AE 941 [Arthrovas™, Neoretna™, Psovascar™] is shark cartilage extract that inhibits angiogenesis. AE 941 acts by blocking the two main pathways that contribute to the process of angiogenesis, matrix metalloproteases and the vascular endothelial growth factor signalling pathway.When initial development of AE 941 was being conducted, AEterna assigned the various indications different trademarks. Neovastat™ was used for oncology, Psovascar™ was used for dermatology, Neoretna™ was used for ophthalmology and Arthrovas™ was used for rheumatology. However, it is unclear if these trademarks will be used in the future and AEterna appears to only be using the Neovastat™ trademark in its current publications regardless of the indication.AEterna Laboratories signed commercialisation agreements with Grupo Ferrer Internacional SA of Spain and Medac GmbH of Germany in February 2001. Under the terms of the agreement, AEterna has granted exclusive commercialisation and distribution rights to AE 941 in oncology to Grupo Ferrer Internacional for the Southern European countries of France, Belgium, Spain, Greece, Portugal and Italy. It also has rights in Central and South America. Medac GmbH will have marketing rights in Germany, the UK, Scandinavia, Switzerland, Austria, Ireland, the Netherlands and Eastern Europe.In October 2002, AEterna Laboratories announced that it had signed an agreement with Australian healthcare products and services company Mayne Group for marketing AE 941 (as Neovastat™) in Australia, New Zealand, Canada and Mexico.In March 2003, AEterna Laboratories announced it has signed an agreement with Korean based LG Life Sciences Ltd for marketing AE 941 (as Neovastat™) in South Korea. The agreement provides AEterna with upfront and milestone payments, as well as a return on manufacturing and sales of AE 941.[1]AEterna Laboratories had granted Alcon Laboratories an exclusive worldwide licence for AE 941 for ophthalmic products. However, this licence has been terminated.In 1999, AEterna secured funding for AE 941, part of which is from Technology Partnerships Canada (TPC), a research support programme run by Canada's federal government. Industry Canada will contribute $Can1 for every $Can3 spent by AEterna on the development of AE 941, up to a total figure of $Can29.4 million. AEterna will reimburse TPC upon commercialisation of AE 941-derived products as a royalty on income generated.In January 2004 AEterna announced that development of AE 941 would be focusing on non-small cell lung cancer and that development for renal cell carcinoma would be discontinued.[2]AEterna had previously announced in January 2003, following its acquisition of Zentaris, that development of AE 941 would be "strictly focused" on renal and non-small cell lung cancer, suggesting that development for all other indications has been discontinued, at least for the foreseeable future.In May 2002, in its Annual Information Form, AEterna announced that resources or collaborations would be required before further development of indications other than cancer could take place. The company also announced the discontinuation of development in the area of arthritis at that time.Initiated in May 2000, this phase III trial is being led by researchers from the MD Anderson Cancer Center in Houston, Texas, USA. In addition, enrolment at approximately 70 other sites in the US and Canada was scheduled to begin in 2001. This randomised, controlled study will evaluate the efficacy of AE 941 as adjunctive treatment to standard chemotherapy and radiotherapy. The study is expected to enrol 760 patients, with trial completion targeted for 2005. The Radiation Therapy Oncology Group (RTOG) has joined the Community Clinical Oncology Programme (CCOP) in recruiting patients and in the execution of the phase III trial in NSCLC. The commitment of these two groups in the trial will complement the support provided by the MD Anderson Cancer Center and the NCI.AEterna signed a Clinical Trials Agreement (CTA) with the NCI for the realisation of another pivotal phase III clinical trial of AE 941 for the treatment of NSCLC in combination with chemo- and/or radiotherapy. The trial was initiated in early 1999 and will enrol up to 550 patients in the US and Canada.Phase I/II Canadian and US trials of AE 941 have been completed for the treatment of refractory lung cancer (n = 80).Previously, AEterna had reported results of an open-label, phase I/II study in patients with NSCLC at the 10th European Cancer Conference in Vienna (ECCO-1999) in September 1999. The results were published in early 2003 inClinical Lung Cancer.In October 2003, AEterna reported that AE 941 did not meet its primary endpoint of improving survival time in its phase III trial of AE 941 in patients with renal cell carcinoma. However, significant survival advantage was observed in a subgroup of healthier patients with clear cell histology and only a single metastatic site. This 38-patient subgroup showed a median survival time of 26.3 months for those treated with AE 941 compared with 12.6 months for patients receiving a placebo. In June 2003, AEterna reported that the number of deceased patients was 218.