Global Blood’s sickle cell approval is no guarantee of success

Rather than nipping at Adakveo’s heels, Global Blood Therapeutics’ newly approved sickle cell drug Oxbryta might end up floundering in the Novartis product’s wake.

On the surface it might seem that any first-mover advantage Novartis had after the early approval of its sickle cell treatment Adakveo last week has been eliminated by yesterday’s nod for Global Blood Therapeutics’ Oxbryta (voxelotor).

The US regulator green-lit the once-daily pill three months early, saying the drug could give “additional hope” to the 100,000 people in the US who live with the blood disorder. But questions still remain around Oxbryta's impact on long-term outcomes, and a large number of on-drug patients failed to show any benefit. Perhaps Novartis does not have too much to worry about.

Is good good enough?

Oxbryta was approved on the basis of increased haemoglobin response in patients, defined as an increase of more than 1g/dl following 24 weeks’ treatment. However, only 51% of patients in the Hope trial who took the maximum 1.5g dose of Oxbryta met the haemoglobin improvement threshold.

Harder endpoints that could have backed up Oxbryta's effectiveness were removed from the Hope trial after disappointing data in an early cut of the study; these included measures of quality of life and rates of vaso-occlusive crises. This was seen as a risk, but the company argued that the long-term benefits of increasing a patient's haemoglobin levels – thought to include a reduced risk of stroke and organ damage – would be enough to win approval (Global Blood launches bold bid for early sickle cell approval, 27 June 2018).

US regulators were obviously convinced, though Global Blood might find a tougher audience when it comes to the payers. 

Two drugs better than one?

Industry bulls might be tempted to argue that given the two drugs’ different mechanisms of action they could be used in combination: Oxbryta to improve haemoglobin levels and Adakveo to stop the painful vaso-occlusive crises associated with the disorder, where it gained approval last week.

Most sickle cell sufferers, however, go to hospital emergency rooms because of vaso-occlusive crises, so Oxbryta’s less-than-clear benefits might make it hard to convince payers of the advantages of combining two drugs. These have respective annual price tags of up to $113,000 for Adakveo and $125,000 for Oxbryta.

And while discounts would cut Oxbryta’s price to $100,000 a year, according to Global Blood executives, the drug's commercial potential could seriously disappoint if patients do not experience benefits in the real world. 2024 sellside consensus revenue forecasts collected before these agents' approvals sat at $1.58bn for Oxbryta, against $360m for Adakveo, according EvaluatePharma.

Hanging on

Achieving those sales also relies on Oxbryta staying on the market. The drug only has conditional approval, so will have to succeed in a confirmatory trial. But even here the study will only measure a surrogate endpoint – transcranial doppler flow velocity, which indicates a patient’s risk of stroke according to blood flow in the brain – rather than hard data on stroke reduction.

It could be argued that the FDA has given Global Blood an easy ride here, and given the unmet need in sickle cell this is perhaps understandable. Payers are unlikely to be so lenient, however, particularly when a competitor with an easily measured benefit is available. 

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