Two weeks after its stock started tanking, and one day after a run-of-the-mill quarterly earnings call, Glycomimetics confirmed the worst. A phase III trial of its lead sickle cell therapy, rivipansel, had failed, and it seems highly likely that the project is dead.
Shares in the company crashed 61% in early trade today, adding to the 29% of value that had ebbed away since mid-July. The curious timing of this collapse in confidence aside, there seems little remaining optimism for Glycomimetics’ approach. With a clinical pipeline based solely on selectin inhibition, rivipansel’s blow-up has understandably been taken as a bad omen.
Very little is actually known about the results at this stage. All that has been disclosed by the company and Pfizer, which licensed rivipansel back in 2011, is that the pivotal Reset study failed to meet primary and key secondary endpoints. Rivipansel was being tested in sickle cell patients hospitalised for a vaso-occlusive crisis, a period in which sufferers experience extreme pain; the partners had been hoping to show that the project could alleviate suffering, reduce opioid use and help patients leave hospital more quickly.
Until full results are published it is hard to say much more about rivipansel’s performance, but the tone of the statement suggests an unequivocal failure and the end of the partnership. The project always had its doubters – a prior phase II study failed, and the pivotal trial used a new primary endpoint and a novel setting – and many will conclude that this news only confirms rivipansel’s lack of activity.
Rivipansel is a pan-selectin antagonist; selectins are a family of adhesion molecules, and in sickle cell the aim was to reduce adhesion of red blood cells, making it harder for them to aggregate. Results from other projects in this area have been mixed.
While Modus Therapeutics’ sevuparin, which binds to P and L-selectin, failed in phase II earlier this year, Novartis has managed to show a reduction in vaso-occlusive crises with crizanlizumab, which binds exclusively to P-selectin, and is seeking regulatory approvals. However, sickle cell is considered an extremely tough disease to treat, and it seems likely that rivipansel was simply not potent enough to make a mark.
Glycomimetics’ entire clinical pipeline is based on similar technology. Its next project is uproleselan, which inhibits E-selectin. In blood cancers E-selectin is said to bind cancer cells within the bone marrow, the idea being that uproleselan can sensitise patients to chemotherapy by mobilising the cancer cells into the bloodstream.
A phase III trial is testing this hypothesis, seeking to recruit 380 patients with relapsed/refractory acute myeloid leukaemia, and due to yield topline results towards the end of 2020.
A phase I/II study generated median overall survival of 8.8 months, around three months longer than is typically expected in this population, according to the company. Supportive sellside analysts reckon that the pivotal study has a good chance of succeeding, largely because it allows more doses of uproleselan than have been tested previously.
Not everyone shares this view. Detractors point to a deterioration of the survival data seen in phase I/II, from presentations at Ash 2017 and Ash 2018. Others argue that the company’s claim that E-selectin expression correlates with overall survival is only weakly supported.
It will be some months before Glycomimetics can show whether its approach has any legs. Another asset, GMI-1359, which hits E-selectin and CXCR4, is due to start a phase Ib trial in breast cancer patients with bone metastases in the second half of the year, with data also due later in 2020.
However with the company’s market value falling to cash today, it is pretty clear that investors assume that Glycomimetics' platform is firing duds. Few seem willing to hang around and find out whether they are wrong.