Uterine fibroids are benign hormone-sensitive tumors of uterine smooth muscle cells leading to heavy menstrual bleeding and pelvic pain. Ulipristal acetate (UPA) is an emerging medical treatment of fibroids with the potential to be used for long-term treatment. In this context, the present article summarizes UPA’s main clinical pharmacology and pharmacokinetic (PK) properties. Ulipristal acetate has good oral bioavailability and a half-life allowing one single oral administration per day for the management of fibroids. As a steroid, UPA is a substrate for cytochrome P450 (CYP) 3A4 but does not act as an inducer or inhibitor of the CYP system or transporter proteins. With the exception of drugs modulating CYP3A4 activity, risks of drug-drug interactions with UPA are unlikely. In conclusion, besides its pharmacodynamic characteristics, UPA shows favorable PK properties that contribute to a good efficacy-safety ratio for the long-term management of uterine fibroids in clinical practice.
© The Author(s) 2014.

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Lenvatinib is an oral, multiple receptor tyrosine kinase inhibitor. Preclinical drug metabolism studies showed unique metabolic pathways for lenvatinib in monkeys and rats. A human mass balance study demonstrated that lenvatinib related material is mainly excreted via feces with a small fraction as unchanged parent drug, but little is reported about its metabolic fate. The objective of the current study was to further elucidate the metabolic pathways of lenvatinib in humans and to compare these results to the metabolism in rats and monkeys. To this end, we used plasma, urine and feces collected in a human mass balance study after a single 24 mg (100 μCi) oral dose of (14)C-lenvatinib. Metabolites of (14)C-lenvatinib were identified using liquid chromatography (high resolution) mass spectrometry with off-line radioactivity detection. Close to 50 lenvatinib-related compounds were detected. In humans, unchanged lenvatinib accounted for 97 % of the radioactivity in plasma, and comprised 0.38 and 2.5 % of the administered dose excreted in urine and feces, respectively. The primary biotransformation pathways of lenvatinib were hydrolysis, oxidation and hydroxylation, N-oxidation, dealkylation and glucuronidation. Various combinations of these conversions with modifications, including hydrolysis, gluthathione/cysteine conjugation, intramolecular rearrangement and dimerization, were observed. Some metabolites seem to be unique to the investigated species (human, rat, monkey). Because all lenvatinib metabolites in human plasma were at very low levels compared to lenvatinib, only lenvatinib is expected to contribute to the pharmacological effects in humans.

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To evaluate the treatment effects, safety and pharmacokinetics of enzalutamide in Japanese patients.
This was a post-hoc analysis of the phase 3, double-blind, placebo-controlled PREVAIL trial. Asymptomatic or mildly symptomatic chemotherapy-naïve patients with metastatic castration-resistant prostate cancer progressing on androgen deprivation therapy were randomized one-to-one to 160 mg/day oral enzalutamide or placebo until discontinuation on radiographic progression or skeletal-related event and initiation of subsequent antineoplastic therapy. Coprimary end-points were centrally assessed radiographic progression-free survival and overall survival. Secondary end-points were investigator-assessed radiographic progression-free survival, time to initiation of chemotherapy, time to prostate-specific antigen progression, prostate-specific antigen response (≥50% decline) and time to skeletal-related event.
Of 1717 patients, 61 were enrolled in Japan (enzalutamide, n = 28; placebo, n = 33); hazard ratios (95% confidence interval) of 0.30 for centrally assessed radiographic progression-free survival (0.03-2.95), 0.59 for overall survival (0.20-1.8), 0.46 for time to chemotherapy (0.22-0.96) and 0.36 for time to prostate-specific antigen progression (0.17-0.75) showed the treatment benefit of enzalutamide over the placebo. Prostate-specific antigen responses were observed in 60.7% of enzalutamide-treated men versus 21.2% of placebo-treated men. Plasma concentrations of enzalutamide were higher in Japanese patients: the geometric mean ratio of Japanese/non-Japanese patients was 1.126 (90% confidence interval 1.018-1.245) at 13 weeks. Treatment-related adverse events grade ≥3 occurred in 3.6% of enzalutamide- and 6.1% of placebo-treated Japanese patients.
Treatment effects and safety in Japanese patients were generally consistent with the overall results from PREVAIL.
© 2016 The Authors. International Journal of Urology published by John Wiley & Sons Australia, Ltd on behalf of the Japanese Urological Association.

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On March 30, 2016 Amal Therapeutics (Amal) reported that they have completed CHF 3 million (EUR 2.75 million) Series A financing round with Boehringer Ingelheim Venture Fund (BIVF) as cornerstone investors (Press release, Boehringer Ingelheim, MAR 29, 2016, View Source [SID:1234510134]). VI Partners and High-Tech Gründerfonds also participated in the round which will help progress Amal’s cancer vaccines.

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Amal Therapeutics is a Swiss biotech company developing and progressing therapeutic cancer vaccines. The company will use the funds to progress the preclinical development of its lead vaccine (ATP124) for colorectal cancer and to further develop its KISIMA technology platform for therapeutic tumor vaccination. This novel technology is able to generate potent long lasting anti-tumor immunity and avoid tumor immune escape.

Dr. Frank Kalkbrenner from the Boehringer Ingelheim Venture Fund and Dr. Frank Hensel from the High-Tech Gruenderfonds will join the Board as Board Observers. Dr. Diego Braguglia from VI Partners will also become a member of Amal’s Supervisory Board.

Dr. Madiha Derouazi, CEO and founder of Amal Therapeutics said: "This Series A investment recognizes the potential of the KISIMA technology platform and the value of our scientific assets. We are now in a position to rapidly progress our lead vaccine, ATP124, for colorectal cancer into the clinic and continue to develop our pipeline in other cancer indications. I look forward to working with the Board to make Amal Therapeutics a leading innovator in the field of immunotherapies".

Dr. Knut Elbers, Boehringer Ingelheim Venture Fund representative on Amal’s Board added: "Dr. Derouazi’s dedicated leadership and scientific expertise allowed us to assemble a group of outstanding scientists to show proof-of-principle in a series of pre-clinical tumor studies. We are confident that Amal’s KISIMA technology could revolutionize the peptide-based cancer vaccine field – bringing an exciting new technology to the patient".

Dr. Braguglia, VI Partners: "We believe that the KISIMA technology is superior to many other tumor vaccine technologies, both as a stand-alone treatment and in combination with other vaccines or immuno-oncology treatment modalities. I’m pleased to be joining the current seasoned investors and support the team of Amal in moving its technology into the clinic".

Amal’s vaccines combine a Cell Penetrating Peptide (CPP) with a multi-antigenic chimeric cargo with various CD8+ and CD4+ epitopes and a constitutive activator of dendritic cells, enabling them to simultaneously stimulate multi-epitopic cytotoxic T cell-mediated immunity, induce helper T (Th) cells and promote immunological memory.

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