Ocrevus survives first brush with brain infection
The first case of a rare brain infection with Roche’s multiple sclerosis therapy Ocrevus should not cause too much alarm, with analysts putting it down to the patient's previous long-term treatment with Tysabri. However, any more incidents of progressive multifocal leukoencephalopathy (PML) could put a dent in the prospects of Ocrevus, which is expected to become the number-two MS drug by 2022 (see tables below).
For now, though, the risk of the infection appears to be much lower with Ocrevus than with Tysabri, which should help Roche’s product gain market share – assuming that PML does not turn out to be a bigger problem than currently thought.
|Top five MS drugs in 2022|
|Global sales ($m)|
|Aubagio||Sanofi||PDGF tyrosine kinase & DHODH inhibitor||1,433||2,248|
|Tysabri||Biogen||VLA 4 MAb||1,964||1,448|
The risk of PML is around 60-fold higher with Tysabri than with Roche’s cancer therapy Rituxan, which uses the same CD20-targeting mechanism as Ocrevus. Leerink analysts believe that Ocrevus could eventually end up with the same black-box warning as Rituxan on PML, but that this will make little difference to its adoption.
Indeed, MS patients have so far shown willingness to take the risk of PML in return for a highly effective treatment like Tysabri.
As far as efficacy goes, Roche seems to stack up well against other products available for relapsing-remitting MS, although the usual caveats about across-trial comparisons apply (Hidden gems emerge in ocrelizumab data, October 27, 2015). And Ocrevus is so far the only drug approved for primary progressive disease.
Similar efficacy and an apparently good safety profile – as well as a relatively convenient twice-yearly intravenous dosing schedule and a competitive price – have helped set high expectations for Ocrevus.
And it is Tysabri that is in line to suffer. Leerink analysts predict that Biogen’s product will lose 50% of its market share by the mid-2020s.
Both Tysabri and Tecfidera, also from Biogen, have seen their consensus forecasts shrink over the past year, according to EvaluatePharma.
But expectations for Ocrevus have also cooled, perhaps owing to the three-month delay in its approval and the cautious price point at which Roche launched (Roche prices Ocrevus for maximum disruption, March 29, 2017). Meanwhile, forecasts for Aubagio have jumped since Sanofi posted impressive growth with this product in its third quarter, no doubt helped by its strategy of positioning it on the lower end of the pricing spectrum for oral therapies.
|Biggest upgrades/downgrades to MS therapies|
|Product||Company||2022e sales ($m)||Change to forecast in 12 months ($m)|
Most analysts think that Tysabri is to blame for the latest case – the patient had reportedly been taking Biogen’s product for around three years and had only received one or at most two doses of Ocrevus. The patient was also said to be positive for the JC virus that, in immunocompromised individuals, can lead to PML.
Even so, the case will put Ocrevus under increased scrutiny. If Roche's drug is to eclipse Tysabri and to give Tecfidera a run for its money, it will need to maintain its strong safety profile.