Return of Takeda’s Parathyroid Hormone Injection Delayed Indefinitely

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Takeda faces yet another setback by the U.S. Food and Drug Administration for its parathyroid hormone, natpara. Natpara is intended to help patients navigate low blood calcium due to hypoparathyroidism.

In Sept. 2019, Takeda issued a U.S. recall of all natpara for injection due to a potential for rubber particulate stemming from the rubber septum of the natpara cartridge. During the 14-day treatment using the therapeutic, a rubber septum is punctured by a needle each day to deliver the daily dosage. The company stated that repeated puncturing could result in small rubber fragments detaching into the cartridge. The recall was classified as Class I due to the potential risk of rubber stopper clogging the needle, leading to under-dosing.

In response to the recall, Takeda submitted a Prior Approval Supplement (PAS) for natpara in Aug. 2021 to address the potential for rubber particulate formation. The submission proposed a device component change to include a new septum and a new needle.

Despite its efforts to rectify the issues with natpara, Takeda received a Complete Response Letter (CRL) from the FDA stating that the PAS could not be approved in its present form, delaying the commercial return of natpara indefinitely. In a statement, Takeda said it would be evaluating the details of the CRL to determine its next steps.

Although the therapeutic won’t be returning to the commercial market, Takeda intends to continue to provide patients who are enrolled in the natpara special use program continued access to the therapy free of charge with regulatory oversight and discretion provided by the FDA. The special use program was implemented following the recall of the drug in Sept. 2019 so that patients who were previously prescribed natpara could continue taking the drug because discontinuing it would cause potentially life-threatening complications.

In order to continue to supply the special use program patients, Takeda will also have to address separate supply challenges surrounding protein particle formation unrelated to the initial recall. In October 2020, the company released a statement detailing a near-term supply interruption related to unexpected manufacturing disruptions.

Hypoparathyroidism occurs when one or more of the parathyroid glands are underactive, which causes abnormally low calcium levels in the blood. The disease is generally caused by damage to the parathyroid glands due to surgery, autoimmune disease or a genetic disorder.

Natpara received approval from the FDA in September 2015 and became the first FDA-approved prescription parathyroid hormone that is taken alongside calcium and Vitamin D to control abnormally low levels of calcium in people with hypoparathyroidism. The drug works by helping the intestines to absorb calcium by activating Vitamin D, increasing the amount of calcium the kidneys reabsorb and releasing calcium from bones.

The approval was based on evidence from a trial of 124 adults who were diagnosed with established hypoparathyroidism. Primary objectives met during clinical trials included a reduction in baseline in the dose of Vitamin D by at least 50%, a reduction in the dose of oral calcium supplementation by at least 50% and an albumin-corrected total serum calcium concentration between 7.5 mg/dL and 10.6 mg/dL, putting patients in a normal calcium range.