FDA Approves Thiola EC (tiopronin) for the Treatment of Cystinuria

Retrophin, Inc. announced that the U.S. Food and Drug Administration (FDA) has approved 100 mg and 300 mg tablets of Thiola EC (tiopronin), a new enteric-coated formulation of Thiola (tiopronin), to be used for the treatment of cystinuria, a rare inherited disorder that causes a buildup of cystine levels in the urine resulting in the formation of recurring cystine kidney stones. Thiola EC is expected to be available in July 2019.

"The approval of Thiola EC marks another step in our continued commitment to helping patients with cystinuria manage the threat of recurring cystine stones," said Eric Dube, Ph.D., chief executive officer of Retrophin. "This new formulation provides patients with the freedom to administer Thiola EC with or without food, an advancement over the original formulation which has limiting food restrictions, and also provides the potential to reduce the number of tablets necessary to manage cystinuria. We look forward to working with the cystinuria community as we make the new formulation available next month."

The recommended initial dosage of Thiola in adult patients is 800 mg per day and in clinical studies the average dose of Thiola was approximately 1,000 mg, or 10 pills per day. The original formulation of Thiola 100 mg is recommended to be administered at least one hour before or two hours after meals. Thiola EC 100 mg and 300 mg tablets are recommended to be administered with or without food.

"Thiola’s utility as the treatment of choice for cystinuria is well established. However, for certain patients, the challenges of administration one hour before or two hours after meals three times a day, coupled with a high pill burden, have been challenging," said Dr. David S. Goldfarb, Clinical Chief, Division of Nephrology at NYU Langone Health. "Having a new treatment option with the flexibility of dosing with or without food, as well as one that provides an opportunity for patients to take fewer pills, should meaningfully improve convenience and compliance."

Thiola EC tablets were approved through the 505(b)(2) regulatory pathway which allows the FDA to reference previous findings of safety and efficacy for an already-approved product, combined with reviewing findings from further studies of the product.

About Thiola EC (tiopronin)

Thiola EC (tiopronin) is indicated, in combination with high fluid intake, alkali, and diet modification for the prevention of cystine stone formation in adults and pediatric patients ≥20 kg with severe homozygous cystinuria, who are not responsive to these measures alone.

Important Safety Information

Contraindications:

Thiola EC is contraindicated in patients with hypersensitivity to tiopronin or any other components of Thiola EC.

Warnings and precautions:

Proteinuria: Proteinuria, including nephrotic syndrome and membranous nephropathy, have been reported with tiopronin use. Pediatric patients receiving >50 mg/kg of tiopronin per day may be at increased risk for proteinuria. Monitor patients for the development of proteinuria and discontinue therapy in patients who develop proteinuria.

Hypersensitivity Reactions: Hypersensitivity reactions (drug fever, rash, fever, arthralgia and lymphadenopathy) have been reported.

Adverse Reactions:

The most common adverse reactions (≥10%) are nausea, diarrhea or soft stools, oral ulcers, rash, fatigue, fever, arthralgia, proteinuria, and emesis.

Drug interactions:

Avoid alcohol consumption 2 hours before and 3 hours after taking Thiola EC.

Special populations:

Lactation: Breastfeeding is not recommended during treatment with Thiola EC.

Geriatric Use: Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function.

You may report negative side effects to Retrophin Medical Information at 1-877-659-5518, or to the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. Please see full Prescribing Information for Important Safety Information at thiola.com.

About Thiola

Thiola (tiopronin) is indicated, in combination with high fluid intake, alkali, and diet modification for the prevention of cystine stone formation in adults and pediatric patients ≥20 kg with severe homozygous cystinuria, who are not responsive to these measures alone.

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