Paclical (micellar paclitaxel) / Vivesto, HLB Bio Group, taiba - LARVOL DELTA

Polycaprolactone - Vitamin E TPGS micelles for delivery of paclitaxel: In vitro and in vivo evaluation. (PubMed, Int J Pharm X) - "Pharmacokinetics of PTX as part of PCL-TPGS showed a significant increase in its volume of distribution compared to PTX conventional formulation, Ebetaxel, which is in line with what was reported for clinical nano formulations of PTX, i.e., Abraxane, Genexol-PM, or Apealea. The findings of our studies indicate a significant potential for PCL-TPGS micelles to act as an effective system for solubilization and delivery of PTX."

Journal • Preclinical • Breast Cancer • Oncology • Solid Tumor

Vivesto and Elevar seek to transfer Elevar's Apealea rights and obligations to a third party (Market Screener) - "Vivesto AB...has been informed that Elevar Therapeutics Inc., which holds the rights to commercialize Vivesto’s anticancer product Apealea, intends to transfer its rights and obligations to a third party. A transfer of rights and obligations would require Vivesto’s consent, and no such consent has been given yet."

Licensing / partnership • Oncology

"#Vivesto announces Inceptua decision to withdraw #MarketAuthorizationApplication for #Apealea® in Switzerland https://t.co/dvmBoZq4SM" (@1stOncology)

Vivesto Sublicensee To Cancel Swiss Regulatory Application For Cancer Drug (Market Screener) - "Vivesto...said Wednesday that Inceptua decided to retract its marketing authorization application for cancer therapy Apealea filed with the Swiss Agency for Therapeutic Products, or Swissmedic, amid clinical data concerns. Noting its plan to reject the application, Swissmedic is of the view that the clinical data did not establish a positive benefit-risk balance for the drug. Meanwhile, the companies do not intend to commence additional clinical studies to secure approval in Switzerland for now, citing commercial reasons."

Non-US regulatory • Fallopian Tube Cancer • Gynecologic Cancers • Oncology • Ovarian Cancer • Peritoneal Cancer

"#Vivesto notes the launch of #Apealea® in Germany by #Inceptua https://t.co/CFYUOUGXns" (@1stOncology)

Inceptua receives approval of marketing authorization transfer of Apealea (paclitaxel micellar) for the treatment of ovarian cancer (Microbioz India) - “Inceptua Group…announces that the European Commission (EC) and the UK Medicines and Healthcare products Regulatory Agency (MHRA) has approved the transfer of the marketing authorization for Apealea® (paclitaxel micellar) from Oasmia Pharmaceutical AB to Inceptua AB. Apealea is approved in combination with carboplatin for the treatment of adult patients with first relapse of platinum-sensitive epithelial ovarian cancer, primary peritoneal cancer and fallopian tube cancer.”

European regulatory • Fallopian Tube Cancer • Gynecologic Cancers • Oncology • Ovarian Cancer • Peritoneal Cancer

Nanoparticle micellar formulation of paclitaxel in combination with carboplatin for women with recurrent platinum sensitive ovarian cancer (OAS07-OVA): Overall survival results of a phase 3 randomized trial. (ASCO 2018) - "2008-002668-32 Background: The primary objective in the pivotal trial OAS-07OVA was reached and it was demonstrated that Paclical, a nanoparticle micellar formulation of paclitaxel (Oasmia Pharmaceutical AB) is non-inferior to Cremophor-EL Paclitaxel in terms of progression free survival (PFS) in the treatment of recurrent platinum-sensitive ovarian, fallopian tube or peritoneal carcinoma. Paclical is non-inferior to Taxol with respect to OS and PFS for patients with recurrent platinum-sensitive ovarian cancer. Even though the pivotal study was not designed to show superiority, subgroup analyses show a consistent tendency of favor for Paclical in terms of OS and PFS indicating a benefit for the Paclical group."

Clinical • Combination therapy • P3 data • Ovarian Cancer

"#Oasmia transfers Nordic commercialization rights for #Apealea to #InceptuaGroup https://t.co/ANPVuPnq2v" (@1stOncology)

All-trans retinoic acid in anticancer therapy: how nanotechnology can enhance its efficacy and resolve its drawbacks. (PubMed, Expert Opin Drug Deliv) - "Pre-clinical results obtained with nanoencapsulated ATRA are shown as well as the two ATRA products based on nanotechnology that were clinically tested: ATRA-IV® and Apealea®...Bioavailability and resistance limitations impair the use of ATRA in non-APL cancers. Nanotechnology can circumvent these issues and provide tools to enhance its anticancer activities, such as co-loading of multiple drug and active targeting to tumor site."

