Troubled Zinbryta might not be missed in stagnant multiple sclerosis space

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The only surprising thing about Zinbryta’s exit from global multiple sclerosis markets is how little it seems to matter.

Biogen and Abbvie’s decision to withdraw comes in the context of an MS arena that has stagnated, with Roche’s late entrant Ocrevus and Sanofi’s Lemtrada the only marketed products in the top 10 set to show steady growth through 2022 (see table). As Biogen is heavily exposed to wobbles in the MS market, having four drugs on sale in this space, it is little wonder that the Massachusetts-based group is seeking to diversify into Alzheimer’s disease and ophthalmology.

MS drugmakers have suffered from a combination of ageing products, increasing competition and pricing scrutiny. Copaxone’s loss of patent protection has been devastating for Teva, and the interferons are either nearing the end of their market exclusivity or have already lost it, although serious biosimilar competition has emerged only in Russia so far.

Price rises entered into the US political debate last year, possibly stopping bigger hikes by the likes of Biogen, Merck KGaA, Bayer, Novartis and other groups active in this area (Spotlight – Multiple sclerosis drugs not alone with double-digit price hikes, September 5, 2017).

Top 10 agents in multiple sclerosis
Annual MS sales ($m)
Product Company 2016 2018 2020 2022 Annual growth rate
Ocrevus Roche - 2,080 4,055 5,111 n/a
Tecfidera Biogen 3,968 4,252 4,059 3,818 -1%
Aubagio Sanofi 1,433 2,164 2,304 1,781 4%
Gilenya Novartis 3,109 3,330 2,138 1,349 -13%
Tysabri Biogen 1,964 1,717 1,438 1,303 -7%
Avonex Biogen 2,314 1,941 1,586 1,244 -10%
Rebif Merck KGaA 1,926 1,803 1,485 1,181 -8%
BAF312 Novartis - - 437 1,103 n/a
Lemtrada Sanofi 470 665 737 794 9%
Ozanimod* Celgene - 19 524 745 n/a
Other 6,666 4,503 3,673 3,998 -8%
Total 21,850 22,474 22,437 22,428 0%
*Forecasts likely to be downgraded. Source: EvaluatePharma.

New products BAF312 and ozanimod cannot be relied on to drive much growth. Both are S1P 1 & 5 modulators, and Novartis’s BAF312 will probably cannibalise sales of Gilenya, an S1P antagonist that loses patent protection in 2019. Celgene’s ozanimod last week suffered the indignity of a refusal-to-file letter from the FDA that could set back approval by a year.

And Santhera's announcement today that Raxone had failed in an MS trial should not create any optimism that innovation will lead to steady growth in the near future.

Pressure

Zinbryta had been under increasing pressure as regulators became concerned about liver-related side effects, and necessary monitoring was likely a turn-off for many patients.

European action that restricted its use to patients who had progressed on two other disease-modifying therapies forced Biogen to take a $42m charge last year, and a further investigation into reports of inflammatory encephalitis and meningoencephalitis would not have done the product any favours.

In a statement Biogen and Abbvie said they would not be able to show Zinbryta’s risk-benefit profile “given the limited number of patients being treated”.

Patient numbers were limited indeed. Sales in 2017 were $147m, and the US Medicaid programme for low-income and disabled people reported that just 181 Zinbryta prescriptions were written for beneficiaries in the third quarter of 2017. The outlook for the anti-IL-2 antibody has been downgraded massively since it completed clinical trials more than two years ago.

Moreover, in an analysis of clinical data prepared for the Institute for Clinical and Economic Review by an advisory panel of the California Technology Assessment Forum, Zinbryta was judged to be no more effective than the oral drugs Tecfidera or Gilenya; the same panel was split over whether it was more effective than generic versions of Copaxone, an injection.

Given Zinbryta’s dimming prospects and the state of the MS space, it was probably not a difficult decision to cease marketing. Biogen’s efforts to innovate here have been less than successful since it brought Tecfidera to the market in 2013. Perhaps the group should consider exiting what is looking to be a less lucrative MS market.

To contact the writer of this story email Jonathan Gardner in Virginia at jonathang-us@epvantage.com or follow @ByJonGardner on Twitter

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