#	Pagina
attuale pagina	/open-h2020/projects/223078/results.html
-1	/open-h2020/projects/215542/index.html

Report

Teaser, summary, work performed and final results

Periodic Reporting for period 1 - Hyalcis (Hyaluronic-Cisplatin Film for Implant in Malignant Mesothelioma Recurrence)

Teaser

Summary

Mesothelioma is a rare malignancy attacking the mesothelia, i.e. the cells lining pleural and peritoneal cavities and pericardium. This neoplasia appears long time after inhalation of the asbestos fibres. The most cases of malignant mesothelioma are pleural in origin (malignant pleural mesothelioma, MPM). MPM is a very aggressive form of cancer and the patients have a very low expectancy of life.
This is a dramatic medical/social problem to solve. Nowadays, MPM therapy combines a demanding systemic chemotherapy, followed by surgery and post-operative radiotherapy to the resected area. In various surgical centres, following the resection of the primary tumour, the surgeons wet the area involved in tumour growth with a solution of cytostatic drug, such as cisplatin. This action is called intracavitary treatment. However, these treatments do not completely cure, since frequent local recurrences or metastasis appear in the surgery resected area. Consequently, for these patients, after surgery, the overall median survival is between 16.8 and 23 months, due to metastases appearance.
Why is it important for society?
A novel product in form of biodegradable solid film for intracavitary or loco-regional cytostatic treatment, to be stuck on the mesothelium area from where the primary tumour was removed, has been invented. The film optimizes the existing intracavitary therapy. The new product more effectively tackles the metastasis occurrence by increasing the precision and accuracy of the medication. PlumeStars invented this medicinal product, making a prototype named Hyalcis. The company wants to make it available for surgeons and patients.
There are three main reasons for investing for the market authorization of Hyalcis, the cisplatin/hyaluronate film:
1) economic: the orphan designation obtained from EMA and FDA gives a unique position and global market recognition for the company registering the product; moreover; the advantages for the company are the low costs of development and the product value in hospital use.
2) medical: meeting the expectation of patients and satisfying the endorsement of surgery doctors, to which the film provides a novel therapeutic instrument for contrasting the local MPM metastasis appearance; this increases the life quality and survival expectation of patients.
3) societal: mesothelioma tumours incidence will peak in EU and extra-community countries in the next years.
The key objective of the terminated Phase I SME instrument was the preparation of a detailed Business Plan within 6 months, in order to support the search for funding in view of product marketing authorization request to EMA and FDA.

Work performed

Hyalcis is a biodegradable film of hyaluronic acid (HA) loaded with the anticancer drug cisplatin, to be stuck on the mesothelial tissues during surgery for primary tumour resection. Cisplatin, approved since 1978 for the treatment of malignant mesothelioma, by intravenous administration is extremely toxic. The solution invented by PlumeStars consisted in the local application on pleura of thin and flexible HA biodegradable film loaded with cisplatin, to adhere to mesothelial surfaces. The cisplatin released from film provides high and prolonged local drug concentrations, directly on the site where residual tumour could reappear. The high local cisplatin concentration could not be obtained by intravenous administration, unless exposing the patient to unacceptable risks of toxicity. The expected effect is a long-lasting prevention of local tumour recurrences and increase of life expectation.
The main results achieved in this Feasibility Study project include:
- Product pre-clinical and clinical studies detailed planning.
- Market analysis and commercialization planning.
- Industrialization planning.
- Legal-ethical framework and intellectual property strategy definition.
- Economic feasibility assessment.

Final results

Hyalcis film, tested on animal models (rat and sheep) revealed significant benefits that were recognized by the EMA when the orphan designation was given:
1) Effectiveness. The cisplatin/hyaluronate film applied on the animal chest had two advantages: i) due to the local cavity absorption, the drug exposure of pleura mesothelium greatly increased, ii) drug clearance was slowed down.
2) Low toxicity. A preclinical pharmacokinetic and toxicity study has been carried out on sheep. Also the loco-regional drug administration of cisplatin solution reduced the toxic effects in MPM patients, compared to i.v. chemotherapy but the effectiveness was low.
3) Safer and very efficient drug administration. The sheep study has been aimed also to test in large animals the pleural application of cisplatin/hyaluronate film, in order to assess the film handle ability in surgical practice, drug release and bioavailability. The film application had no critical risks for surgery personnel, unlike the intrapleural cisplatin solution that could leak from the cavity, due to the pressure applied during surgical suture.

On 29 August 2016, the Orphan Medicinal Product designation (EU/3/16/1719) was granted by the European Commission to PlumeStars, for the cisplatin/hyaluronate film, named Hyalcis, for local treatment of MPM. Hyalcis is an intracavitary film to stuck, during tumour surgery, on lung pleura to prevent local MPM metastases. The designation of orphan medicine has also been obtained by US FDA.
The orphan designation entitles PlumeStars as unique owner of Hyalcis product. Thus, it is a company value and offers business perspectives that PlumeStars intends to exploit. In details, no similar product for the local treatment of mesothelioma recurrences exists on the market. Starting from the registration date, Hyalcis marketing authorization will give to PlumeStars 10 years of market exclusivity in Europe (7 years in USA). More than 43,000 people die each year worldwide for mesothelioma and 10,000 new cases in Europe, North America, occur each year. The value of mesothelioma market is estimated at over 600 M Euro. PlumeStars intends to reach 28% of this market within 8 years from the end of the SME Phase 2 project (see Section 2). The market dimension could expand beyond mesothelioma treatment, since this medicine can be proposed for other sensitive cancers surgically treated, such as the ovarian or peritoneum cancers. Thus, an inviting opportunity for creating new jobs for the manufacturing line of new film products and larger market is present.