Clinical • Journal • Acute Promyelocytic Leukemia • Hematological Malignancies • Leukemia • Oncology

Elevar Therapeutics Announces Licensing Agreement with Inceptua Group for Commercialization of Apealea (Paclitaxel Micellar) in Europe (PRNewswire) - "Elevar Therapeutics...today announced that it has entered into an exclusive agreement with Inceptua Group ('Inceptua') for the distribution and commercialization of Apealea® (paclitaxel micellar) in Europe. Apealea has been authorized by European regulatory authorities for use in the European Economic Area in combination with carboplatin for the treatment of adult patients with first relapse of platinum-sensitive epithelial ovarian cancer, primary peritoneal cancer and fallopian tube cancer."

Licensing / partnership • Fallopian Tube Cancer • Gynecologic Cancers • Oncology • Ovarian Cancer

Comparing 2D and 3D culture models for in vitro therapeutic screening of paclitaxel loaded micelles co-administered with iRGD peptide (AACR 2018) - "The cytotoxicity of the micellar paclitaxel nanocarrier system was studied in both the 2D and 3D cell culture models. Significantly higher concentration of the drug was needed in the 3D cultures to achieve comparable levels of cytotoxicity to the 2D cell culture models. This suggested that multicellular tumor spheroids exhibit higher resistance to anticancer drugs, supporting the fact that 3D culture is the better model to study in vitro cytotoxicity and likely to produce biorelevant data."

Triple Negative Breast Cancer

Elevar Therapeutics and Taiba Middle East FZ LLC Partner to Commercialize Apealea (paclitaxel micellar) in the Middle East and North Africa Region (PRNewswire) - "Elevar Therapeutics...has entered into an exclusive agreement with taiba Middle East FZ LLC ('taiba') under which taiba will commercialize and distribute Apealea® (paclitaxel micellar) in certain countries throughout the Middle East and North African (MENA) region. Apealea has been approved by the European regulatory authorities for use in combination with carboplatin for the treatment of adult patients with first relapse of platinum-sensitive epithelial ovarian cancer, primary peritoneal cancer and fallopian tube cancer."

Licensing / partnership • Gynecologic Cancers • Oncology • Ovarian Cancer

Elevar Therapeutics and Tanner Pharma Group Announce Launch of Global Named Patient Program to Provide Access to Apealea (paclitaxel micellar) (PRNewswire) - "Elevar Therapeutics, Inc...and Tanner Pharma Group...announced today that they have launched a global named patient program to facilitate access to Apealea® (paclitaxel micellar) on a named patient basis in areas outside of the United States (U.S.) and Middle East North Africa (MENA) where Apealea is not yet commercially available. Apealea has been approved by the European regulatory authorities for use in combination with carboplatin for the treatment of adult patients with first relapse of platinum-sensitive epithelial ovarian cancer, primary peritoneal cancer and fallopian tube cancer."

Clinical • Fallopian Tube Cancer • Gynecologic Cancers • Oncology • Ovarian Cancer • Peritoneal Cancer

"#Oasmias Partner #Elevar Provides an Update on #Apealea Development Plans in #OvarianCancer https://t.co/4PqsQ1AXCw" (@1stOncology)

Gynecologic Cancers • Oncology • Ovarian Cancer • Solid Tumor

Drug-coated balloons show benefits for patients with dysfunctional dialysis fistulas (Healio) - '"Standard percutaneous transluminal angioplasty is the current recommended treatment for dysfunctional hemodialysis fistulas, yet long-term outcomes of this treatment are poor,' Robert A. Lookstein, MD, of Icahn School of Medicine at Mount Sinai, and colleagues wrote. 'Drug-coated balloons delivering the antirestenotic agent paclitaxel may improve outcomes'....'In defining the benefits of this therapy, it is notable that dialysis circuit stenoses have indirect consequences that go far beyond local hemodynamic effects,' Lookstein and colleagues added. 'If a patient has a dysfunctional arteriovenous fistula, placement of a central venous catheter is often used as an alternative form of dialysis.'"

Media quote

Elevar Therapeutics and Tanner Pharma Group Announce Global Named Patient Program to Provide Access to Apealea (micellular paclitaxel) (PRNewswire) - "Elevar Therapeutics, Inc...and Tanner Pharma Group...today announced a partnership that will facilitate access to Apealea® (micellular paclitaxel) on a named patient basis in areas outside of the United States (U.S.) where Apealea is not commercially available...Under the terms of the agreement, Tanner will be the exclusive supplier of Apealea to health care providers outside of the U.S. on a named patient basis in countries where Apealea is not yet commercially available."

