Orphan oncology products

LIVATAG®

livatag-EN

Primary liver cancer

Hepatocellular carcinoma (primary liver cancer) is the sixth most common cancer in terms of incidence (782,000 new cases per year) and the second leading cause of cancer deaths worldwide. It occurs in 80-90% of cases in patients with liver cirrhosis mainly due to viruses (virus B and C), alcohol or metabolic syndrome. It is a highly chemotherapy-resistant cancer, often diagnosed at an advanced stage and for which there is a very strong unmet therapeutic need today.

The product

 Livatag® is a nanoparticle formulation of doxorubicin (Transdrug™ technology) developed for the treatment of primary liver cancer.

Transdrug™ technology uses nanoparticles to help fight against chemotherapy resistance, a major mechanism in the failure of some anticancer drugs, that facilitate the penetration of the drug into the tumor cell and increase the cellular exposure to the drug.

Livatag® uses this technology along with doxorubicin in the treatment of advanced primary liver cancer. It allows bypassing the mechanisms of multi-drug resistance developed by tumour cells. Encapsulated in the form of nanoparticles, doxorubicin can then reach  its  therapeutic target and exert its cytotoxic activity.

The Phase II clinical trial has shown that intra-arterial administration of Livatag® increased survival time of patients suffering from hepatocellular carcinoma by 17 months, as compared to 15 months for patients getting current best of care (TACE transarterial chemoembolisation with a cytotoxic drug).

Based on this data, an international, open randomised Phase III clinical trial (ReLive) comparing repeated intravenous administration of Livatag® to the best standard of care has been implemented in 400 patients with advanced-stage hepatocellular carcinoma, after failure or intolerance to Sorafenib. A committee of independent experts regularly reviews the tolerance of the treatment administered.

Livatag®, key program of the Orphan Oncology Products and core of Onxeo’s  growth strategy, has obtained orphan drug status in two major territories, Europe and the USA, thus enhancing the value of this key asset for the Company.

Livatag® has also obtained Fast Track status (accelerated review procedure)  from the FDA for the treatment of hepatocellular carcinoma (primary liver cancer) after treatment with Sorafenib (Nexavar®). This status recognizes that a drug is being developed for a severe or life-threatening pathology with a significant medical need. It will allow enhanced interaction with the FDA and optimize the evaluation schedule of the product during development and right up to registration.

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BELEODAQ®

beleodaq-EN

Peripheral T-Cell Lymphoma (PTCL)

Lymphoma is the most common blood cancer*. Hodgkin’s and non-Hodgkin’s lymphoma are the main two forms of lymphoma. The lymphoma survives when the lymphocytes, a type of white blood cell, increase abnormally and accumulate in one or more lymphatic ganglions or in lymphatic tissue. Two types of lymphocytes may develop: B lymphocytes (B cells) and T lymphocytes (T cells). Peripheral T-Cell Lymphoma (PTCL) is a sub-type of non-Hodgkin’s lymphoma which affects T cells. In the United States, PTCL accounts for around 10 to 15% of non-Hodgkin’s lymphoma and its global incidence is estimated at 12,000 cases each year. Currently no 2nd line treatment is available in Europe once the disease has progressed after a 1st line of treatment.
*Lymphoma Research Foundation (www.lymphoma.org)

The product

Belinostat is a histone deactylase inhibitor (HDACi). It has been assessed in several clinical trials as a sole treatment (monotherapy) or in combination with other anti-cancer treatments for hematological cancers and solid tumors. Its anti-cancer activity is associated with the inhibition of cell proliferation, the induction of apoptosis (programmed cell death), the inhibition of angiogenesis and the induction of cellular differentiation.

The company also plans to instigate in the coming months a development program on one or more potential indications based on the clinical results already obtained.

Since 2010, Beleodaq® has been licensed to an American partner, Spectrum Pharmaceuticals, Inc. (SPPI), for the USA and India. Spectrum Pharmaceuticals is responsible for the co-development of Beleodaq® for the United States and for promoting it to oncology and hematology specialists.

Beleodaq® benefits from industrial protection until at least 2026. Its protection (commercial exclusivity) is furthermore strengthened by its status as an orphan drug in Europe and the United States.

Developed to tackle relapsed or refractory peripheral T-cell lymphoma (PTCL), with a positive Phase II, in early July 2014 Beleodaq® obtained New Drug Authorization from the Food and Drug Administration for this indication. This authorization was given within the context of an accelerated registration program which conditionally approves a drug designed for the treatment of a life-threatening disease based on predictive elements of a clinical benefit. The registration is based on the results of the BELIEF clinical trial of 129 patients suffering from peripheral T-cell lymphoma, resistant or in relapse after at least one initial systemic treatment which showed a response level of 25% with a median duration of response of 8.3 months and a good tolerance profile.
Beleodaq® has been available to patients since July 2014, promoted by specialist Spectrum Pharmaceuticals oncology sales teams in the United States.

