Liproca® Depot is designed for focused treatment of localized prostate cancer. The product combines a proven anti-androgen flutamide, with LIDDS unique drug technology. Liproca® Depot injected directly into the prostate using a user applicator for providing a long acting anti-tumor effect. The dosage can be monitored during injection with ultrasound, increasing tumörspecificiteten and dose accuracy. The effect is supposed to deploy quickly than when flutamide is given in pill form and linger in about six months, while the risk of troublesome side effects is small and no hormonal side effects have been reported in clinical studies.
Liproca® Depot – Local treatment of prostate cancer.
With Liproca® Depot injection is supplied to a well-tested drug (2-hydroxy-flutamide) directly into the tumor area. Where it stays active substance and remains effective for up to six months. There are clinical data indicating that Liproca ® Depot has effect on tumor tissue, but the risk of side effects is significantly lower than current therapy.
An innovative product based on an established drug
Liproca® Depot contains the anti-androgenic substance 2-hydroxy-flutamide, which is the predominant and most active metabolite of flutamide. Flutamide (Eulexin®; Merck Co.) is the first global anti-androgen drug approved for the treatment of prostate cancer and is available in tablet form since a couple of decades. This form of systemic hormone therapy can often suppress cancer growth for a long time, but because the whole body is exposed to the drug, most patients of bothersome side effects that affect quality of life negatively. The patents for 2- flutamide and hydroxyflutamide has elapsed and the active substance can thus be freely used by LIDDS to develop a new and improved medical product with intellectual property rights.
LIDDS audience and processing segments
Liproca®Depot is a treatment that is applicable to a total of approximately 400,000 patients each year offered "active surveillance" or "symptom-driven treatment" of their prostate cancer. Liproca® Depot may be an option for patients who, for various reasons oppose surgery, radiation or pharmacological treatment. These patients have a local prostate cancer who are not so aggressive that it requires surgery or radiation. Patients are followed up with frequent PSA tests and prostate biopsies and currently receives no treatment at all, allowing many patients concern and anxiety for the cancer to become more aggressive. Since Liproca® Depot with its antiandrogenic and acting effect, may inhibit cancer cells for a long time can hopefully these patients with one or more treatments Liproca® Depot keep cancer in check and hopefully entirely avoid surgery or radiation with the associated risk of side effects. In the upcoming Phase IIb study is planned to be about sixty patients at the urology clinics in Canada and Scandinavia, will be included with the aim to evaluate the optimal dose of Liproca® Depot and its effect on various cancer markers. Pharmaceutical amount will be increased by up to 200 percent compared with the second part of the LPC-003. The continued clinical evaluation of Liproca® Depot for the treatment of prostate cancer will be regularly discussed with the relevant authorities.
Treatment Benefits Liproca® Depot
Injecting Liproca® Depot is done in much the same way as when taking tissue samples from the prostate associated with the diagnosis and mapping of local tumor spread. The progress can be followed on an ultrasound screen as the drug carrier providing ultrasound shadow and thus are clearly visible. It admits that Liproca® Depot can be dosed with high precision to the regions of the prostate gland where it has identified tumor centers. This allows the attending physician to avoid injecting drugs outside the tumor itself, which results in increased safety and efficacy. Liproca® Depot has been designed so that the drug initially released quickly for about two weeks "boost dose" and then slowly over about six months. The support material, which is based on calcium sulfate, is dissolved at the same rate as the release of the active drug substance and disappear completely, leaving no residues or degradation products left in the body. The drug carrier is tissue-friendly and does not cause troublesome foreign body reactions or enclosures. This allows for repeated treatment for a long time.
Expected product benefits
The goal is to Liproca® Depot to offer a new effective therapy with less time to power, lower frequency of side effects and therefore better quality of life. The high drug concentration in the tumor also hopes for a powerful effect and hopefully patients with one or more Liproca® Depot treatments, inhibit cancer tumor for a long time to surgery and radiation are not needed.
Completed clinical trials
The active ingredient of Liproca® Depot, 2-hydroxy-flutamide, a metabolite of flutamide. The drug flutamide is explicitly documented in clinical trials and has been used in health care around the world for decades. Liproca® Depot has been studied in three clinical studies in a total of 57 patients with localized prostate cancer. Detailed information about the different studies presented in the table below.
The continued path to market approval
LIDDS planning a larger Phase IIb study, the LPC-004, to determine the optimal dose for pivotal Phase III trial. The design of the Phase III program and the final regulatory strategy established following discussions with regulatory authorities in Europe and the United States. In the upcoming Phase IIb study, approximately sixty patients at the urology clinics in Canada and Scandinavia to conclude with the objective to evaluate the optimal dose of Liproca® Depot and effects in different cancer markers. Pharmaceutical The amount will depend on the size of the prostate to be increased by up to 200 percent compared with the second part of the LPC-003. An application for approval in the United States can be either based on a so-called 505 (b) (1) NCE (New Chemical Entity) or 505 (b) (2), previously known substance. In both cases, it is possible to base the safety documentation largely on the available documentation of flutamide. This is because 2-hydroxyflutamide is the active metabolite of flutamide. This means less documentation requirements with respect to the preklinsika documentation and lower costs. In the United States 505 (b) (1) and (2), 5 and 3 years of document protection. In Europe, there is the possibility that either the application under Article 8 (3) - ie a full dossier for a new substance or in Article 10 (3), a hybrid application. These opportunities correspond to the American possibilities for application. Even in Europe it is possible to base the safety documentation largely on published data, regardless of the type of application you choose. In Europe there are likely opportunity for both a so-called decentralized procedure (DCP) or a centralized procedure regarding the application procedure. The advantage of DCP greater control and security while the CP provides a direct approval in all European countries including Norway and Iceland.
The target indication for Liproca® Depot's patients treated with "Active Monitoring" or "Symptoms controlled treatment" in anticipation of curative treatment, surgery or radiation. The goal of treatment with Liproca® Depot will be to extend the time to curative treatment needs to be given, perhaps as long as the need for curative treatment fails. Today there are no drugs approved for treatment in this indication. Out a regulatory perspective, it is a possibility as the control group in a Phase III program which does not receive any active treatment. Swedish authorities, who belongs to the tone rewarding authorities in Europe have indicated that there is a basis to discuss "conditional approval" based on early results of a Phase III program, which since the approval awaiting more data (effect on survival).
LIDDS project plan for large-scale production of Liproca® Depot has been developed following discussions with authorities and external experts, and reviewed and verified by qualified consultants. It is from a commercial point of view positively that the manufacturing process is secured prior to Phase III program starts. In December 2015 LIDDS signed an agreement with Recipharm to develop a process for the commercial production of Liproca® Depot and for scaling before the manufacture of investigational product for the next study. Production transfer involves investment of production equipment for commercial scale and set of a production line, transfer and management of analytical methods for process control, release and stability control, and implementation of know-how and critical manufacturing steps.
Strategy for commercialization
LIDDS intends to seek cooperation with one or more pharmaceutical companies are already before the start of the Phase III program. In this way, LIDDS quickly obtain a positive cash flow, reduce its own investments in the clinical development program and eliminate the need to build a global marketing organization.