The US Food and Drug Administration (FDA) has granted both orphan drug designation and rare paediatric disease designation for Ignyta's lead product candidate entrectinib for the treatment of neuroblastoma.
"We are pleased that the FDA has provided us these designations, which highlight the potential for entrectinib to address unmet needs of patients with rare cancers," said Jonathan Lim, MD, Chairman and chief executive officer, of Ignyta. "Although Ignyta is intrinsically motivated to continue to aggressively pursue our clinical development programme for entrectinib in solid tumours for the benefit of adult and pediatric cancer patients everywhere, we are pleased that the incentives provided by these designations including the potential for seven years of marketing exclusivity and the potential to obtain a valuable Pediatric Disease Priority Review Voucher from the FDA - can potentially provide additional avenues for creating value for our stockholders."
Under the FDA's Orphan Drug Designation programme, orphan drug designation is granted by the FDA to novel drugs or biologics that treat rare diseases or conditions affecting fewer than 200,000 patients in the US The designation allows the drug developer to be eligible for a seven-year period of US marketing exclusivity upon approval of the drug, as well as tax credits for clinical research costs, the ability to apply for annual grant funding, clinical trial design assistance, and the waiver of Prescription Drug User Fee Act (PDUFA) filing fees.
Under the FDA's Pediatric Disease Priority Review Voucher programme, upon the approval of a qualifying new drug application (NDA) or biologics license application (BLA) for the treatment of a rare pediatric disease, the sponsor of such application would be eligible for a Pediatric Disease Priority Review Voucher that can be used to obtain priority review for a subsequent NDA or BLA. The FDA defines a "rare pediatric disease" as a disease that affects fewer than 200,000 individuals in the US primarily aged from birth to 18 years. The Priority Review Voucher may be sold or transferred an unlimited number of times.
Prior to approval, each drug marketed in the United States must go through a detailed FDA review process. In 1992, under PDUFA, the FDA agreed to specific goals for improving the review time of NDAs and BLAs and created a two-tiered system of review times - Standard Review and Priority Review. Standard Review can be accomplished in a ten-month time frame from the time the application is filed by the FDA, which typically occurs approximately 60 days following submission of the application. A Priority Review designation is given to drugs that offer major advances in treatment, or provide a treatment where no adequate therapy exists. The FDA goal for reviewing a drug with Priority Review status is six months from the time the application is filed by the FDA.
Entrectinib is a potent, novel, orally available, selective tyrosine kinase inhibitor of the Trk family of tyrosine kinase receptors (TrkA, TrkB and TrkC), ROS1 and ALK proteins. Entrectinib is designed as a targeted therapeutic candidate to treat patients with cancers that harbor activating alterations to TrkA, TrkB, TrkC, ROS1 or ALK. Entrectinib has demonstrated in vivo antitumor activity against various TrkA, ROS1 or ALK-driven mouse xenograft models of different human cancers, and has demonstrated oral bioavailability and been observed to efficiently cross the blood brain barrier in three animal species.
Entrectinib is currently in two phase I/II clinical trials, the STARTRK-1 trial and the ALKA-372-001 trial. The company presented interim results from the ALKA-372-001 study in September 2014 at the ESMO annual meeting. The interim findings at such date showed:No dose-limiting toxicities were observed, and only one Grade 3 or higher possibly drug-related adverse event was observed (Grade 3 fatigue, which subsided with dose reduction);Eight patients remained on active treatment across the three dosing schedules, with four patients having received 9 to 21 cycles of treatment;Entrectinib demonstrated a complete response in a patient with ROS1-positive non-small cell lung cancer (NSCLC);Entrectinib demonstrated five partial responses, in patients with three different cancer histologies (colorectal cancer, NSCLC and neuroblastoma) and in patients with each of TrkA, ROS1 and ALK alterations; and Entrectinib demonstrated prolonged stable disease in two patients: one with ALK-positive NSCLC and one with ROS1-positive pancreatic cancer.
In addition to neuroblastoma, Ignyta has filed applications with the FDA for orphan drug designation for entrectinib in multiple adult indications.