In July 2017, the Company announced the sale of two historical products Sitavig® and Loramyc® to Vectans Pharma, a private pharmaceutical company which develops and markets innovative therapeutics in oral pathologies. Under this agreement, Onxeo assigns to Vectans Pharma all assets relating to the two products – notably patents, regulatory authorizations and outstanding contracts – and receives an upfront payment of €4 million, as well as a potential earn-out payment based on the cumulated worldwide commercial performance of the products. In addition, Onxeo will receive most of the expected milestone payments from existing partners, related to predefined regulatory or commercial performance events expected over the next 3 years.
In September 2017, Onxeo announced that it has granted a global exclusive license of Validive® (clonidine mucoadhesive buccal tablet) developed for the treatment of severe oral mucositis induced by radiotherapy or chemotherapy in patients suffering from head and neck cancer to Monopar Therapeutics (Chicago, Illinois, USA), a biopharmaceutical company focused on developing innovative drug combinations to improve clinical outcomes in advanced cancer. The agreement includes substantial milestone payments up to $108m as well as escalating royalties on future sales. Monopar Therapeutics will drive and fund all remaining development, regulatory and commercialization activities.
Please refer to the relevant press release for more information on these transactions.
 Loramyc® is also known as Oravig® in the US and China, and Oravi® in Japan – Sitavig® is also known as Labiriad® in Italy.
Oropharyngeal candidiasis is a fungal infection of the oropharynx induced by yeast-like fungi: Candida albicans and non-albicans. This is an opportunistic disease that develops due to a failure of the immune system and/or a local imbalance. Some treatments favour the development of fungal infections such as immunosuppressive therapy, radiation therapy, chemotherapy, long-term antibiotics, and systemic or inhaled corticosteroids taken over long periods. This disease affects the quality of life of patients suffering and struggling to feed themselves.
Loramyc®/Oravig® is a mucoadhesive buccal tablet (Lauriad® technology) containing miconazole. Pharmacokinetic studies in man have shown that Loramyc® (in Europe)/Oravig® (in the US) delivers early and continuous high salivary concentrations of miconazole. Randomized Phase III clinical trials have confirmed the efficacy of Loramyc®/Oravig® in the treatment of oropharyngeal candidiasis in patients with head and neck cancer or AIDS.
Loramyc®/Oravig® is the first product developed by Onxeo and approved in Europe and the USA. Loramyc® is marketed through partnership agreements in Europe with the Therabel Group, in the US with Dara BioSciences, in Southeast Asia with Handok, in China with SciClone Pharmaceuticals, and in Japan with Sosei.View press releases
Herpes labialis (often called “cold sores”) is an infection that occurs in outbreaks, recurring more or less frequently. It usually appears as vesicular lesions progressing toward ulceration and then turns into a scab located on the lips, accompanied by burning and itching. Herpes labialis is caused by the herpes simplex virus. Herpes labialis is a benign condition but recurrent and contagious.
Herpes labialis is an extremely widespread infection that affects nearly 100 million people in the world each year. It has an estimated annual prevalence at 15% of the adult population or about 40 million people in the United States and more than 100 million episodes of herpes labialis per year. The potential market for Sitavig® can be estimated at several hundred million dollars.
Sitavig® (Europe, USA)/Labiriad® (Italy) is a mucoadhesive buccal tablet (Lauriad® technology) containing acyclovir. Pharmacokinetic studies in healthy volunteers showed that Sitavig® quickly delivers very high concentrations of acyclovir into the saliva for about 24 hours but also onto the lips, the site of infection. An international randomised phase III clinical trial in 775 immunocompetent patients with recurrent herpes labialis showed the efficacy and good tolerance of Sitavig® . This drug also reduces the duration of the herpes episode. Sitavig® is approved in the United States and in nine European countries (France, Germany, Sweden, the United Kingdom, Spain, Italy, Denmark, Finland, and Norway).
In March 2014, a licensing agreement was entered into with Innocutis Holding LLC for the marketing of Sitavig® in the U.S. which launched the product on the U.S. market in July 2014. In April 2015, the licensee Innocutis was acquired by Cipher Pharmaceuticals which pursues the partnership with Onxeo.
Other licensing agreements were signed: with Teva group in Israel, Daewoong Pharmaceutical Co.Ltd in South Korea and EMS S/A in Brazil, including the responsability for registering the product with each country’s regulatory authorities.
More recently, in July 2015, Onxeo signed a license agreement for Sitavig® with specialty pharmaceutical company Bruno Farmaceutici for commercialization in Italy. As a partner, Bruno Farmaceutici will launch Labiriad® (name of Sitavig® in Italy) under its current regulatory status (prescription) and manage the regulatory procedure to obtain an over-the-counter (OTC) designation, allowing pharmacists to deliver Sitavig® to patients directly.
View press releases
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.
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.
Validive® was granted orphan drug status in Europe.
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.
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 has stated in 2016 that it was looking for a partner to develop Validive® further. In September 2017, Onxeo announced that it has granted a global exclusive license of Validive® (clonidine mucoadhesive buccal tablet) developed for the treatment of severe oral mucositis induced by radiotherapy or chemotherapy in patients suffering from head and neck cancer to Monopar Therapeutics (Chicago, Illinois, USA), a biopharmaceutical company focused on developing innovative drug combinations to improve clinical outcomes in advanced cancer. The agreement includes substantial milestone payments up to $108m as well as escalating royalties on future sales. Monopar Therapeutics will drive and fund all remaining development, regulatory and commercialization activities.
Please refer to the press release for more détails on this transaction.View press releases
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.
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.
Livatag® 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.
The Phase II clinical trial showed that intra-arterial administration of Livatag® in patients suffering from hepatocellular carcinoma provided a median survival of 32 months, an increase of 17 months when 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 randomized 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 has regularly reviewed the tolerance of the treatment administered.
The company announced on September 11, 2017 that ReLive did not meet its primary endpoint of improving survival over the comparative group. The major reason is an unexpected high survival in the comparative group. Indeed, the study was not placebo controlled and patients in the comparative group could receive other anticancer agents (including oxaliplatin, gemcitabine or tyrosine kinase inhibitors) which might explain the high survival rate of the control arm. Livatag®, as single agent, showed a similar effect as the one observed in that comparative group with active treatments. There was no difference in efficacy between the two arms (Livatag® 20mg/m² and 30mg/m²). The overall safety and tolerability profile of Livatag® in ReLive was favorable with a fully manageable toxicity profile in both groups of Livatag (20mg/m² and 30mg/m²) including in those patients who underwent the longest treatment periods, over one year. The overall tolerability was comparable to the one observed in the comparative group. The main results from the ReLive study were presented at the 11th Annual Conference of the International Liver Cancer Association in Seoul, South Korea (ILCA 2017 – September 15-17, 2017).
The study protocol can be downloaded here.
Pleaser refer to the press release and data presentation for additional information.