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FDA Rejects Takeda’s Submission to Continue Marketing Natpara for Hypoparathyroidism

March 23, 2022

Japanese pharmaceutical Takeda said it has received a Complete Response Letter from the U.S. Food and Drug Administration in response to the Prior Approval Supplement submitted in August 2021 to address the potential for rubber particulate formation that led to the U.S. Natpara recall in September 2019.

The CRL indicates that the FDA has completed its review of the Natpara submission and determined that it cannot be approved in its present form. Takeda is evaluating the details of the CRL to determine next steps. In the meantime, the company says it is disappointed to inform the hypoparathyroidism community that Natpara’s commercial return in the United States is indefinitely delayed.

Natpara was initially approved in May 2017 for the treatment of chronic hypoparathyroidism. Hypoparathyroidism is a rare condition in which the parathyroid glands fail to produce sufficient amounts of parathyroid hormone or the parathyroid hormone produced lacks biologic activity. The hormones are involved in numerous vital processes including regulating heart rate, body temperature, and blood pressure as well as cell differentiation and growth and also in modulation of several metabolic processes. Parathyroid hormone (along with vitamin D and the hormone calcitonin, which is produced by the thyroid gland) plays a role in regulating the levels of calcium and phosphorus in the blood and in determining bone growth and bone cell activity.

Due to a deficiency of parathyroid hormone, individuals may exhibit abnormally low levels of calcium in the blood (hypocalcemia) and high levels of phosphorus (hyperphosphatemia). Hypocalcemia can cause a variety of symptoms including weakness, muscle cramps, excessive nervousness, headaches, and/or uncontrollable twitching and cramping spasms of certain muscles such as those of the hands, feet, arms, legs, and/or face. Numbness and tingling around the mouth and in the fingers and toes can also occur. The most common cause of hypoparathyroidism is damage to or removal of the parathyroid glands due to surgery for another condition. Hypoparathyroidism can also be caused by an autoimmune process or can occur for unknown reasons or in association with a number of different underlying disorders. In rare cases, hypoparathyroidism may occur as a genetic disorder. Such cases can include familial hypoparathyroidism, which may be inherited as an autosomal recessive, autosomal dominant or X-linked recessive trait.

Because there are no other FDA-approved treatment alternatives, Takeda says it intends to provide patients who are enrolled in the Natpara Special Use Program (SUP) with continued access to therapy free of charge, in accordance with regulatory oversight and under the discretion of the FDA, until a commercial product is available.

The company says it will continue to work on the separate supply challenges surrounding protein particle formation that that it has already made known and which it says are unrelated to the Prior Application Supplement and the recall.

Author: Rare Daily Staff

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