Ash 2017 – Blueprint nips at Rydapt’s heels

Rydapt has only been on the market for seven months, and already Novartis needs to worry about competition in at least one of its indications. Blueprint Medicines’s BLU-285 is emerging as a more potent agent, with early data pointing to a greater response in patients with advanced systemic mastocytosis.

This is a good result for Blueprint, which went from a Nasdaq float on preclinical data to an Ash plenary presentation in the space of two and a half years. Bullish sales forecasts have already been attached to BLU-285, although on the back of these data it would not be surprising to see them rise.

Your old KIT bag

BLU-285, known now by the generic name avapritinib, is a selective inhibitor of c-KIT. The KIT D816v mutation is common in systemic mastocytosis patients, making this a sensible target – Rydapt inhibits c-KIT, but also FLT3 and several other kinases.

The data presented at Ash with BLU-285 came from a phase I trial that tested doses between 30mg and 400mg per day – 300mg has been selected for phase II. Although efficacy endpoints were not the primary goal of the trial, researchers evaluated them, and said complete or partial responses were achieved in 10 of 18 patients, or 56%.

With small numbers in this trial, this high remission rate might not hold in phase II and III studies. However, the across-study comparable number for Rydapt was 21%, so BLU-285’s efficacy could decline somewhat and still represent an improvement.

Advanced systemic mastocytosis affects only 2,600 patients a year in the US. Blueprint has now extended the dosing trial to include patients with smouldering disease, which represents another 1,800 patients, as well as the very rare mast cell leukaemia.

Dr Daniel DeAngelo, associate professor of medicine at Harvard Medical School, said Rydapt’s launch had resulted in more diagnoses of systemic mastocytosis as patients presenting with skin lesions or anaphylactic reactions have been tested for the disease.

However, he added that this drug carries with it a significant toxicity burden – 82% of patients suffered from nausea in that setting, and 60% anaemia, for example – requiring significant dose modifications and prophylactic use of anti-emetics. “It’s not a trivial agent to administer,” Dr DeAngelo said.

Of 32 patients who have been treated with BLU-285, nine, or 28%, have reported nausea and nine anaemia.

To a billion and beyond

BLU-285 is Blueprint’s lead asset, and is also being tested in another KIT-driven disease, gastrointestinal stromal tumours.

EvaluatePharma’s consensus of sellside analysts puts 2022 sales at $321m, with roughly half assigned to each indication.

Rydapt’s 2022 forecast is $614m. Novartis has not disclosed sales from its first few months on the market, which might give some clues to the size of the opportunity, although any readthrough to BLU-285 will need to be treated with caution since Rydapt is also approved in acute myeloid leukaemia.

Blueprint’s investors should see nothing to discourage them. But after nearly quadrupling in valuation to $2.8bn since its IPO in 2015, the group is looking on the pricey side. On the other hand, the scarcity of unpartnered phase II oncology projects means that business development opportunities, even at such levels, do not seem in the least implausible.

To contact the writer of this story email Jonathan Gardner in Atlanta at [email protected] or follow @ByJonGardner on Twitter

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