Type of information: Development agreement
Compound: RNAi therapeutics including ALN-AT3, fitusiran, patisiran and ALN-TTRsc02
Company: Genzyme (USA - MA), a Sanofi company (France) - Alnylam Pharmaceuticals (USA - MA)
Therapeutic area: Rare diseases - Genetic diseases
Type agreement: development - commercialisation
Action mechanism: RNAi
Disease: rare genetic diseases including hemophilia A, hemophilia B
- • On January 13, 2014, Genzyme, a Sanofi company, and Alnylam Pharmaceuticals have announced that they have significantly expanded their strategic agreement to develop and commercialize treatments for rare genetic diseases. Genzyme will have significant rights to Alnylam’s portfolio of clinical and pre-clinical stage drug candidates. Alnylam will retain most product rights in North America and Western Europe, and will have significantly expanded development and commercial opportunities for its genetic medicine pipeline through Genzyme’s established global infrastructure in rare diseases.
- In 2012, Alnylam and Genzyme formed an exclusive alliance to develop and commercialize Alnylam’s lead product, patisiran, which is in Phase 3 development for the treatment of transthyretin (TTR)-familial amyloid polyneuropathy, a rare life-threatening disease that damages the nervous system. The expanded relationship between Genzyme and Alnylam includes the following components:
- - Genzyme will obtain expanded rights to patisiran. Under the original agreement from 2012, Genzyme had rights to commercialize patisiran in Japan and the broader Asia-Pacific region. This disease has a disproportionately high prevalence in these territories. Under the expanded agreement, Genzyme will now commercialize patisiran in all territories outside of North America and Western Europe, which are retained by Alnylam for their commercialization.
- - Genzyme will obtain rights to commercialize worldwide three products in Alnylam’s pipeline. Specifically, Genzyme and Alnylam will co-develop and co-commercialize ALN-TTRsc, a product currently in Phase 2 development for the treatment of familial amyloid cardiomyopathy, in North America and Western Europe, while Genzyme commercializes the product in the rest of world. Genzyme will also have the rights to two additional products after the completion of early clinical trials and will be able to choose between full global rights or co-commercialization rights, depending on the product.
- - Genzyme will have the option up until 2020, with the possibility of extension through the end of 2021,to develop and commercialize outside of North America and Western Europe all products being developed to treat rare genetic diseases from Alnylam’s pipeline. Alnylam retains its rights to co-develop and co-commercialize its genetic medicine pipeline in North America and Western Europe.
It's worth underlining that Alnylam Therapeutics has announced on January 12, 2014, the acquisition of Merck's wholly owned subsidiary Sirna Therapeutics, comprising intellectual property and RNAi assets including pre-clinical therapeutic candidates, chemistry, siRNA-conjugate and other delivery technologies. Under the agreement, in exchange for acquiring the stock of Sirna Therapeutics, Alnylam will pay Merck an upfront payment of $175 million in cash and equity ($25 million cash/$150 million in Alnylam common stock). In addition, Merck is eligible to receive up to $105 million in developmental and sales milestone payments per product, as well as single-digit royalties, associated with the progress of certain pre-clinical candidates discovered by Merck. Merck is also eligible to receive up to $10 million in milestone payments and single-digit royalties on Alnylam products covered by Sirna Therapeutics' patent estate.
- Finally, Genzyme will become a major Alnylam shareholder with a stake of approximately 12% percent through a $700 million investment at a price of approximately $80/share, which represents a 27% premium as compared to the average share price over the last 30 days. In addition, Alnylam will receive R&D funding, starting on January 1, 2015, for programs where Genzyme has elected to opt-in for development and commercialization. Further, Alnylam is eligible to receive milestones and royalties. This transaction has been approved by the boards of both companies, and is subject to customary closing conditions and clearances under the Hart-Scott Rodino Antitrust Improvements Act.
- Product royalties following the the strategic restructuring agreed in January 2018:
- Sanofi Genzyme and Alnylam will be eligible to receive tiered royalties of 15 to 30 percent on global net sales of ALN-TTRsc02 and fitusiran, respectively, upon approval and commercialization. Previously, these programs were subject to co-development and co-commercialization terms in the United States, Canada and Western Europe.
- For patisiran, Sanofi Genzyme will be eligible to receive royalties, increasing over time to up to 25 percent, on sales in territories excluding the United States, Canada, and Western Europe.
- Sanofi continues to have the right to opt into other Alnylam rare genetic disease programs for development and commercialization in territories outside of the United States, Canada and Western Europe, as well as one right to a global license.
- • On January 7, 2018, Sanofi and Alnylam Pharmaceuticals announced a strategic restructuring of their RNAi therapeutics alliance to streamline and optimize development and commercialization of certain products for the treatment of rare genetic diseases.
