Date: 2017-08-11
Type of information: Licensing agreement
Compound: antisense drugs including inotersen and IONIS-FB-L Rx
Company: GSK (UK) Isis Pharmaceuticals (USA - CA), now Ionis Pharmaceuticals (USA - CA)
Therapeutic area: Rare diseases - Infectious diseases - Ophtalmological diseases
Type agreement: licensing - development - commercialisation
Action mechanism: antisense drug. Antisense therapies target the proteins involved in disease processes through the RNA that is involved in building these proteins. The Isis discovery platform develops specific therapies that bind to messenger RNA (mRNA) and inhibit the production of disease-causing proteins. Isis recently announced data from a Phase 3 trial in heterozygous familial hypercholesterolemia patients that demonstrated the therapeutic effect of this approach
- IONIS-FB-LRx is a ligand conjugated antisense (LICA) drug in development for the treatment of complement-mediated diseases. In a Phase 1 study completed earlier this year, IONIS-FB-LRx achieved dose-dependent reductions in plasma factor B (FB) and demonstrated a safety and tolerability profile that supports further clinical development. Ionis plans to initiate the first Phase 2 study with IONIS-FB-LRx in patients with dry age-related macular degeneration (AMD) later this year, and studies in other indications in 2018.
- Inotersen (IONIS-TTRRx) is a generation 2.0+ antisense drug Ionis is developing for the treatment of patients with TTR amyloidosis (ATTR). Inotersen is administered once weekly as a single 300 mg subcutaneous injection. Ionis designed inotersen to inhibit the production of all forms of TTR protein, including both the hereditary and wild-type forms, offering a unique approach to treat all types of ATTR. Inotersen has demonstrated sustained and robust TTR reductions in clinical studies in different populations of patients with ATTR.
Ionis has successfully completed the Phase 3 NEURO-TTR study with inotersen in patients with polyneuropathy due to hereditary TTR amyloidosis (hATTR-PN). Ionis plans to file for marketing approval of inotersen in the U.S. and EU in the second half of 2017. The Company also plans to present results from the NEURO-TTR study at an upcoming medical meeting and to submit results from the study for publication in a peer-reviewed medical journal.
The U.S. Food and Drug Administration has granted Orphan Drug Designation and Fast Track Status to inotersen for the treatment of patients with familial amyloid polyneuropathy. The European Medicines Agency has granted Orphan Drug Designation to inotersen for the treatment of patients with TTR amyloidosis.
Disease:
Details:
- • On March 31, 2010, GSK and Isis Pharmaceuticals announced a new strategic alliance that will apply the Isis antisense drug discovery platform to seek out and develop new therapeutics against targets for rare and serious disease, including infectious diseases and some conditions causing blindness. This alliance provides GSK with access to Isis’ expertise in drug discovery and development of RNA-targeted therapeutics, with Isis retaining responsibility for the discovery and development of compounds to the alliance targets from inception to PoC.
Financial terms:
- Under the terms of the agreement, which covers up to six programmes, Isis will receive an upfront $35 million payment from GSK and is eligible to receive on average up to $20 million in milestones per programme up to Phase 2 proof of concept (PoC). GSK will have the option to license compounds at PoC, and will be responsible for all further development and commercialisation. Isis will be eligible to receive license fees and milestone payments, totaling nearly $1.5 billion, in the event all six programmes are successfully developed for one or more indications and commercialised through to pre-agreed sales targets. In addition Isis will receive up to double-digit royalties on sales, from any product that is successfully commercialised.
Latest news:
- • On August 11, 2017, Ionis Pharmaceuticals reported that the company has retained all rights to inotersen and IONIS-FB-LRx. As part of a reprioritization of its pipeline and strategic review of its Rare Diseases business, GSK declined its options on both drugs. Ionis plans to file for marketing authorization for inotersen this year to support a commercial launch of inotersen in 2018. Inotersen is designed to treat patients with TTR amyloidosis. The first indication Ionis is pursuing for inotersen is to treat patients with polyneuropathy due to hereditary TTR amyloidosis .Ionis completed the Phase 3 NEURO-TTR study of inotersen in which the drug demonstrated significant benefit on both primary clinical endpoints of neurological disease progression and quality of life in patients with hATTR-PN.
- Ionis Pharmaceuticals is now considering several options including formaiton of a commercial subsidiary to commercialize or co-commercialize inotersen in North America. The company is also accelerating the expansion of its TTR program for patients with cardiomyopathy due to TTR amyloidosis and the development of its LICA follow-on drug.
- IONIS-FB-LRx is a ligand conjugated antisense (LICA) drug in development for the treatment of complement-mediated diseases. In a Phase 1 study completed earlier this year, IONIS-FB-LRx achieved dose-dependent reductions in plasma factor B and demonstrated a safety and tolerability profile that supports further clinical development. Ionis plans to initiate the first Phase 2 study with IONIS-FB-LRx in patients with dry age-related macular degeneration (AMD) later this year, and studies in other indications in 2018.
- GSK, consistent with its focus on treatments for infectious diseases, continues to advance two drugs targeting hepatitis B virus (HBV) under its collaboration with Ionis: IONIS-HBVRx and IONIS-HBV-LRx. GSK is currently conducting Phase 2 studies for both drugs.
Is general: Yes
