Twenty-five to 30 million patients in the United States are living with a rare disease; this staggering number underscores a simple, yet little-known fact: the incidence of rare diseases is low, but prevalence remains high.
Despite many advances made in the fight against rare diseases, gaps remain when it comes to improving patient care—for some conditions, there are no safe or effective treatments available to patients to improve their quality of life.
The US Food and Drug Administration (FDA) Office of Orphan Products Development is dedicated to advancing the evaluation and development of products—drugs, biologics, or devices—that demonstrate potential in the diagnosis and/or treatment of rare diseases.
The following is a list of recent designations granted by the FDA from this past week that is working to further expand the collective arsenal against rare diseases:
Orphan Drug Designation Granted to CLN2 Form of Batten Disease, RGX-181
The FDA has granted an orphan drug designation to REGENXBIO Inc’s RGX-181 for the treatment of late-infantile neuronal ceroid lipofuscinosis type 2 (CLN2) disease, 1 of the most common forms of Batten disease caused by mutations in the tripeptidyl peptidase 1 (TPP1) gene.
"CLN2 disease is an extremely debilitating disease in children with no cure and limited treatment options,” said Kenneth T. Mills, President and CEO of REGENXBIO, in a recent statement. "We believe RGX-181 has the potential to correct the underlying genetic condition, halt progression and address many of the serious and life-threatening symptoms of CLN2 disease. Receiving an orphan drug designation from the FDA signifies our continued progress and commitment to develop RGX-181 as a potential one-time treatment for children with CLN2 disease."
Engineered to use REGENXBIO's NAV AAV9 vector, RGX-181 delivers the TPP1 gene directly to the central nervous system (CNS). Consequently, the 1-time treatment may induce sustained levels of TPP1, the enzyme deficient in pediatric patients with CLN2.
An investigational new drug (IND) application for RGX-181 is anticipated to be submitted by REGENXBIO to the FDA in 2019. If accepted, the application will enable the initiation of a first-in-human clinical trial.
FDA Accepts NDA for a New Formulation of Tiopronin for the Treatment of Cystinuria
The FDA has accepted Retrophin, Inc’s new drug application (NDA) for a new formulation of tiopronin (Thiola) in the treatment of cystinuria. Currently, the drug has a Prescription Drug User Fee Act (PDUFA) date set for June 30, 2019.
“We know that living with a rare kidney disorder like cystinuria can be a challenge, so we have worked with the patient, caregiver, and medical communities over the past several years to identify ways we can further enhance tiopronin,” said Stephen Aselage, chief executive officer of Retrophin, in a recent statement. “The acceptance of this NDA for review is an important milestone as we continue efforts to fulfill our ongoing commitment to support patients with cystinuria and deliver a new, more patient-friendly formulation of tiopronin.”
Tiopronin tablets are indicated for patients with severe homozygous cystinuria with urinary cystine >500 mg/day; who are resistant to treatment with conservative measures of high fluid intake, alkali, and diet modification; or who have adverse reactions to d-penicillamine. Their use is indicated for the prevention of cystine (kidney) stone formation in this patient population.
Fast Track Designation Granted to Pachyonychia Congenita Treatment, PTX-022
The FDA granted a fast track designation to Palvella Therapeutics, Inc’s PTX-022 for the treatment of pachyonychia congenita, a rare and lifelong monogenic disease that is chronically debilitating due to increased skin fragility and impaired skin barrier function on the plantar aspects of the feet.
Difficulty with ambulation is often experienced by patients, requiring the use of ambulatory aids or alternative forms of mobility, such as crawling.
“We’ve heard from PC patients, who struggle to walk while experiencing extreme pain, that 1 step can truly make all of the difference in their lives,” said Wes Kaupinen, president and chief executive officer of Palvella, in a recent statement. “The FDA’s decision to grant a fast track designation for PTX-022 is a positive step for our partners at PC Project and for Palvella in our shared ambition to accelerate the development of this important therapy.”
PTX-022 uses Palvella’s QTORIN technology, which uses a highly specific composition of excipients that enables the distribution of mTOR inhibitors into the basal keratinocytes. This function harbors the primary defects in pachyonychia congenita, which are the mutant keratin genes. QTORIN is engineered to further enable drug penetration into the reticular dermis, the location where neovascularization and inflammatory components of the pachyonychia congenita pathology manifest.
“The recognition by the FDA of the potential of PTX-022 to treat pachyonychia congenita builds upon the compelling scientific rationale and the encouraging early human clinical results seen with rapamycin in the treatment of PC,” added Joyce M. Teng, MD, PhD, clinical professor of dermatology and pediatrics at Stanford University School of Medicine. “I look forward to working closely with the Palvella team as we move expeditiously to advance PTX-022 into a phase 2/3 clinical study.”
Orphan Drug Designation Granted to AlphaMedix for the Treatment of Neuroendocrine Tumors
The FDA has granted an orphan drug designation to RadioMedix Inc and Orano Med’s AlphaMedix for the treatment of neuroendocrine tumors (NETs).
A 212Pb-labeled somatostatin analogue used for the targeted alpha therapy of neuroendocrine tumors, AlphaMedix delivers cytotoxic load of alpha-emitters to SSTR-overexpressing neuroendocrine tumors. Alpha emitters can cause irreversible damage to the cancer cells since they are highly energetic radioactive particles.
"TAT has brought new hope to our patients with cancer, and the range of available therapies in this area will only increase in the near future. We are pleased to conduct the first TAT clinical trial in the U.S. for neuroendocrine cancers, with the aim of registration of the drug,” said Ebrahim S. Delpassand, MD, CEO of RadioMedix and medical director of the clinical studies, in a recent statement.
A phase 1 clinical trial evaluating the safety and preliminary efficacy of AlphaMedix was launched in February of 2018 (2018 (NCT03466216). Patients are currently being recruited at the Excel Diagnostics and Nuclear Oncology Center in Houston, Texas.
“We are excited about the progress of our dose escalation studies of AlphaMedix,” reiterated Izabela Tworowska, PhD, CSO of RadioMedix.