IBT favourite Array updates trial results ahead of key FDA decision
Array Biopharma (ARRY), a top ten holding for LSE-listed International Biotechnology Trust (IBT), has reported positive results from a safety lead-in phase of a pivotal trial of a triplet therapy comprising two of its drugs – binimetinib and encorafenib – with Merck KGaA’s Erbutix in BRAF mutant colorectal cancer (CRC). The news comes a few days ahead of the expected completion of the FDA review – and possible first approval – of the binimetinib/encorafenib combination in BRAF-mutant melanoma on 30 June. Array was the fifth largest holding for IBT at the end of May, accounting for 4.0% of its NAV.
Array reported over the weekend that in the 29-patient lead phase to its pivotal trial in CRC dubbed “Beacon CRC”, median overall survival (mOS) has not been reached at 12.6 months of follow-up (so more than half of the patients still remain alive after this time). This is almost double what would be expected for the patients on standard therapies (mOS for chemotherapy + Erbitux is less than six months) and still has the potential to increase. Overall response rate (ORR) and median progression free survival (PFS) have been previously reported from this sub-study at 48% and 8 months respectively, both of which are well above the historical standard of care (of <10% and ~2 months, respectively).
Beacon CRC is evaluating the efficacy and safety of encorafenib, binimetinib and cetuximab in patients with BRAF-mutant metastatic CRC whose disease has progressed after one or two prior regimens. It is the first and only Phase III trial designed to test a BRAF/MEK combo in BRAF-mutant advanced CRC. 30 patients were treated in the safety lead-in and received the triplet combination, 29 of which had a BRAFV600E mutation. MSI-H, resulting from defective DNA mismatch repair, was detected in only 1 patient.
The completion of the FDA review of bini/enco later this week is an important near-term stock price catalyst for Array, although it is widely assumed among sell-siders that the combination will be approved. The doublet combines a B-raf inhibitor (encorafenib, expected to be known as Braftovi) with a Mek inhibitor (binimetinib or Mektovi) and will potentially be the third such combination to market after drug pairings from Novartis (Tafinlar + Mekinist) and Roche’s (Zelboraf + Cotellic). Array intends to market its drug pairing against these giants, but has a potential advantage in terms of efficacy and side effect profile.
Later this year, the company will see some initial data from a study testing combinations of binimetinib with Bristol-Myers Squibb’s Opdivo with/without Yervoy in patients with CRC where the tumour is microsatellite stable. This may show whether there is activity for one of these combinations in CRC patients, who do not respond to checkpoint inhibitors (Opdivo is approved for use in microsatellite unstable CRC). The main longer-term catalyst for the company, however, remains the outcome of the Beacon study, which may potentially occur in 2019. Array is in discussions with regulators about the possibility of using PFS or another endpoints to support earlier filing for approval.
IBT favourite Array updates trial results ahead of key FDA decision