Welcome to your weekly digest of approaching regulatory and clinical readouts. Developing novel therapies for type 1 diabetes has proved difficult, but this has not stopped Novo Nordisk from trying. The Danish company is due to report results this quarter from a phase II trial of its anti-IL-21 monoclonal antibody NN9828.
Insulin is used to manage type 1 diabetes, but patients can still find it hard to keep their glucose levels within the normal range, and pharma companies continue to look for new options.
NN9828 is designed to preserve the insulin-producing beta cells that are destroyed in type 1 diabetes, so even if it were to be successful it would halt disease progression at best, rather than representing a cure.
This approach has fallen short before, with Caladrius recently failing to show a benefit with its T regulatory cell candidate CLBS03 (Caladrius refuses to give up on Tregs for diabetes, February 22, 2019).
The projects are designed to prevent the autoimmune reaction seen in type 1 diabetes, albeit in different ways. Caladrius’s Tregs are thought to damp down the immune system broadly while, by hitting IL-21, NN9828 could stop the development of autoreactive T cells that drive the disease, Novo hopes.
Still, catching patients early enough could be a problem. Like Caladrius, Novo is taking aim at newly diagnosed subjects, but even in this population the damage might already have been done.
In the phase II study patients are receiving 12mg/kg NN9828 intravenously every six weeks, with or without a daily subcutaneous injection of Novo’s marketed type 2 diabetes drug Victoza; there is also a placebo cohort. Patients in all groups have continued insulin therapy. The primary endpoint is preservation of stimulated C-peptide, a marker of residual insulin production, at one year.
Analysts are not expecting much from NN9828: sellside consensus forecasts put 2024 sales at just $24m, according to EvaluatePharma. Novo is also working on stem cells to treat type 1 diabetes, but these efforts are some way from the clinic.
The lion’s share
Meanwhile, Aslan Pharmaceuticals’ primary focus is on varlitinib’s pivotal trial data in biliary tract cancer in the second half, but investors also have an earlier catalyst to look forward to: ASLAN003 is in a phase II acute myelogenous leukaemia study, the first part of which is due to read out by mid-2019.
This first part concerns four six-patient cohorts of ascending ASLAN003 monotherapy doses over a 28-day cycle until relapse or toxicity. The second will combine the optimal dose with azacitidine, and overall the study aims to recruit 56 relapsed/refractory subjects. The study’s primary efficacy measure is overall response rate.
At its most recent update Aslan said the third cohort, dosing at 100mg twice daily, had been completed. But efficacy is elusive: one subject remains on treatment with stable disease, with a reduction in bone marrow blasts from 38% to 22% at four months, while a presentation at Ash in December revealed that two patients had discontinued after their AML progressed.
If the best that ASLAN003 has been able to achieve so far is a stable disease then investors must hope that the highest dose can put some patients into remission, without causing unsustainable toxicity.
ASLAN003 is one of a new generation of DHODH inhibitor anticancers that also includes Bayer’s BAY2402234 and Agios’s AG-636. These are supposed to be more potent than leflunomide and teriflunomide, which are thought to have activity at DHODH but are marketed for autoimmune conditions.
Aslan, a Singapore-based company, has a lot riding on the readout. Its recent restructuring cited ASLAN003, along with varlitinib and the atopic dermatitis project ASLAN004, as a strategic priority.
|Selected DHODH inhibitors|