Tolvaptan

Novartis has identified farabursen as a good fit for its burgeoning kidney disease portfolio.\n Novartis has committed another $1.7 billion to its ambition to become a kidney disease leader. The Swiss drugmaker is making the outlay, around half of which is upfront, to buy Regulus Therapeutics for a rare renal disease drug that is set to enter phase 3 in the third quarter.Regulus published top-line data from a phase 1b trial of its lead candidate, farabursen, in March. The trial enrolled patients with autosomal dominant polycystic kidney disease (ADPKD). People who received the oligonucleotide every other week for three months had statistically significant increases in urinary PC1 and PC2, proteins that inversely correlate with disease severity.Height-adjusted total kidney volume (htTKV), a predictor of renal insufficiency, increased 0.05% over four months in patients on farabursen. HtTKV grew 2.58% in the placebo cohort. Buoyed by the data, Regulus forged ahead with plans to start a phase 3 trial that could support a filing for accelerated approval.Novartis has identified farabursen as a good fit for its burgeoning kidney disease portfolio. The company has agreed to pay $7 a share upfront to acquire Regulus. The upfront payment, which amounts to $800 million, is more than double the closing price of Regulus’ stock Tuesday. Novartis has agreed to pay another $7 a share if Regulus achieves a milestone tied to the regulatory approval of farabursen. The total value, should all these targets be hit, would reach $1.7 billion.  Regulus has designed its phase 3 trial to support a filing for accelerated approval based on htTKV after 12 months. The trial will serve as its own confirmatory study, with the biotech tracking changes in a measure of kidney function, eGFR, out to 24 months to support full approval.If approved, farabursen will enter a market already served by Otsuka’s Jynarque. Otsuka said (PDF) U.S. sales “increased significantly” over the first three months of the year because ADPKD prescriptions rose. Regulus told investors in January that Jynarque is only used in about 7% of the addressable population, a fact the biotech’s CEO Joseph Hagan said is “in large part because of its safety and tolerability profile.”Regulus claimed farabursen is a multibillion-dollar opportunity. Novartis wants to seize the opportunity to advance the kidney care business that it has built out through deals such as the $3.2 billion Chinook Therapeutics acquisition and development of internal programs. The commercial portfolio now includes Fabhalta and Vanrafia. 

Novartis will pay $800 million upfront to acquire Regulus Therapeutics, a San Diego biotechnology company that launched nearly two decades ago with plans to make drugs capable of targeting small strips of nucleic acid known as microRNA.Announced Wednesday, the acquisition will hand the Swiss pharmaceutical firm a drug prospect called farabursen, which recently completed a Phase 1b study in people with autosomal dominant polycystic kidney disease, or ADPKD.Per deal terms, Regulus shareholders will receive $7 in cash per share, a premium of more than 100% to the stocks closing price Tuesday. Additionally, Novartis has committed to pay an additional $7 per share via a so-called contingent value right thats linked to the achievement of an unspecified regulatory milestone.Regulus was launched in 2007 as a joint venture between Alnylam Pharmaceuticals and Ionis Pharmaceuticals, building on a paper published in Nature on how a kind of synthetic oligonucleotide could silence microRNA, which plays a role in genetic regulation.After early successes, such as a 2010 partnership with Sanofi and a 2012 deal with AstraZeneca, the biotech hit setbacks from which it struggled to recover. It also had difficulty finding the right application for its drugmaking technology, trying its hand at a hepatitis C treatment that didnt pan out. Since 2021, Regulus shares have traded below $4 per share.The drug at the heart of its deal with Novartis, called farabursen, entered the clinic in 2022. Farabursen targets miR-17, which researchers have identified as potentially relevant to kidney disease.People with ADPKD have few treatment options, relying on the drug tolvaptan to slow the rate of kidney function decline, as well as pain relievers and blood pressure-lowering drugs.Acquiring Regulus is one of several investments Novartis has made in kidney disease, most notably a $3 billion deal in 2023 for Chinook Therapeutics that netted it Venrafia, which won accelerated approval to treat IgA nephropathy earlier this month. Its also developing Fabhalta, already cleared in IgAN, for several other kidney-related conditions.This is a meaningful addition to our renal portfolio as we continue driving innovation in kidney care, following our recent approvals of treatments for IgAN and C3G, Shreeram Aradhye, Novartis chief medical officer, wrote in a LinkedIn post.The pharma hinted earlier this year that it would continue to be active in dealmaking. Its president of biomedical research, Fiona Marshall, told BioPharma Dive that it was looking for early-stage assets. Novartis previously identified ADPKD as a target in its renal portfolio.So often, its having our own program that makes us really like the project, and then if we see somebody else is doing it better than us externally, well still bring that in, she said in January. '