The CEO's letter to stockholders from the 2003 Annual Report provides a good overview on the company:
Dear Stockholders:
I am very pleased to update you on our progress at Pharmacyclics. We have focused our resources on our late stage investigational product, Xcytrin® Injection (motexafin gadolinium), now in a pivotal Phase 3 trial. By initiating other clinical trials with Xcytrin in several cancer types, we have leveraged our clinical development strengths and increased the chances for success with this product. We have moved forward other compounds generated from our versatile technology platform that have produced promising results in early clinical and preclinical studies. And we have efficiently managed our cash.
During this year, we initiated enrollment in our pivotal Phase 3 SMART(Study of Neurologic Progression with Motexafin Gadolinium And Radiation Therapy) trial of Xcytrin in non-small cell lung cancer patients with brain metastases, (i.e., cancer that has spread to the brain from another part of the body).
The SMART trial was designed with input from a number of leading clinical experts and with substantial involvement of the FDA. The rationale for the design of the SMART trial was based on results of our recently completed 401-patient randomized controlled trial in brain metastases, published in the July 2003 issue of the Journal of Clinical Oncology, the official journal of the American Society of Clinical Oncology. Widely considered to be one of the most comprehensive and rigorous clinical studies ever performed in brain metastases, this trial demonstrated consistent benefit in several measurements of neurologic outcomes in patients with lung cancer receiving Xcytrin. We believe that the physicians participating in the study have demonstrated that Xcytrin has the potential to make a major impact in oncology.
Epidemiologic estimates for the year 2000 demonstrate that lung cancer was the most common cancer in the world, both in terms of incidence (1.2 million new cases worldwide, 164,000 new cases in the United States) and mortality (1.2 million deaths worldwide, 156,900 deaths in the United States). Moreover, lung cancer is expected to remain the leading cause of morbidity and mortality from cancer for decades to come. Unfortunately, newer therapies have not made a significant impact on mortality and patients with lung cancer continue to suffer serious morbidity. One of the most devastating of all cancer related complications is the development of brain metastases, which commonly occur in lung cancer patients. Up to 50% of patients with lung cancer will develop brain metastases. In our previous trial with Xcytrin, 46% of the patients with lung cancer had detectable brain metastases at the time of initial diagnosis of their lung cancer. Patients with brain metastases suffer dreadful neurologic and neurocognitive (ability to think and remember) problems that have a devastating impact on quality of life, family members and health care providers, and impose high costs on the health care system. In fact, clinical research has shown that patients fear the loss of neurologic and neurocognitive function more than any other potential problem associated with a serious illness. Imagine having an illness that leaves you unable to walk or communicate, or unable to recognize or remember your loved ones.
Pharmacyclics and a worldwide network of approximately 100 leading medical centers are now conducting the SMART trial intended to prove that Xcytrin improves neurologic and neurocognitive outcomes in patients with lung cancer. The SMART trial was reviewed and approved through the FDA Special Protocol Assessment procedure. The SMART trial is a pivotal trial designed to lead to approval for Xcytrin to prolong time to neurologic progression in patients with brain metastases from lung cancer, should the trial be successful. We and the participating clinical investigators are excited about this trial because of the previous results obtained with Xcytrin for this indication and the knowledge and expertise that we have established in clinical development, brain metastases clinical research and neurologic outcomes assessments. Enrollment in the SMART trial is on track for planned completion by the end of calendar 2004.
Our experience and confidence in Xcytrin, the body of published scientific and clinical evidence that now exists for this agent, and the interest shown from numerous clinicians have encouraged us to expand its potential uses to a variety of other cancers. Xcytrin is a unique product opportunity in oncology with the potential to be used in a wide range of clinical situations and in a variety of cancers. We have launched several Phase 1 and 2 clinical trials evaluating Xcytrin either as a single agent or in combination with antibodies, radiation and/or chemotherapy for many cancers including lung, head and neck, prostate, breast, ovarian, primary brain tumors and lymphomas and leukemias. Some of these studies will be generating clinical data in late 2003.
Beyond Xcytrin, our proprietary texaphyrin technology platform continues to exhibit remarkable versatility, allowing us to generate a diverse range of product candidates. In addition to oncology, our primary focus, we have applied our technology to the emerging area of vulnerable plaque, now known to be the most important cause of heart attacks. Antrin® (motexafin lutetium), our lead product candidate in this indication, has completed Phase 1 testing in patients with coronary artery disease. The results of this trial have been presented at major cardiology meetings and were recently published in the journal, Circulation. To our knowledge, Antrin is among the first products to be evaluated for treatment of vulnerable plaque and, consequently, is receiving a significant amount of interest from clinicians. Our strategy is to establish a corporate partnership for this drug with a major company focused on development and commercialization of innovative cardiovascular disease products. We currently maintain full worldwide rights to both Antrin and Xcytrin.
Antrin and Xcytrin are just two examples of the diverse applications of our technology platform. It allows us to design and produce drug candidates with novel biochemical properties by making slight modifications to chemical structure. In addition to Xcytrin for oncology and Antrin for atherosclerosis, texaphyrin molecules continue to show promise in other indications. Activity has been demonstrated in preclinical models of HIV and, most recently, in the progressive neurodegenerative disease Amyotrophic Lateral Sclerosis (ALS), often referred to as “Lou Gehrig’s disease.”
We have the human and financial resources to complete the development of Xcytrin, which remains our focus. We are efficiently managing our cash and believe that we can become a leading oncology company and can successfully commercialize novel oncology products that address serious unmet needs. Compounds in other areas will be licensed to partners when sufficient value has been created, while we focus our resources in oncology.
We embark upon the coming year with a clear vision and strategy for increasing stockholder value. I look forward to updating you on our progress this year as we move Xcytrin closer to market, expand its potential indications and leverage our versatile technology platform to address other important medical needs.
Richard A. Miller, M.D.
President and Chief Executive Officer |
