Roche returns to gene silencing with Santaris acquisition

Four years ago, Roche's decision to stop research on RNA interference (RNAi) was seen as a major setback for the field of gene-silencing medicines, but now the drug major has bought back into the game.

Roche has just announced a $450m deal to acquire Danish company Santaris Pharma, a specialist in a form of antisense therapy that switches off a gene by interacting with messenger RNA (mRNA) to block the production of the protein product for which it codes.

In 2010, Roche shied away from the related field of RNA interference, which employs slightly different technologies to achieve the same mRNA-blocking objective, although it stressed at the time this was a business decision and not a statement about the prospects of the therapeutic approach.

The Swiss drug major now says that Santaris' Locked Nucleic Acid (LNA) technology "has the potential to address difficult to treat diseases in a range of therapeutic areas." At the moment small molecule and biologic drugs are thought to be able to address only around 20 per cent of all the genes in the human genome, but any gene can theoretically be silenced using RNA therapeutics.

Buying Santaris brings Roche two LNA programmes in Phase II testing, including SPC2968 for hepatocellular carcinoma, which targets the Hif-1 alpha gene, and miraversen for treating hepatitis C virus (HCV).

The Danish company is also developing SPC2968 for ocular indications such as age-related macular degeneration (AMD) and has drugs in early-stage clinical trials for homozygous familial hypercholesterolaemia (HoFH), a rare and serious form of elevated cholesterol.

RNA-targeting medicines were held back for years by stability, delivery and toxicological issues, along with the selection of target indications based less on ease of development and more on the size of the potential market.

Isis Pharma's Vitravene (fomivirsen) for cytomegalovirus retinitis - was approved in 1998, but quickly found its market destroyed by the advent of combination antiretroviral therapy for HIV/AIDS, the patient group most affected by the opportunistic infection.

After a string of late-stage trial failures, it was 15 years later that Isis was able to bring the second antisense drug to market, debuting Kynamro (mipomirsen) for HoFH in 2013.

Roche is stumping up $250m upfront for Santaris, which will be renamed Roche Innovation Center Copenhagen, with another $200m in the offing if development milestones are reached. The deal is expected to close later this month.

This is the third pipeline-boosting acquisition to be announced by Roche in the last few weeks, coming after its $1.7bn deal to buy Seragon Pharmaceuticals and $350m purchase of gene sequencing specialist Genia.