Kynamro might have struggled to persuade regulators and failed to live up to commercial expectations once it reached the market, but it being the first antisense drug to be launched successfully has helped spur interest in the technology.
AstraZeneca’s expansion of its collaboration with Kynamro's originator, Isis Pharmaceuticals, was at least the third transaction this year in antisense, and at $65m up front was one of the richer deals ever signed (see tables below). This RNA-manipulating approach still has much to prove, but now pharma talent scouts appear to be on the lookout for the next prospect.
It might not hurt the cause of antisense that Kynamro, which interferes in the coding for the apo B-100 protein, proved successful in a phase III trial in patients with heterozygous familial hypercholesterolemia. If the data announced yesterday can persuade regulators to expand the label beyond the small homozygous population in which the drug is now indicated this could improve the sales outlook.
A look at deals in recent years on antisense programmes shows how prolific Isis has been – pacts with six different big pharma partners have been agreed, led by the $175m it received up front from Genzyme, now part of Sanofi, for rights to Kynamro.
However, for all of Isis’s work, it has fallen short in terms of its ability to seal the biggest deal. This honour belongs to Nogra Pharma, which received a chunky $710m from Celgene for rights to the Crohn’s disease project mongersen (Celgene Crohn’s focus turns to phase III, October 20, 2014).
|Notable product-specific antisense deals|
|Product||Originator||Company||Deal date||Up-front payment ($m)||Value ($m)|
|Mongersen||Nogra Pharma||Celgene||24 Apr 2014||710||2,575|
|Kynamro||Isis Pharmaceuticals||Sanofi||7 Jan 2008||175||1,900|
|ISIS-FXIRx||Isis Pharmaceuticals||Bayer||4 May 2015||100||375|
|MGN-1374/MGN-9103||miRagen Therapeutics||Servier||18 Oct 2011||45||1,000|
|AZD9150/ ISIS-STAT3-2.5Rx||Isis Pharmaceuticals||AstraZeneca||11 Dec 2012||31||271|
|Nusinersen||Isis Pharmaceuticals||Biogen||4 Jan 2012||29||299|
|ATL1103||Antisense Therapeutics||Cortendo||14 May 2015||3||110|
But still, Isis has done very well for itself in the deal-making front, which befits a group that has got one candidate to market and three more to phase III. The Astra transaction announced yesterday, for example, expands an existing tie-up, which gives the UK group rights to asssets in cardiovascular, metabolic and renal diseases.
Earlier this year Bayer paid $100m up front for rights to anticoagulant ISIS-FXIRx (Isis snags Bayer in quest for anticoagulant Holy Grail, May 5, 2015). And in 2012 Biogen and Isis began a multi-part collaboration that has yielded a late-stage project in the spinal muscular atrophy agent nusinersen.
Partnership for some, takeouts for others
But, as Nogra proves, Isis has been visible but has not been alone in eliciting interest from bigger partners. Miragen signed over rights outside the US and Japan to Servier for candidates in cardiovascular and muscle disease, a 2011 alliance that has produced MGN-1374 and MGN-9103. The two groups said last year that the collaboration had been extended through 2016, to fund those projects through phase II.
|Notable research alliances|
|Antisense company||Partner||Deal date||Up-front payment ($m)||Deal value|
|Isis Pharmaceuticals||AstraZeneca||3 Aug 2015||65||NA|
|Isis Pharmaceuticals||Biogen||10 Dec 2012||30||230|
|Santaris Pharma||Roche||9 Jan 2014||10||148|
And, as if to demonstrate a potential endgame for all these negotiations, Roche’s takeout of Santaris Pharma only a few months after striking a research collaboration shows that many big pharma groups want access to these technologies (Roche senses rival influences and strikes for Santaris, August 5, 2014).
It is interesting to note a gap in dealmaking between 2012 and 2014. This coincides with Kynamro’s approval and launch, suggesting that many in the sector were waiting to see whether the novel approach could get past regulators and show commercial strength.
Now with numerous partnered projects at the middle and late stages of clinical development, and Roche having taken a company’s discovery platform entirely in-house, a greater day of reckoning seems to be approaching for antisense. The next phase III trials for Isis assets are due to read out in 2016 and 2017, and will be a sign of whether the partnership funding has been money well spent.