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Pharmacyclics Receives Special Protocol Assessment Agreement From FDA For Pivotal Phase 3 Trial Of Xcytrin
Jan. 7, 2003
Pharmacyclics, Inc. today announced that the U.S. Food and Drug Administration (FDA) has completed a Special Protocol Assessment (SPA) for the company´s pivotal Phase 3 trial of Xcytrin(R) (motexafin gadolinium) Injection for the potential treatment of lung cancer patients with brain metastases (i.e., lung cancer that has spread to the brain from another part of the body).
SPA, which was mandated by the FDA Modernization Act of 1997 and was first implemented in May 2002, provides for sponsors to receive official FDA evaluation, guidance and agreement on pivotal trials that will form the basis for final approval. This written agreement is binding.
"Through the Special Protocol Assessment process, the FDA has approved of and agreed to the approvability of the trial´s primary endpoint, time to neurologic progression, as well as our trial design and biostatistical analysis," said Richard A. Miller, M.D., president and chief executive officer of Pharmacyclics. "We have worked very closely with the agency over the past several months to design an optimal trial and we are confident in its potential for success."
This randomized controlled study, known as the SMART (Study of Neurologic Progression with Motexafin Gadolinium And Radiation Therapy) trial, is now underway and will enroll about 550 patients at over 100 leading medical centers in the United States, Canada, Europe and Australia. It will compare the effects of whole brain radiation therapy (WBRT) alone to WBRT plus Xcytrin in lung cancer patients with brain metastases. The primary efficacy endpoint will be time to neurologic progression as determined by a blinded events-review committee. Survival and neurocognitive function will also be assessed as secondary endpoints of the trial.
The SMART trial was designed by Pharmacyclics, together with leading experts in medical and radiation oncology. The design incorporates important information learned from a previous large randomized Phase 3 trial, which demonstrated Xcytrin, when added to WBRT, significantly prolonged time to neurologic progression and, as assessed by the clinical investigators, decreased deaths due to brain tumor progression in patients with brain metastases from lung cancer.
"The primary goal of treating patients with brain metastases is to slow or prevent neurologic progression," added Dr. Miller. "Our previous randomized trial demonstrated that Xcytrin provided neurologic benefit, as assessed by several criteria, to lung cancer patients with brain metastases. Lung cancer patients have distinct clinical characteristics and frequently develop brain metastases early in the course of their disease, often before the cancer relapses elsewhere or becomes too widespread. By evaluating Xcytrin in lung cancer patients in this trial, we believe we can most clearly demonstrate its clinical benefit."
About Xcytrin
Xcytrin is the first of a new class of drugs called texaphyrins, which selectively accumulate in cancer and other diseased cells based on their unique biochemical features, and disrupt cellular metabolism. By interfering with the flow of energy, Xcytrin prevents cancer cells from repairing damage caused by the effects of radiation and chemotherapy without increasing damage to normal tissue. Xcytrin is paramagnetic, and when localized in cancer cells, produces an enhancement of the MRI signal, which can be used to image the tumor.
About Brain Metastases
Brain metastases is one of the most common conditions treated with radiation therapy. There are about 150,000 to 170,000 new cases per year in the United States, and the incidence is increasing. The most common cause of brain metastases is lung cancer, affecting up to 90,000 patients.
Brain metastases occur when cancer cells spread to the brain and grow, causing major neurologic complications and, in most cases, death. Patients with brain metastases usually suffer serious deterioration of neurologic and neurocognitive function such as loss of short-term memory, compromised verbal skills and fine motor coordination, and reduction in cognitive performance. Most patients with brain metastases have multiple lesions and are not candidates for surgical resection or radiosurgery. The goal of whole brain radiation therapy is to reverse or prevent neurological deterioration and prevent death due to tumor progression in the brain.