the surgery and control groups, respectively. The researchers found that the positive treatment effect on the general health score, seen after 18 months, was maintained through 3-year follow-up. The improved score remained at the same level in the intervention group during 5-year follow-up. For the other Short Form-36 Health Survey domains and for total fatigue and chronic fatigue, results were similar. Short-term or longer-lasting complications occurred in 23 patients, including 6 with recurrent laryngeal nerve paralysis and 12 with hypoparathyroidism.

“Total thyroidectomy was shown to have a beneficial and long-lasting effect up to five years for patients with Hashimoto disease and persistent symptoms in an unblinded randomized clinical trial but with a substantially higher risk for complications than postulated at the beginning of the study,” the authors write.

Abstract/Full Text (subscription or payment may be required)