Date: 2018-11-05

Type of information: Licensing agreement

Compound: vamorolone

Company: Actelion (Switzerland), now Idorsia (Switzerland) ReveraGen BioPharma (USA - MD)

Therapeutic area: Rare diseases - Genetic diseases - Neuromuscular diseases

Type agreement: licensing

Action mechanism:

  • steroid. Vamorolone is a new first-in-human steroidal drug that separates a number of subsactivities seen in traditional glucocorticoid drugs (transrepression, physicochemical membrane effects, synchronization of tissue remodeling). Glucocorticoids have potent anti-inflammatory activities, which are thought to be mediated by repression of the NF-?B (NF kappa B) inflammatory pathway (transrepression). NF-?B complexes are activated by multiple types of pro-inflammatory molecules and pathways (eg. TNF-mediated activation). Once activated, NF-?B receptors translocate to the cell nucleus, and then bind to specific DNA sequences (NF-?B elements) near pro-inflammatory genes and repress the action of NF-?B gene activation. NF-?B activation is recognized as one of the earliest molecular features of Duchenne muscular dystrophy. Vamorolone has been optimized to retain transrepression activities, and has similar NF-?B inhibition when benchmarked against prednisolone in muscle cells in vitro. Vamorolone has been shown to protect against membrane damage, suggesting that it could counter-act the membrane instability due to dystrophin deficiency in DMD. Vamorolone has received Orphan Drug Designation in both the US and Europe. ReveraGen is pursuing parallel clinical development for vamorolone in both the US and Europe.

Disease: Duchenne muscular dystrophy


  • • On November 3, 2016, Actelion and ReveraGen BioPharma, a privately held company engaged in the discovery and development of proprietary therapeutic products for neuromuscular and inflammatory diseases, announced  that they have entered into a license, collaborative development and commercialization agreement. By this agreement, Actelion has obtained an exclusive option to in-license ReveraGen's lead compound vamorolone for the treatment of Duchenne muscular dystrophy at two different stages in its development. Vamorolone is a novel compound that has the potential to preserve muscle function and prolong ambulation, without some of the known side effects associated with corticosteroids currently in use. This is important especially for very young patients with Duchenne, where glucocorticoid therapy is not appropriate due to these side effects, which include growth stunting and immune suppression. ReveraGen is pursuing parallel clinical development for vamorolone in both the US and Europe. Phase I clinical trials were completed in late 2015, funded through venture philanthropy contracts by organizations including the Muscular Dystrophy Association (USA), Joining Jack (UK), Duchenne Research Fund (UK) and Duchenne Children's Trust (UK). A Phase IIa program is currently underway to investigate the safety and efficacy of vamorolone in 4-7 year old steroid-naïve boys with Duchenne. The DMD clinical program is being developed and run by a collaboration between the CINRG group and Newcastle University (Kate Bushby and Michela Guglieri). A Phase IIb program is in the planning stage.

Financial terms:

  • To date Actelion has paid a total of $ 10 million to ReveraGen which has been expensed as R&D costs. Under the terms of the agreement Actelion will also support R&D activities up to a maximum amount of $ 1 million p.a. for the next three years. In addition, Actelion acquired an option to obtain the exclusive worldwide license rights on vamorolone at any time but not later than following the receipt of the Phase IIb study results. If the option is exercised, ReveraGen will be entitled to receive up to $ 165 million in development and regulatory milestones for the DMD indication and up to $ 190 million for three further indications depending on achievement of certain development, regulatory approval and commercialization milestones. Furthermore, Actelion will pay increasing tiered single- to double-digit royalties on the net sales of vamorolone.

Latest news:

  • • On November 5, 2018, Idorsia announced that it has maintained the collaborative agreement with ReveraGen to research and co-develop vamorolone, a non-hormonal steroid modulator currently investigated for the treatment of Duchenne muscular dystrophy. Following receipt of the clinical study report for the Phase 2a study with vamorolone, Idorsia will pay ReveraGen $ 15 million to maintain the agreement.
  • In addition, the parties have agreed to a new structure of the agreement which makes milestone payments more dependent on commercial success. Under the renegotiated terms, Idorsia will be entitled to exercise an option to obtain the exclusive worldwide license rights on vamorolone at any time, but not later than upon receipt of the Phase 2b study results for a consideration of $ 20 million (previously $ 30 million). If the option is exercised, ReveraGen will be entitled to receive regulatory and commercial milestone payments up to $ 75 million in the DMD indication (previously $ 120 million) and three new one-time sales milestone payments of up to $ 120 million. Furthermore, Idorsia has agreed to support R&D activities for an additional year with up to a maximum amount of $ 1 million until mid-2020.
  • Milestone payments for three additional indications remain unchanged at $ 190 million. There is no change to the royalty payments agreed where Idorsia will pay tiered single-digit to low double-digit royalties on the annual net sales of vamorolone.

Is general: Yes