Calcitonin intranasal--unigene: Salcatonin intranasal--unigene.

Abstract

An intranasal spray formulation of recombinant salmon calcitonin [salcatonin] is in development with Unigene Laboratories as therapy for postmenopausal osteoporosis. Calcitonin is an endogenous polypeptide hormone that regulates calcium and bone metabolism. It is produced by the parafollicular cells of the thyroid gland in humans and other species. Calcitonin inhibits bone loss through the suppression of osteoclast activity. Salmon calcitonin is approximately 40-50 times more potent than natural human calcitonin at inhibiting osteoclast function. It can be obtained naturally from salmon or can be synthesised with the same chemical structure. Calcitonin was originally available only as an injectable formulation, but in recent years more convenient formulations have become available. Unigene is actively seeking to license its intranasal calcitonin product in Europe and other territories outside the US. nigene licensed its intranasal calcitonin product to Upsher-Smith Laboratories in December 2002, under a $US10 million exclusive US licensing agreement. Under the terms of the agreement, Unigene received an upfront payment of $US3 million from Upsher-Smith and will be eligible to receive milestone payments and royalty payments on product sales. Unigene will be responsible for manufacturing the product at its Boonton facility in New Jersey, USA, and will sell finished calcitonin product to Upsher-Smith. Upsher-Smith will package, market and distribute the product nationwide. Unigene granted an exclusive license to Faran Laboratories in September 2003 for its intranasal calcitonin osteoporosis product in Greece. Unigene will sell the finished product to Faran, who will promote and market it throughout the country after Unigene obtains European regulatory approval and local pricing approval. Unigene will receive an upfront payment and is eligible to receive milestone payments prior to product launch. Faran will pay Unigene a fixed price for each unit of product received. Qingdao General Pharmaceutical Company was a licensee for Unigene's injectable and intranasal calcitonin products in the People's Republic of China, and Unigene had received initial payments from Qingdao General Pharmaceutical in 1996. However, in June 2000, Unigene announced that it has entered into a joint venture with Shijiazhuang Pharmaceutical Group Company for the manufacture and distribution of injectable and intranasal calcitonin for the treatment of osteoporosis in China. Unigene initially will be responsible for supplying bulk calcitonin manufactured in its production facility in New Jersey and the joint venture will be responsible for filling, packaging, promoting and marketing the products. Unigene owns 45% of the contractual joint venture. Unigene is also developing oral and injectable formulations of calcitonin. In January 2004, Unigene announced it had received an approvable letter from the US FDA to market its calcitonin intranasal spray for the treatment of osteoporosis. The letter indicates that the FDA will approve the NDA upon finalisation of the labelling and resolution of specific remaining issues, including the submission of additional information and clinical data. Unigene filed the NDA in March 2003. Using the results from a pilot study completed in the UK, Unigene filed an IND with the FDA and began clinical testing of this intranasal calcitonin in the US. Clinical studies were successfully completed by year end 2001, demonstrating significant bone marker activity and similar serum concentrations between this product and that of an existing nasal calcitonin product. The European Union's regulatory authority, the Committee for Proprietary Medicinal Products (CPMP), has confirmed the efficacy of calcitonin formulations for the treatment of postmenopausal osteoporosis and other bone disorders. The CPMP has recommended revisions to and harmonisation within the European Union of the authorised indications for calcitonin formulations. The CPMP has determined that authorised indications for intranasal calcitonin will be approved for "treatment of established post-menopausal osteoporosis in order to reduce the risk of vertebral fractures", and new prescribing information will clarify that intranasal calcitonin does not appear to reduce the number of hip fractures. These recommendations will be implemented in the near future and will eliminate discrepancies between countries and between formulations. The Chinese regulatory authorities have granted Unigene an import license for calcitonin, and Unigene and Shijiazhuang have submitted an NDA in China. If this NDA is approved, the joint venture will have up to 6 years' market exclusivity for intranasal and injectable calcitonin. Unigene was granted a US patent for the intranasal formulation of calcitonin in 2002.