Biogen’s aducanumab shoulders sector’s pipeline hopes, again

It seems unbelievable that, after more setbacks in Alzheimer’s disease this year, Biogen’s aducanumab still tops the chart of biopharma’s biggest pipeline prospects. And hopes for the project have risen in the past 12 months despite little new evidence supporting the seemingly bulletproof amyloid hypothesis.

Aducanumab would be worth much more than currently forecast if it does succeed, but this is unlikely given the lamentable track record of amyloid-targeting Alzheimer’s agents. An analysis of sellside forecasts reveals that the Biogen project is not the only one carrying huge expectations; valuations for some of the other big pipeline hopes could also be hard to achieve.

The above analysis, of projects being developed by large biopharma companies, is based on EvaluatePharma’s NPVs of a consensus of sellside forecasts. 

It is not only aducanumab that looks to have a stretched valuation. Celgene’s JCAR017, gained through the purchase of Juno, would be the third CD19-targeting CAR-T therapy to market, after Novartis’s Kymriah and Gilead’s Yescarta, yet its NPV is on a par with the latter, and double the former. 

One group hoping to burst the CAR-T bubble is Glaxosmithkline, which believes that its anti-BCMA antibody-drug conjugate, GSK2857916, could provide a cheaper and more convenient alternative to cell therapy in multiple myeloma.

The company has hardly been an oncology stalwart in recent years, but recent efforts to talk up its cancer pipeline have clearly paid off, as its anti-Ox40 MAb also makes an appearance. Remarkably, the asset is still in phase I. Added to doubts about Ox40 as a target, this project looks like a very long shot.

The price is right?

Oncology and rare diseases, areas where companies are still able to charge top dollar, are both well represented in this analysis. Still, pressure is growing to price responsibly in all areas, and this could affect several of the projects listed above.

Vertex, for example, will have to tread carefully with its cystic fibrosis franchise. As well as VX-659/tezacaftor/ivacaftorone it has another triplet in phase III, and hopes to expand the proportion of patients eligible for therapy, but it is already coming under fire for the cost of its existing CF drugs.

Meanwhile, estimates for Shire’s big pipeline hope, lanadelumab, are looking rich ahead of an approval decision later this month – with other hereditary angioedema products already available, the company’s pricing strategy will be key to its success.

Haemophilia A is another rare disease dominated by pricey therapies, this time factor replacement products, and there are hopes that gene therapies could disrupt the market. Two candidates, Biomarin’s valoctocogene roxaparvovec and Spark’s 8011, are on the roll call of the sellside’s most valuable assets, with the latter featuring in an earlier analysis of unpartnered projects owned by smaller drug makers (Most valuable unpartnered assets reveal a changing of the guard, August 14, 2018).

There are even higher expectations for the spinal muscular atrophy gene therapy contender, AVXS-101 – one of the most-hyped unpartnered prospects a year ago, which has since been picked up by Novartis.

The Swiss company now has the task of not only getting the project approved but also justifying the $8.7bn it paid for AVXS-101’s developer, Avexis. After the commercial disappointment of Kymriah, another lacklustre launch could raise questions about Novartis’s push into cutting-edge technologies.

Still, worries about launches and pricing would be irrelevant in the light of a clinical failure – and with most of the above projects in phase III, this is still a real risk. Abbvie’s Rova-T and Roche’s lampalizumab both featured in last year’s analysis of the most valuable pipeline assets, but have since flopped in clinical trials – although most of the projects on last year's list made it through to approval (Biogen’s Alzheimer’s hope tops the sector’s most valuable pipeline prospects, 16 August 2017).

History suggests that aducanumab will end up going the same way. But the potential rewards so high, expectations for the project could creep up again ahead of phase III results, which are not due until 2020.