[3]Enrolment of patients into this pivotal phase III was completed in December 2001 at approximately 50 sites in the US, Canada, Belgium, France, Germany, the UK, Czech Republic, Poland and Argentina. AEterna has completed a planned safety analysis of the renal cancer trial (conducted by the Data Safety Monitoring Board), with positive results reported. AEterna announced in June 2002 that it expected the study to be completed in <12 months.The US FDA granted orphan drug status to AE 941 for the treatment of renal cell carcinoma in October 2002. AEterna had hoped to launch the drug for renal cancer in 2004.AEterna has been issued with four key patents (nos. 6 168 807, 5 618 925, 5 985 839 and 6 025 334) from the US Patent and Trademark Office, protecting AE 941, the process by which it is manufactured and the medical uses of the product in several therapeutic areas.AEterna has isolated a series of potent anti-angiogenic molecules from AE 941 and has filed a patent application with the US Patent and Trademark Office related to this finding.In a report published by BLC Securities (Laurentian Bank) on AEterna Laboratories (9 March 2000) it was stated that the US market launch of Neo-vastat™, as a second-line therapy for renal cell cancer, is expected to occur in the second quarter of 2002, while launch as an adjunctive therapy for non-small cell lung cancer is expected to happen in the first quarter of 2004. Sales in Europe are forecast to begin 1 year after the US launch, with a launch in the rest of the world 2 years after the initial launch.The worldwide market for adjuvant/supportive care therapies is expected to reach $US5.1 billion in 2002, and is an important market for AEterna, according to BLC Securities, since Neovastat™ is being developed as an adjunctive therapy to standard non-small cell lung cancer therapy. BLC Securities expects AEterna to sign a licensing agreement for Neovastat™ during 2000 for the marketing and distribution of the product in North America. If a strategic partner is found, it could bring AEterna $US35 million in licensing fees and milestone payments. In the report, royalty rates on worldwide sales are set at 15% (oncology) and 8% (dermatology).AEterna reported a net loss of $US1.9 million during the first quarter of 1999, which it attributed to the cost of setting up the phase III trial for the treatment of non-small cell lung cancer in combination with chemo- and/or radiotherapy.In the same report published by BLC Securities (Laurentian Bank) on AEterna Laboratories on 9 March 2000, it was stated that the US market launch of AE 941 – Psovascar is expected to occur in the fourth quarter of 2004, followed by a launch in Europe and the rest of the world 1 and 2 years, respectively, after the initial launch. BLC Securities is forecasting a maximum market penetration for the product of 4%, based on a highly competitive psoriasis market. The report also stated that the annual therapy price had been set to $US2500, reflecting the facts that AE 941 – Psovascar is seen as an adjunct to existing therapies and “given the likelihood that the treatment will be a rotating therapy”. More than 6.4 million people are estimated to suffer from psoriasis in the US, according to the report quoting the US National Psoriasis Foundation (NPF), with more than 200 000 new cases every year; over 100 million people are affected by the disease worldwide.In addition, the report published by BLC Securities (Laurentian Bank) on AEterna Laboratories on 9 March 2000 stated that the wet age-related macular degeneration (AMD) market is estimated to be worth $US1.5 billion, based on patients paying $US9000–$US12 000 per year on a lifetime basis. The report states that 1.7 million Americans >65 years of age were estimated to have AMD in 1997, with 200 000 new cases being diagnosed every year. For this forecast, BLC Securities is quoting sources such as QLT Phototherapeutics, Miravant, The US National Eye Institute, NIH and The American Macular Degeneration Foundation. QLT Phototherapeutics and Miravant expects AMD phototherapy to cost $US3000 per treatment, with at least three or four treatments necessary to maintain the results of treatment with Visudyne™.