A clinical Phase III trial is planned to assess the efficacy of Beleodaq® in combination with the CHOP treatment, against CHOP in the 1st line of treatment of peripheral T-cell lymphoma (PTCL).

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AsiDNA™

AsiDNA-EN

The product

First-in-class signal-interfering (siDNA) product candidate, AsiDNA™ breaks the cycle of tumor DNA repair by interfering at the core of DNA damage, blocking multiple repair pathways, while sparing healthy cells. AsiDNA™ and its technology originate from three major French academic centers: Curie Institute, CNRS, and the Museum of Natural History. It offers a potential new treatment option for patients suffering from various types of cancer.

ENG lille

DNA damages of cancer cells are caused by cytotoxics (chemo- and radiotherapies) or occur spontaneously in the case of certain genetically unstable tumors. Cancer cells have the ability to recognize DNA damage and activate multiple repair pathways or proteins to survive DNA damages. Approaches to prevent DNA repair mechanisms have been identified as one of the most promising new avenues in cancer treatment.

AsiDNA™ is a short double-stranded DNA molecule that acts as a decoy, mimicking double-strand breaks in the cell’s native DNA. When introduced into a cell, AsiDNA™ molecules trigger false DNA break signals to activate and attract DNA repair proteins, which prevents the recruitment of repair enzymes to the site of actual DNA damage. As a result, the damage of a cell’s native DNA remains unrepaired. As cancer cells have lost the ability to regulate cell division, they will continue dividing with damaged DNA, ultimately leading to cancer cell death (mitotic death). Healthy cells, on the other hand, will halt cell division until the compound is no longer present and damaged DNA can be repaired.

This approach is significantly differentiated from others in the field as it does not inhibit specific enzymes (such as the PARP-inhibitors) but targets the entire DNA repair system.

asidna-eng

A first-in-human Phase I trial performed in metastatic melanoma demonstrated that the siDNA molecules showed good tolerance and safety when administered intra-tumorally and subcutaneously around the tumors.

Onxeo plans to initate the development of the product by the systemic route, and to assess safety and tolerance in monotherapy and in combination with other DNA-damaging agents in various solid tumors. This clinical development will be implemented after first optimizing the manufacturing process.

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VALIDIVE®

Validive-EN

Oral mucositis

Oral mucositis is an inflammation of the oral mucosa occurring in 80-100% of patients treated with radiotherapy/chemotherapy for head and neck cancer. Its impact and severity are proportional to the intensity of the irradiation. Severe oral mucositis (grade 3 and 4 of the WHO classification) causes intense pain, odynophagia (difficulty swallowing) and/or dysphagia leading to difficulty eating and may require parenteral or enteral feeding. In 30% of cases, the impaired general condition caused by oral mucositis leads to the patient’s hospitalisation and sometimes discontinuing for long periods the cancer treatment protocol, which may reduce the treatment’s efficacy. To date, no effective prevention or treatment of oral mucositis induced by radiotherapy/chemotherapy is available.

The product

Validive® is a mucoadhesive buccal tablet containing clonidine (Lauriad® technology) developed for the prevention and the treatment of chemoradioation therapy-induced severe oral mucositis in patients with head and neck cancer.

Validive® is an agonist of the alpha-2 adrenergic receptors. Stimulation of these receptors decreases the expression and release of pro-inflammatory cytokines from the macrophages and leukocytes of the oral cavity, which is one of the initiating mechanisms triggering oral mucositis. The Lauriad® technology, owned by Onxeo, significantly increases the mucous and salivary concentrations of the active ingredient it contains, with decreased systemic absorption.

Experimental studies on human gum and in hamsters having one of their jowls irradiated, confirmed the action mechanism of Validive®. They also showed that Validive® reduced the incidence and severity of experimental oral mucositis.

An international multicentre randomised double-blinded Phase II clinical trial comparing the efficacy and safety of two doses of Validive® (clonidine Lauriad®) to those of  placebo in the prevention and the treatment of oral mucositis induced by radiotherapy and chemotherapy was conducted in Europe and in the US in 183 patients with head and neck cancer and having undergone resectible surgery. The final data from this global Phase II clinical trial of Validive® (presented during a poster session at the 2015 ASCO meeting) confirmed the therapy’s favorable safety profile and efficacy in reducing severe oral mucositis in patients with head and neck cancer receiving chemoradiation therapy. The company is seeking for a partner to further co-develop Validive®.

Validive® was granted orphan drug status in Europe, which enhances the value of the second drug of the Orphan Oncology Products portfolio.

Validive® also received Fast-Track status in January 2014 from the Food and Drug Administration (FDA) in the prevention and treatment of oral mucositis induced by radiotherapy and/or chemotherapy for patients being treated for cancer. This status shows Agency recognition of oral mucositis severity and medical needs that Validive® could address. It will allow enhanced interaction with the FDA and optimize the evaluation schedule of the product during development and right up to registration.

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