The French company Erytech is offering a novel approach to cancer treatment with Graspa, a red blood cell-encapsulated version of the chemotherapy drug L-asparaginase. The aim is to avoid the allergic reactions seen with older forms of the drug that are not encapsulated, with data in second-line pancreatic cancer due by the end of the first quarter.
In its lead indication, acute lymphoblastic leukaemia, the company took a knock last year when European regulators requested more data. With cash reserves running low any glimmers that Graspa works in pancreatic cancer, a notoriously difficult disease, would boost confidence.
|% of mkt cap||42%|
|Event||Phase II data, pancreatic cancer|
However, the scale of the challenge is illustrated by Jefferies analysts, who suggest that peak sales of $500m are possible in pancreatic cancer, though for now their base case assigns Graspa zero probability of success in this setting.
L-asparaginase works by breaking down asparagine, an essential nutrient for most tumour cell proliferation. It has been used since the 1970s as a cancer treatment in combination with chemotherapy, but is commonly associated with serious allergic reactions.
Graspa encapsulates it in red blood cells to reduce exposure to the immune system and hopefully reduce hypersensitivity. Encapsulation into donor blood uses osmotic stress that opens and closes pores in the red blood cell membrane; the blood is then transfused into the patient.
The phase II trial tests Graspa in 139 patients with progressive metastatic pancreatic cancer, in combination with either gemcitabine or the Folfox regimen versus standard of care alone. The primary measure is progression-free survival at 4 months.
The trial is being run in France, and enrolment was expanded from 90 patients to increase the powering of the study. Results are expected by the end of the first quarter.
In the trial patients are stratified according to their expression levels of asparagine synthetase, an enzyme that synthesises asparagine from asparatate; expression is low or absent in around 50-80% of metastatic pancreatic cancers. Tumour cells therefore have to get asparagine from blood plasma, but as this gets depleted by Graspa the tumours are essentially starved. Normal cells are capable of synthesising asparagine themselves.
In the phase I metastatic pancreatic cancer study in 12 patients Graspa monotherapy was well tolerated, with no dose-limiting toxicities.
Graspa is most advanced in relapsed or refractory acute lymphoblastic leukaemia (ALL), and was filed last year in Europe. In November the filing was withdrawn when the CHMP requested more data, including comparability data between old and new recombinant forms of asparaginase encapsulated in Graspa. Erytech shares fell 24% on the news, and a resubmission is expected by the middle of this year.
Graspa is also in a phase II US trial in ALL, and a European trial in AML. It is partnered with Recordati in Europe in both leukaemia indications and with Teva in Israel, and has orphan drug designations for all three indications in the EU and US markets.
Jefferies analysts forecast $25.5m Graspa sales by 2021, all assigned to the ALL indication (Asco-GI – Pancreatic cancer field awaits sparse data, January 24, 2017).
|Graspa peak sales, according to Jefferies analysts|
|ALL in US||120||70%|
|ALL in EU||40||90%|
Back in 2013 Erytech completed its Euronext IPO, raising €17.7m ($23m), and it also has a small American depositary receipt programme.
With just €37.7m in cash and a setback in its lead indication, a win in pancreatic cancer would help calm fearful investors. However, this looks like a herculean task.
|Graspa plus gemcitabine or Folfox, progressive metastatic pancreatic cancer||NCT02195180|