Encouraging pivotal data from Erytech raise hopes that the French drug developer has managed to turn its red blood cell-encapsulating technology into a viable therapeutic.
Its lead project, Graspa, is encapsulated L-asparginase; the enzyme is widely used to treat childhood leukaemia but its toxicity means it cannot be tolerated by older or frailer patients. Phase III data released today show significantly fewer allergic reactions and non-inferior activity for Graspa, paving the way for a filing with European regulators next year.
The trial pitted Graspa against native L-asparginase, which is derived from Escherichia coli. Adding L-asparginase to chemotherapy has been shown significantly to improve remissions in acute lymphocytic leukaemia (ALL), but anything from 30% to 50% of patients develop allergic reactions. As a result it is almost exclusively used in children with ALL, who are more able to tolerate these effects.
L-asparginase works as an anticancer therapeutic because tumours rely on circulating asparagine for cell proliferation. Administering the enzyme, which breaks down asparagine, helps to starve the tumour.
Graspa avoids the side effects of this action because the degradation happens inside the red blood cells. The company has developed a technology to encapsulate the active agent within erythrocytes, which are then transfused into a patient.
The phase III data reported today showed a statistically significant reduction of allergic reactions: none of the 26 patients in the Graspa arm experienced a reaction versus 12 of the 28 in the reference group (p<0.001).
The second primary endpoint, to show non-inferior duration of asparaginase activity in non-allergic patients during the induction phase, was also hit; the data suggest that the encapsulated form works for longer with fewer doses.
The study enrolled 80 patients with relapsing or refractory ALL – both adults and children – into three arms. The first two compared Graspa with native L-asparaginse in patients without prior allergies, while the third was an open-label assessment of Graspa for patients who experienced allergic reactions in first-line treatment.
Erytech said that in the third arm, in patients with previous allergies, a “favourable” clinical profile was seen with only two patients experiencing mild allergic reactions.
Full data will be released at the Ash haematological cancer conference in December; efficacy in the adult and children subgroups will be of particular interest, given that the existing market for asparginase is primarily young people.
However, this initial data were encouraging enough to prompt a 14% jump in the company’s share price to €29.73, a record high. The stock floated in May 2013 at €11.60.
The company intends to file in the first half of next year in Europe, where it already has a marketing partner in Recordati. Rights in the US remain up for grabs; the project has orphan drug status in ALL in both regions.
Before these results, analysts at Credit Suisse who cover Recordati estimated global peak sales of $225m. That was based on the assumption that Graspa would capture about 15% of the market available in both AML and ALL.
However, Erytech estimates that 82% of patients with acute leukaemia are not treated with asparaginase owing to fears of toxicity, which points to greater potential.
The company will no doubt be hoping that potential US partners will also ponder this addressable market; a decision on its strategy in the world's biggest drug market is a hotly awaited event for Erytech's shareholders.
Recordati would be a logical partner. However, the terms of their European deal suggest a different structure might be preferable. Erytech is due to receive a big proportion any revenues on Graspa. The transfer price – Erytech will manufacture the drug – and royalties will see up to 45% of net sales paid to the French company, according to Credit Suisse.
If Recordati is interested in acquiring more of this product geographically, it might make sense economically to buy the company.