Global Blood aims for sickle cell dominance

Novo Nordisk’s interest in sickle cell disease, as signalled by last week’s deal for Epidestiny’s EPI01, is not as strange as it might appear. The company has made no secret of its desire to expand in rare blood-related diseases – hence its attempt to buy Ablynx. But Novo is late to the sickle cell party; Global Blood Therapeutics’ voxelotor is forecast to become the best-selling sickle cell disease therapy by 2022, while hopes are also high for Bluebird's gene therapy Lentiglobin.

A clue about whether voxelotor can live up to expectations will come this quarter with its first phase III data, from part A of the placebo-controlled Hope trial. Some analysts believe that positive results might be enough for accelerated US approval or could spur interest from big pharma.

This might be wishful thinking; it is more likely that a win in part A will simply increase the chance of overall success in the Hope trial, which is not due to yield final results until next year. This more measured view could be a reason why GBT’s stock has fallen back after surging in January on news of voxelotor’s breakthrough designation.

The initial readout from Hope will involve data from 150 patients out of a total 400. Part A of the trial is powered to show statistical significance on the primary endpoint, the proportion of patients responding; response is defined as a 1g/dl or greater increase in haemoglobin.

HC Wainwright analysts expect to see a response in 40-45% of voxelotor-treated patients, in line with the 46% observed in a phase I/II trial. It will also be important for the project to avoid any safety concerns at either dose being tested, 900mg or 1,500mg.

Although analysts are optimistic about the prospects for an early filing, GBT has said it plans to submit voxelotor to regulators after reporting results from part B of the study, due in the first half of 2019.

The results from part A will determine which dose is taken into part B. The initial phase of the trial will also be used to finalise the key secondary endpoint for part B, which would either involve measuring vaso-occlusive crises or patient-reported outcomes using an app developed by GBT.

If voxelotor does succeed in Hope and is subsequently approved it should see swift uptake in a disorder with few options. The FDA approval of Emmaus Life Sciences’s nutraceutical Endari last year, despite questions about its data package, highlights the desperation for new therapies.

Voxelotor, which is designed to address the underlying cause of disease by inhibiting abnormal sickle haemoglobin polymerisation, could have the edge over some other projects in development that only target crises, such as Pfizer and Glycomimetics’s rivipansel and Novartis’s crizanlizumab.

The unmet need in sickle cell disease, plus voxelotor’s convenient oral delivery and its potential as a disease-modifying treatment, could allow the drug to capture around 35% of the market and bring in peak US sales of $1.5bn, Morgan Stanley analysts estimate.

A rival is not too far behind in the form of Bluebird Bio’s Lentiglobin, which is also being tested in beta-thalassaemia. Bluebird expects to report data from its phase I HGB-206 sickle cell trial at this year’s Ash meeting, and could give more details on its registration plans by the end of the year. Given the inherent riskiness of gene therapy, Lentiglobin looks likely to come behind voxelotor in the treatment cascade, Needham analysts reckon. There is also the price question, which will be sensitive, with around 60% of sickle cell patients covered by Medicaid.

The analysts note that direct annual healthcare costs for sickle cell disease currently come to around $200,000 per patient per year, and suggest a price tag of around $100,000 per year for voxelotor. GBT plans to commercialise voxelotor itself, using around 75 US sales reps.

Novo’s Destiny

Meanwhile, EPI01, which is now in Novo’s hands, is further behind, having only completed phase I. The project, a combination of the chemotherapy drugs decitabine and tetrahydrouridine, is thought to work by increasing the amount of foetal haemoglobin, which could protect against the effects of defective sickle cell haemoglobin. 

Novo is not saying how much it paid up front for exclusive worldwide rights to EPI01, but the deal is worth up to $400m in total including development and sales milestones, suggesting that the initial fee was fairly small. Epidestiny has retained rights to the project in oncology.

There could be more deals to come in rare blood diseases, Novo’s chief executive, Lars Fruergaard Jørgensen, recently hinted to EP Vantage: “We’re looking at opportunities where we can leverage our infrastructure with haematologists. These haematologic diseases are rare in nature but typically still [affect] some thousands of patients.”

It should soon become apparent whether voxelotor holds promise – if it does, GBT might have sewn up the sickle cell sector before EPI01 even gets to the market.

To contact the writer of this story email Madeleine Armstrong in London at [email protected] or follow@ByMadeleineA on Twitter