FDA Roundup: New Indication for Ayvakit, OTC Switch

A new indication, a nonprescription switch, a recall, and new guidances round out this week’s FDA news.

New indication for Ayvakit is approved. The FDA has approved Ayvakit (avapritinib) to treat adult patients with advanced systemic mastocytosis (SM), including patients with aggressive systemic mastocytosis and mast cell leukemia. Patients can now receive a targeted therapy designed to potently and selectively inhibit D816V mutant KIT, the central driver of the disease.

Systemic mastocytosis is a rare hematologic disorder that results in excess mast cells in the skin, bone marrow, digestive tract, or other organs, which can lead to severe inflammation and organ damage. Median survival is 41 months in aggressive systemic mastocytosis.

The approval was based on the phase 1 EXPLORER trial and phase 2 PATHFINDER trial. The overall response rate in all evaluable patients in both trials combined was 57%, with 28% complete remissions and 28% partial remissions. The median duration of response was 38.3 months and the median time to response was 2.1 months. The most common adverse reactions (incidence ≥ 20%) in patients with advanced systemic mastocytosis were edema, diarrhea, nausea and fatigue/asthenia.

This application was granted priority review, breakthrough designation, and orphan drug designation.

Ayvakit, developed by Blueprint Medicines Corp. located in Cambridge, Mass., was approved in January 2020 for the treatment of adults with unresectable or metastatic gastrointestinal stromal tumor (GIST).

OTC antihistamine is approved. The FDA has approved the nonprescription nasal antihistamine Astepro (azelastine hydrochloride nasal spray, 0.15%) for seasonal and perennial allergic rhinitis for adults and children six years of age and older.

This approval is a first-in-class switch for a nasal antihistamine and is considered a partial switch because the 0.1% strength will remain prescription based.

The FDA granted the approval of nonprescription Astepro to Bayer Healthcare. Astrepro will be available in the first quarter of 2022, according to a company statement.

FDA accepts NDA for next-generation Tyvaso. The FDA has accepted for priority review a new drug application for Tyvaso DPI (inhaled treprostinil) for the treatment of pulmonary arterial hypertension (PAH) and pulmonary hypertension associated with interstitial lung disease (PH-ILD). The agency’s review is expected to be completed by October 2021.

Tyvaso DPI incorporates a dry powder formulation of treprostinil and the Dreamboat inhalation device technology. The next-generation product was developed in a collaboration by MannKind Corp. in Westlake Village, Calif., and United Therapeutics in Silver Spring, M.D.

Tyvaso is available in an inhalation solution to treat patients with PAH. Data from the BREEZE clinical study demonstrated safety and tolerability of Tyvaso DPI in patients with PAH transitioning from Tyvaso Inhalation Solution. A separate study in healthy volunteers demonstrated comparable treprostinil exposure between Tyvaso DPI and Tyvaso Inhalation Solution.

The DPI inhalation technology is also used in Mannkind’s Afrezza (insulin human) Inhalation Powder, which was approved by the FDA in 2014.

MannKind and United Therapeutics are also developing BluHale, a Bluetooth-connected accessory for the Tyvaso DPI inhaler with a companion mobile application intended to help patients track information about their inhaler use.

Rare disease therapy gets fast track designation. The FDA has granted fast track designation to AT-007 for the treatment of galactosemia, a rare metabolic disease. Applied Therapeutics, the developer of AT-007 plans to submit an New Drug Application (NDA) in the third quarter of this year.

AT-007 reduced plasma galactitol levels compared with placebo in adults with galactosemia in a phase 2 registrational trial; it is currently being studied in a registrational trial in children ages 2-17 with galactosemia. The FDA has previously granted both orphan drug and pediatric rare disease designations for the treatment of galactosemia.

Two lots of metformin are recalled. Viona Pharmaceuticals is voluntarily recalling two lots of metformin hydrochloride extended-release tablets, USP 750 mg. The two lots have been found to contain levels of nitrosodimethylamine (NDMA) impurities above acceptable daily limits. This product was manufactured by Cadila Healthcare in Ahmedabad, India, in November 2019, for U.S. distribution by Viona Pharmaceuticals.

NDMA is classified as a probable human carcinogen based on results from laboratory tests.

To date, neither Viona Pharmaceuticals nor Cadila Healthcare have received any reports of adverse events related to this recall.

Metformin is used improve blood glucose control in adults with type 2 diabetes.

Final guidance issued for breast cancer drug development. The FDA has issued a final guidance for developing therapies for premenopausal women with breast cancer. This guidance includes recommendations regarding the inclusion of premenopausal women, as defined by serum hormonal levels, in breast cancer clinical trials.

Specifically, the guideline recommends that stratification based on menopausal status may be appropriate for safety and efficacy evaluation. Additionally, the guidance says sponsors should collect data on bone health, cardiac health, and other clinical effects. Regulators said enrollment in trials should reflect the racial and ethnic diversity of this patient population to support the assessment of short- and long-term effects of these therapies across clinically relevant subgroups of patients.

Draft guidance is issued for assessing patient report outcomes. The FDA has issued a draft guidance document, “Core Patient-Reported Outcomes in Cancer Clinical Trials,” which, when finalized, will provide recommendations on which patient-reported outcomes (PRO) concepts to measure in cancer clinical trials.

The guidance addresses how to incorporate assessment of PRO in clinical trials of drugs and biological products that are intended to support product labeling describing anti-tumor activity in patients with cancer.

“The FDA’s Oncology Center of Excellence has undertaken a sustained effort to identify methods to rigorously collect patient-reported outcomes in cancer clinical trials. We’ve been engaging with patients and outcomes research experts through a series of public workshops and publications on which outcomes to measure, how frequently to assess them, and the tools available to do so,” Richard Pazdur, M.D., director of the FDA’s Oncology Center of Excellence, said in a statement.