Roche Ramps Up Cancer Portfolio With $1.7bn Ignyta Buy
Executive Summary
The Swiss giant's acquisition of Ignyta to get hold of the latter's closely-watched NSCLC drug entrectinib will potentially trigger an intriguing fight for market share in the near future with Loxo Oncology and Bayer's larotrectinib.
The holiday season is going to be a very happy one for Ignyta Inc. following the news that Roche is paying $1.7bn to acquire the San Diego-based rare cancer specialist.
Under the terms of the deal, which has been agreed unanimously by the boards at both companies, the Swiss major is paying $27 per share which represents a premium of 74% on Ignyta's closing price on Dec. 21 and 89% over on its average stock price over the past 90 days. In return, Roche is getting its hands on entrectinib, which Ignyta has claimed could be a best-in-class therapy for non-small cell lung cancer (NSCLC) patients.
Entrectinib is a tyrosine kinase inhibitor being developed for tumors that harbor NTRK or ROS1 fusions – the latter occur in about 2% of all NSCLC cases. In October, interim data presented at the World Conference on Lung Cancer in Yokohama from the Phase II STARTRK-2 trial in patients with ROS1 fusion-positive advanced NSCLC revealed that entrectinib demonstrated a 78% (25 out of 32) and 69% (22 out of 32) confirmed objective response rate (ORR).
The drug also showed a median duration of response of 28.6 months and median progression free survival (PFS) of 29.6 months in this population, with 53% of patients remaining on the study. Importantly, in terms of activity in the central nervous system, entrectinib showed 83% (five out of six) confirmed intracranial ORR in patients with measurable brain metastases.
With over 200 patients treated at the recommended Phase II dose, most adverse events were Grade 1-2 and reversible, and only 3% of patients discontinued from the study due to treatment-related side effects. With its duration of response, PFS data times and its ability to cross the blood-brain barrier, Ignyta believes entrectinib, which has PRIME designation from the EMA and breakthrough therapy designation from the US FDA, has the potential to be used as a first-line targeted therapy for patients with ROS1-positive NSCLC.
If approved, and Ignyta is hoping for a tissue-agnostic label, entrectinib would compete with Pfizer Inc.'s Xalkori (crizotinib), which is approved for ROS1+ NSCLC but has poor CNS penetration. Another product, Pfizer’s lorlatinib, which is an ALK and ROS1 inhibitor with CNS activity, is in Phase II.
Another potential rival that will have watched the link-up with Roche with great interest will be another company looking at tissue-agnostic cancer therapies, Loxo Oncology Inc. Last month, the firm signed an agreement with Bayer AG, including a hefty $400m upfront fee, to develop and commercialize its NTRK inhibitor larotrectinib – this week (Dec. 20), Loxo initiated a rolling submission of its NDA for the latter to the US FDA for the treatment of TRK fusion cancers. (Also see "Loxo's Larotrectinib Requires Paradigm-Change In Clinical Practice" - Scrip, 5 Jun, 2017.)
Ignyta, which raised $160m after issuing 10m shares in a public offering in October, says it has an 'Rx/Dx approach' to development, combining precision therapeutics and in-house molecular diagnostics. Its pipeline includes taladegib, a small-molecule hedgehog pathway inhibitor which is in Phase Ib trials for ovarian cancer, RXDX-105, a RET inhibitor also in Phase Ib in patients with advanced lung cancer and other solid tumors, and RXDX-106, a pseudo-irreversible inhibitor of the TAM (TYRO3, AXL, and MER) family of receptor tyrosine kinases which is currently in late-stage preclinical development.
As for Roche, its pharmaceuticals chief Dan O’Day said in a statement that “cancer is a highly complex disease and many patients suffer from mutations which are difficult to detect and treat." He added that the Ignyta acquisition "builds on Roche’s strategy of fitting treatments to patients" and will allow the company "to broaden and strengthen its oncology portfolio globally.”
The deal comes at a time when Roche is preparing for a battering from biosimilar competition to some of its big-selling cancer therapies. MabThera/Rituxan (rituximab) is already suffering market share erosion in Europe and rivals to Herceptin (trastuzumab) and Avastin (bevacizumab) are lining up. (Also see "New Drugs Shine But Biosimilars Blunt Roche Revenue Rise" - Scrip, 19 Oct, 2017.)
Datamonitor Healthcare analyst Ali Al-Bazergan told Scrip that with the deal, Roche continues to focus on its bolt-on strategy to complement its oncology portfolio. He added that entrectinib "brings in an extremely promising multi-targeted NTRK/ROS1/ALK inhibitor" which is on track for dual NDA submissions in both the NTRK tissue-agnostic and the ROS1-positive NSCLC indications in 2018.
Al-Bazergan added that Bayer’s partnership with Loxo for laratrenctinib "strengthens the market opportunity for entrectinib" and also "paves the way towards a best-in-class profile owing to strong results in the Phase II STARTRK-2 study with potential long-term differentiation coming from PFS and CNS activity."
Another company full of Christmas cheer following the Roche deal is Nerviano Medical Sciences SRL which licensed entrectinib to Ignyta in 2013. The Italian firm is eligible for royalties on the drug.