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Agreements

Date: 2017-04-16

Type of information: Licensing agreement

Compound: inotersen and AKCEA-TTR-LRx, formerly IONIS-TTR-LRx

Company: Ionis Pharmaceuticals (USA - CA) Akcea Therapeutics (USA - CA), a subsidiary of Ionis Pharmaceuticals (USA - CA)

Therapeutic area: Rare diseases - Genetic diseases

Type agreement: licensing

Action mechanism:

  • antisense drug/antisense oligonucleotide. Inotersen is an antisense oligonucleotide designed to reduce the production of transthyretin to treat patients with TTR amyloidosis (ATTR), a severe, rare and fatal disease. In patients with ATTR, both the mutant and wild-type (wt) TTR builds up as fibrils in tissues, such as the peripheral nerves, heart, gastrointestinal system, eyes, kidneys, central nervous system, thyroid and bone marrow. The presence of TTR fibrils interferes with the normal functions of these tissues. As the TTR protein fibrils enlarge, more tissue damage occurs and the disease worsens, resulting in poor quality of life and eventually death.
  • Tegsedi™ has received marketing authorization approval from the European Commission (EC) for the treatment of stage 1 or stage 2 polyneuropathy in adult patients with hereditary transthyretin amyloidosis (hATTR amyloidosis). The drug  is also the subject of a pending new drug application in the U.S. and Canada. Tegsedi™ has a PDUFA date of October 6, 2018.
  • AKCEA-TTR- LRx has been designed to inhibit the production of transthyretin, the same protein inhibited by inotersen.  The compound is planned to enter clinical development in 2018.

Disease: hereditary transthyretin amyloidosis (hATTR)

Details:

  • • On April 17, 2018, Akcea Therapeutics and Ionis Pharmaceuticals announced the two companies have completed a transaction licensing the exclusive, worldwide rights from Ionis to Akcea for inotersen and AKCEA-TTR-LRx, formerly IONIS-TTR-LRx.  Inotersen is under regulatory review for the treatment of hereditary transthyretin amyloidosis. Akcea and Ionis are also developing AKCEA-TTR-LRx for hereditary and wild-type forms of ATTR and plan to commence clinical studies for AKCEA-TTR-LR in 2018.
  • The transaction was subject to certain closing conditions, including a non-waivable condition that the stock purchase agreement, the license agreement and related agreements and the transaction be approved by the affirmative vote of holders representing a majority of the issued and outstanding shares of common stock other than Ionis and its affiliates, which excluded a vote of Akcea’s directors and officers. This affirmative vote was obtained at a special meeting of Akcea stockholders on April 16, 2018..

Financial terms:

  • Under the agreement, Akcea paid Ionis an upfront licensing fee of $150 million through the issuance of 8,000,000 shares of common stock priced at $18.75 per share. Akcea obtained rights to commercialize inotersen and AKCEA-TTR-LRx globally. To support the incremental resources required for the launch of inotersen and to progress the clinical development program for ACKEA-TTR-LRx, Ionis purchased $200 million of Akcea common stock, or 10,666,666 shares, priced at $18.75 per share. Upon closing this transaction, Ionis' ownership in Akcea increased by 7%, from 68% to 75%, totaling 64,114,545 shares.
  • Regulatory approval of inotersen and AKCEA-TTR-LRx in the U.S. and EU will trigger milestone payments to Ionis of $50 million and $40 million, respectively, for each drug, with additional milestone payments due upon approval of both programs in various other geographies. The initial milestone payments may be payable in Akcea common stock at fair market value. Commercial profits and losses from inotersen will be split 60% to Ionis and 40% to Akcea until the first commercial sale of AKCEA-TTR-LRx, after which the profits and losses will be shared 50/50.
  • The costs of the development of AKCEA-TTR-LRx and the profits from its commercialization will be shared 50/50. The license for the two drugs also includes various sales milestone payments of up to nearly $1.3 billion.

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Is general: Yes