Licensing / partnership • Oncology

Pharmacokinetics of Total and Unbound Paclitaxel After Administration of Paclitaxel Micellar or Nab-Paclitaxel: An Open, Randomized, Cross-Over, Explorative Study in Breast Cancer Patients. (PubMed, Adv Ther) - "The two formulations, paclitaxel micellar and nab-paclitaxel, behaved similarly following infusion. Probably, both formulations dissociate immediately in the blood, whereupon released paclitaxel rapidly distributes into tissue. Judged from the bioequivalence demonstrated for unbound paclitaxel, the two formulations are considered clinically equivalent."

Clinical • Journal • PK/PD data • Breast Cancer • Oncology • Ophthalmology • Solid Tumor

Interim report for the period May 2013 - January 2014 (Oasmia Press Release) - "Oasmia has performed a phase III study with paclical...the final patient was treated in the beginning of 2013. All patients have been followed up regarding time to progression. Oosmia is now evaluating the results, which will be used for submission of marketing authorization applications for Paclical in the EU, US and the rest of the world."

Anticipated EU regulatory • Anticipated NDA • Ovarian Cancer

In Vitro Effects of the Chemotherapy Agent Water Soluble Micellar Paclitaxel (Paccal Vet) on Canine Hemangiosarcoma Cell Lines. (PubMed, Vet Comp Oncol) - "Reverse transcriptase-PCR was performed on the cell lines to validate the gene expression of VEGF and bFGF. Results obtained from this study support future studies involving the use of paclitaxel (micellar) for treatment of canine hemangiosarcoma. "

Journal • Preclinical • Biosimilar • Oncology • Sarcoma • Solid Tumor

Maximum Tolerated Dose and Pharmacokinetics of Paclitaxel Micellar in Patients with Recurrent Malignant Solid Tumours: A Dose-Escalation Study. (PubMed, Adv Ther) - "No new side effects unknown for paclitaxel were observed. Maximum plasma concentration (C) and AUC showed a tendency to increase linearly with dose within the 150-275 mg/m dose range. The possibility to administer paclitaxel micellar without steroid premedication makes it an attractive candidate for further studies in combination with immunotherapy."

Clinical • Journal • PK/PD data

"Elevar Therapeutics Acquires Worldwide Development and Commercialization Rights for Oasmia’s Apealea @Oasmia https://t.co/2QkW2T9cfC" (@Pharmashot)

Elevar Therapeutics acquires global rights to European approved Apealea from Oasmia Pharmaceutical (PRNewswire) - "Elevar Therapeutics, Inc...announced...an agreement with Swedish-based Oasmia Pharmaceutical AP to obtain global rights for Apealea®, except in Nordics, Russia, and certain countries in Eastern Europe....The companies are also in discussions with the FDA to determine the best route for a New Drug Application (NDA) in the US."

Licensing / partnership • NDA

Different nanoformulations alter the tissue distribution of paclitaxel, which aligns with reported distinct efficacy and safety profiles. (PubMed, Mol Pharm) - "...All nanoformulations were associated with paclitaxel blood-cell accumulation in mice; however, m- nab-paclitaxel was associated with the lowest accumulation...The solvent-based formulation was associated with the poorest paclitaxel penetration in all tissues and the lowest tissue-to-plasma ratio. The different nanocarriers of paclitaxel were associated with distinct pharmacokinetics and tissue distribution, which largely align with the observed efficacy and toxicity profiles in clinical trials."

Clinical • Journal

Oasmia Pharmaceutical AB receives positive opinion from the European Medicines Agency to add efficacy data to the approved Apealea product information (GlobeNewswire) - "Oasmia Pharmaceutical AB...announce that the European Medicines Agency (EMA) has adopted a positive opinion recommending approval of a type II variation application to add efficacy data to the Apealea product information....The marketing authorisation approval for Apealea in the EEA was based on the phase III pivotal study OAS‑07OVA. The study was conducted on 789 randomized patients with relapse of ovarian cancer disease that were treated with paclitaxel in combination with carboplatin."

European regulatory

European Medicines Agency validates Oasmia Pharmaceutical AB’s application to add efficacy data to the approved Apealea product information (Oasmia Press Release) - "Oasmia Pharmaceutical AB...announce that the European Medicines Agency (EMA) has validated a type II variation application to add efficacy data to the Apealea product information...Oasmia anticipates an opinion from the Committee for Medicinal Products for Human Use (CHMP) by end of Q1 or beginning of Q2 2019....The application is based on subpopulation data (n=599) from the OAS-07OVA study and aims to provide treating physicians with efficacy data for Apealea in combination with carboplatin for the approved indication; adult patients with first relapse of platinum-sensitive epithelial ovarian cancer, primary peritoneal cancer and fallopian tube cancer."

European regulatory