STOCKHOLM - January 22, 2014. Aprea AB, a Karolinska Development portfolio company, today announced that the European Medicines Agency (EMA) has granted its drug candidate APR-246 orphan drug designation for the treatment of ovarian cancer. Aprea is currently conducting a Phase Ib/II trial of APR-246 in combination with standard of care chemotherapy in patients with relapsed platinum sensitive high-grade serous ovarian cancer.
APR-246 is an innovative, first-in-class, anti-cancer agent with the potential to restore p53 activity in patients where p53 is non-functional or mutated. “To the company’s knowledge, APR-246 is the only compound in clinical development that can restore normal function of the p53 protein and thereby induce efficient cancer cell death. The orphan drug designation offers significant benefits during the forthcoming development and commercialisation of this potentially ground-breaking treatment,” said Bruno Lucidi, CEO of Aprea and Karolinska Development.
APR-246 has previously been tested in a first-in-human dose finding study. Based on the results of the Phase I study as a single agent in a total of 32 patients, the safety and pharmacokinetic profile of APR-246 allows for combination with standard of care chemotherapy. Furthermore, preclinical ex vivo studies with human ovarian cancer cells treated with APR-246 in combination with chemotherapy showed clear synergistic effects of the two treatments combined.
Owing to the widespread occurrence of mutations in p53, the therapeutic approach of APR-246 may be applied in many types of cancers. The potential impact in ovarian cancer alone is substantial – currently, around 600,000 women are living with ovarian cancer worldwide. Approximately 60% of the ovarian cancer patients have an advanced stage disease at diagnosis, and among these patients, the 5-year survival rate is lower than 30%. Aprea’s ongoing Phase Ib/II study includes ovarian cancer patients that have relapsed from first-line chemotherapy where the median overall survival is 17 months.
Cancers develop and spread due to the malfunction of the cells’ normal growth control mechanisms. The cancer suppressing gene p53 is mutated in approximately 50% of all cancers, whereby cells lack functional p53 protein and the most important suicide mechanism is impaired. This allows for cancer cell survival and rapid tumor growth. Aprea has developed substances that can restore normal function to the p53 protein and thereby induce efficient cancer cell death and overcome resistance to antitumoral therapy.
Obtaining orphan drug designation for APR-246 in the European Union is an important regulatory milestone and also provides incentives to support development, including fee reductions and a ten year period of market exclusivity after product approval.
For further information, please contact:
Bruno Lucidi, CEO, Aprea AB
Phone: +46 (0)8 508 84 504, e-mail: bruno.lucidi@aprea.com
TO THE EDITORS
About Aprea AB
Aprea AB is a Swedish biotech company focusing on discovery and development of novel anticancer compounds targeting the tumor suppressor protein p53. The main owner of Aprea is KDev Investments AB, part of Karolinska Development AB (publ). The other main owners are Östersjöstiftelsen, Praktikerinvest and KCIF Co-Investment Fund KB. For more information, please visit www.aprea.com
About APR-246
APR-246 has been developed based on results from researchers at Karolinska Institutet, and has been shown to reactivate non-functional tumor suppressor protein p53 and induce programmed cell death in many human cancer cells. Preclinical studies have confirmed that APR-246 can activate mutated p53 and demonstrated single agent efficacy and very strong synergy with conventional anti-cancer agents in vitro and in vivo. A clinical Phase Ib/II study in hematological malignancies and prostate cancer has been completed, demonstrating a favorable safety profile and both biological and clinical responses. A Phase Ib/II proof-of-concept study in ovarian cancer patients carrying mutant p53 is currently ongoing.
About the PiSARRO trial
The Phase Ib/II trial is designed to evaluate the safety, efficacy, pharmacokinetics and pharmacodynamics of APR-246 in combination with carboplatin (AUC 5) and pegylated doxorubicin (30 mg/m2), a second line standard of care chemotherapy for relapsed platinum sensitive high grade serous ovarian cancer. The Phase Ib/II trial is a two-part study that will enroll approximately 180 patients. Part A is an open-label, multiple ascending dose study. The primary objectives of Phase Ib are to evaluate the safety and tolerability of APR-246 in combination with carboplatin and pegylated doxorubicin, and to confirm the dose of APR-246. Pending successful completion of this phase, Aprea expects to initiate Part B of the trial, which will be a randomized, controlled study investigating the safety and antitumor activity of APR-246 administered in combination with carboplatin and pegylated doxorubicin, compared with carboplatin and pegylated doxorubicin alone. Primary end point of Phase II will be Progression Free Survival (PFS). For details on the PiSARRO trial please visit: www.ClinicalTrials.gov.
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