RARE Daily

FDA Grants Rare Pediatric Disease Designation to Oxular for Eye Therapy and Italfarmaco for DMD Therapy

October 12, 2020

Rare Daily Staff

The U.S. Food and Drug Administration granted Rare Pediatric Disease designation to U.K. biotech Oxular’s OXU-003 for the treatment of retinoblastoma, and to Italian biotech Italfarmaco’s givinostat for the treatment of Duchenne muscular dystrophy.

Retinoblastoma is a rare form of eye cancer that develops in the retina, usually in early childhood, typically before the age of five. The most common first sign of retinoblastoma is a visible whiteness in the pupil called “cat’s eye reflex” or leukocoria. Other signs and symptoms of retinoblastoma include crossed eyes or eyes that do not point in the same direction (strabismus), a change in eye color, redness, soreness, or swelling of the eyelids, and blindness or poor vision in the affected eye or eyes.

Retinoblastoma is often curable if it is diagnosed early before it spreads to other parts of the body. Current treatment options include systemic chemotherapy and intra-arterial chemotherapy, which are very invasive procedures and require specialized facilities and hospital stay, and can lead to significant side effects for patients, including neurocognitive impairment, loss of vision and hearing, and life-threatening infections (sepsis) from low blood counts (neutropenia).

Oxular’s OXU-003 program for the treatment of retinoblastoma consists of a proprietary anti-tumor drug that utilizes Oxular’s formulation and ocular administration technology to safely deliver a precise amount of drug adjacent to the primary ocular tumor. OXU-003 has been shown to be effective as a stand-alone therapy in preclinical models and is complementary with other agents currently used to treat retinoblastoma. Oxular’s minimally invasive local therapeutic approach is intended to be less risky compared to current treatments, is expected to spare patients from related side effects while preserving vision and can be administered by an ophthalmic surgeons in standard operating rooms without the need of specialized equipment.

Duchenne muscular dystrophy (DMD) is a rare, fatal neuromuscular genetic disease that occurs in approximately one in every 3,500-5,000 males worldwide. DMD is caused by a change or mutation in the gene that encodes instructions for dystrophin. Symptoms of DMD usually appear in infants and toddlers. Affected children may experience developmental delays such as difficulty in walking, climbing stairs or standing from a sitting position. As the disease progresses, muscle weakness in the lower limbs spreads to the arms, neck and other areas.

Most patients require full-time use of a wheelchair in their early teens, and then progressively lose the ability to independently perform activities of daily living such as using the restroom, bathing and feeding. Eventually, increasing difficulty in breathing due to respiratory muscle dysfunction requires ventilation support, and cardiac dysfunction can lead to heart failure. The condition is universally fatal, and patients usually succumb to the disease in their twenties.

Italfarmaco’s givinostat is a proprietary histone deacetylase (HDAC) inhibitor in late stage development to treat boys with DMD. HDACs are enzymes that prevent gene translation by changing the three-dimensional folding of DNA in the cell. Studies show that Duchenne patients have higher than normal HDAC activity, which may prevent muscle regeneration, and also trigger inflammation. In the company’s clinical study in DMD, boys aged 7 to less than 11 years, givinostat was observed to slow disease progression, significantly increase muscle mass and reduce the amount of fibrotic tissue. givinostat treatment also significantly reduced muscle tissue necrosis and fatty replacement, two additional parameters related to disease progression.

In April 2020, Italfarmaco announced that interim data from the EPIDYS phase 3 clinical trial revealed slower disease progression in boys treated with givinostat and on a stable regimen of steroids. With trial enrollment completed, the last patient is expected to complete the 72-week treatment period in the first quarter of 2022, and the company expects to report topline data from the trial in June 2022.

The FDA grants Rare Pediatric Disease designation for serious or life-threatening diseases with manifestations in individuals aged from birth to 18 years, including access to the FDA’s expedited review and approval process. The designation makes these experimental therapies eligible for a Rare Pediatric Disease Priority Review voucher upon approval of the therapy by the FDA.

The vouchers can be used to reduce the time of an FDA new drug approval review to six months from ten months. The vouchers are potentially lucrative because they are transferable. Most recently, Sarepta sold its priority review voucher to Vifor Pharma $111 million in February 2020.

The program was due to expire at the end of September with a drug that had been granted RPD designation prior to that date still eligible to receive the voucher if it receives final FDA approval before September 30, 2022.

On September 30, 2020, Congress provided a short-term extension of the Rare Pediatric Disease Priority Review Voucher Program. According to the current statutory sunset provisions, after December 11, 2020, FDA may only award a voucher for an approved rare pediatric disease product application if the sponsor has rare pediatric disease designation for the drug, and that designation was granted by December 11, 2020. After December 11, 2022, FDA may not award any rare pediatric disease priority review vouchers.

Going forward, requests for rare pediatric disease designation submitted will be reviewed in a timely manner but the FDA’s previous 60-day response time no longer applies.


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