- Sanofi will obtain global development and commercialization rights to fitusiran currently in development for the treatment of people with hemophilia A and B. Global commercialization of fitusiran, upon approval, will be done by Sanofi Genzyme,. Alnylam will receive royalties based on net sales of fitusiran products. The restructuring will enable Sanofi to assume full responsibility for development and commercialization of fitusiran, including costs. However, during the anticipated transition period Alnylam will fund such costs. Alnylam intends to substantially complete the transition of fitusiran to Sanofi by mid-2018. Sanofi will pay Alnylam a milestone of $50 million following dosing of the first patient in the ATLAS Phase 3 program for fitusiran.
- Alnylam will obtain global development and commercialization rights to its investigational RNAi therapeutics programs for the treatment of ATTR amyloidosis, including patisiran and ALN-TTRsc02. Sanofi will receive royalties based on net sales of these ATTR amyloidosis products.
With respect to other products falling under the RNAi therapeutics alliance, the material terms of the 2014 Alnylam-Sanofi Genzyme alliance remain unchanged.
- Alnylam will fund all development and commercialization costs for patisiran and ALN-TTRsc02 going forward. There will be no additional milestones due to either company with respect to patisiran or ALN-TTRsc02.
- Sanofi intends to substantially complete the transition of its patisiran activities in regions outside the United States, Canada, and Western Europe, consistent with the original scope of its license rights to patisiran, by mid-2018.
- The transaction is subject to customary closing conditions and clearances, including clearance under the Hart-Scott Rodino Antitrust Improvements Act.
- • On November 14, 2016, Alnylam Pharmaceuticals announced that, pursuant to the companies' global alliance signed in January 2014 , Sanofi Genzyme elected to opt in to co-develop (through Sanofi R&D) and co-commercialize fitusiran, an investigational RNAi therapeutic for the treatment of hemophilia and rare bleeding disorders, in the United States , Canada and Western Europe . This expanded right is in addition to their previously exercised opt-in decision to develop and commercialize fitusiran in their rest of world territories. The opt in decision was based on recent promising interim clinical results from a phase 1 study of fitusiran presented at the World Federation of Hemophilia (WFH) in late July and additional data that will be presented at the American Society of Hematology (ASH) meeting in December. Alnylam is on track to initiate the fitusiran Phase 3 program in early 2017.
Alnylam and Sanofi Genzyme will now co-develop and co-commercialize fitusiran in the Co-Commercialization Territory (United States , Canada and Western Europe ), while Sanofi Genzyme will retain exclusive rights to develop and commercialize the product in the Sanofi Genzyme Territory (rest of world). Certain development and sales and marketing costs for fitusiran will be shared 50/50 between Sanofi Genzyme and Alnylam. In addition, Sanofi Genzyme will be required to make payments totaling up to $75 million upon the achievement of development and regulatory milestones for fitusiran. Upon the initiation of the first global Phase 3 clinical trial for fitusiran, Alnylam will earn a milestone payment of $25 million . Sanofi Genzyme also will be required to pay tiered double-digit royalties up to twenty percent on annual fitusiran net sales in the Sanofi Genzyme Territory. The companies will share profits equally in the Co-Commercialization Territory, where Alnylam expects to book product sales.
Sanofi Genzyme has elected not to opt in for ALN-AS1, an investigational RNAi therapeutic for acute hepatic porphyrias. The clinical dataset informing the Sanofi Genzyme decision consisted of Part A and Part B results from the ongoing ALN-AS1 Phase 1 study, recently presented at the Society for the Study of Inborn Errors of Metabolism (SSIEM) meeting in September. Based on this decision, Alnylam intends to develop and commercialize ALN-AS1 globally upon product approval. Alnylam will present initial results from Part C of the ongoing Phase 1 study at the ASH meeting in December.
- • On October 1, 2015, Alnylam Pharmaceuticals and Genzyme announced that Genzyme has elected to opt into Alnylam's investigational ALN-AT3 hemophilia program for development and potential future commercialization in territories outside of North America and Western Europe . This marks the first product from Alnylam's Genetic Medicines pipeline to which Genzyme has opted in since the formation of the companies' global alliance in January 2014 , and the third product opt-in overall. Genzyme's opt-in decision was based on encouraging clinical data from the Phase 1 trial of ALN-AT3, including positive interim data that were presented at the International Society on Thrombosis and Haemostasis (ISTH) 2015 Congress in June 2015 .
- ALN-AT3 is the third Alnylam product for which Genzyme has exercised its opt-in right, the first two occurring at the close of the deal in early 2014 for patisiran and revusiran, investigational RNAi therapeutics for the treatment of transthyretin-mediated amyloidosis. In the case of ALN-AT3, Genzyme has elected presently to opt into the program for its ROW rights. Genzyme retains its future opt-in right to co-develop and co-promote ALN-AT3 with Alnylam in North America and Western Europe . Specifically, Genzyme has the right to either co-develop and co-promote ALN-AT3 in Alnylam's territory - with Alnylam maintaining development and commercialization control - or to maintain its ROW rights for ALN-AT3 and, if exercised by Genzyme, obtain a global license to ALN-AS1, Alnylam's investigational RNAi therapeutic for the treatment of acute hepatic porphyrias. Genzyme will exercise this selection right upon completion of human proof-of-concept for the ALN-AS1 program, which is expected to occur in 2016.