Asco propels PD-1s into most valuable asset rankings

Cancer immunotherapies stole the show at Asco despite their data being from early trials, and the resulting sellside upgrades have given these projects prominent billing in the industry’s ranking of the most valuable development-stage assets.

Bristol-Myers Squibb’s nivolumab now stands as the most valuable phase III project with an NPV of $11.5bn, the latest analysis based on EvaluatePharma consensus data shows, Elsewhere, the advance of Gilead Science’s sofosbuvir makes this the top filed asset, with a massive $26.6bn of NPV. But the ranking also holds surprises, featuring several projects that still have questions to answer.

Many of the newcomers to the latest ranking have come courtesy of top spots being vacated by launches of big drugs, including Biogen Idec’s Tecfidera, Pfizer’s Xeljanz, Roche’s Kadcyla and Bayer’s Xofigo.

Some care should be taken with analysing the expected hepatitis C blockbuster sofosbuvir given that its combination with ledipasvir also features separately in phase III this year – not all analysts split out the sales, and some of sofo’s $26.6bn might relate to the combo.

But none of this alters the fact that sofo is expected to become a very big drug indeed. It topped the ranking of phase III assets last year, too (Biogen and Gilead top tables with most valuable R&D assets, August 8, 2012).

Zero to hero

More unexpected is the entry into the ranking of Lilly’s ramucirumab and Celgene’s apremilast. The former had barely registered on analysts’ radars until gastric cancer data were announced last October from a phase III trial that until then had been deemed merely “supportive”, while the latter faces some doubts over the size of the psoriatic arthritis market.

Top 10 filed projects by NPV
Project Company Pharmacology class Today's NPV ($m) Filed indication
Sofosbuvir Gilead Sciences Nucleoside NS5B polymerase inhibitor 26,554 Hepatitis C
Ramucirumab Eli Lilly Anti-VEGFr MAb 4,277 Stomach cancer
Anoro Ellipta GlaxoSmithKline LAMA & LABA 2,574 COPD
Macitentan Actelion Endothelin receptor antagonist 2,410 Pulmonary hypertension
Dolutegravir GlaxoSmithKline HIV integrase inhibitor 2,400 HIV
Apremilast Celgene PDE4 inhibitor 2,045 Psoriatic arthritis
Riociguat Bayer Guanylate cyclase activator 1,971 Pulmonary hypertension
Vortioxetine Lundbeck 5-HT3 & 5-HT7 antagonist, 5-HT1B partial & 5-HT1A agonist, 5-HT re-uptake inhibitor 1,867 Depression
Obinutuzumab Roche Anti-CD20 MAb 1,520 CLL
Vonicog alfa Baxter International Von Willebrand factor 1,390 Von Willebrand disease

Recent approval of GlaxoSmithKline/Theravance’s Breo Relvar bodes well for the chances of the groups’ entirely novel LABA/LAMA combination Anoro Ellipta – worth $2.6bn to Glaxo. The list of the top filed assets includes both macitentan and riociguat, presaging what should be a fierce battle between the two in pulmonary hypertension (Riociguat trial success puts pressure on macitentan, October 22, 2012).

Of course, the major stock price-moving event of recent months was Asco, and it is courtesy of this that Roche’s obinutuzumab and Bristol and Merck & Co’s respective anti-PD-1 antobodies, nivolumab and lambrolizumab, come in as new entries (Asco Event Analyzer – 2013’s winners and losers, June 6, 2013).

Roche had surprised with strong phase III data in elderly chronic lymphocytic leukaemia patients. For the other two it was a case of phase I melanoma data being perceived as highly positive and boding well for phase III and perhaps fast approval (Roche’s heir to the Rituxan throne ensures succession with regicidal data, July 24, 2013).

Top 10 phase III projects by NPV
Project Company Pharmacology class Today's NPV ($m) Phase III indication(s)
Nivolumab Bristol-Myers Squibb Anti-PD-1 MAb 11,472 Melanoma, NSCLC, renal cell carcinoma
Afrezza Mannkind Insulin 7,506 Diabetes
Ledipasvir plus sofosbuvir (GS-7977/GS-5885) Gilead Sciences Nucleoside NS5A & NS5B polymerase inhibitor 6,921 Hepatitis C
Palbociclib Pfizer CDK 4 & 6 inhibitor 4,660 Breast cancer
Ibrutinib Pharmacyclics Bruton's tyrosine kinase inhibitor 4,083 CLL, non-Hodgkin's lymphoma
Lambrolizumab Merck & Co Anti-PD-1 MAb 3,932 Melanoma
Reolysin Oncolytics Biotech Oncolytic virus - Ras activated 3,929 Head & neck cancer
Ivacaftor plus lumacaftor Vertex Pharmaceuticals CFTR corrector 3,574 Cystic fibrosis
Onartuzumab Roche Anti-c-Met MAb 3,439 NSCLC, stomach cancer
Solanezumab Eli Lilly Anti-beta amyloid Mab 3,144 Alzheimer's disease

Meanwhile, with Kalydeco marking Vertex’s transition from a hep C to a cystic fibrosis player, all eyes are on follow-on combinations boasting synergistic activity that could expand the group’s market share. Kalydeco’s combo with lumacaftor carries an NPV of $3.6bn, with launch expected in 2015 and sales of $1.4bn by 2018.

Surprises

And there the surprises really begin – none more bizarre than the entry of Mannkind’s phase III inhaled insulin Afrezza at number two. Most of its $7.5bn of NPV is dependent on partner sales – no deal has materialised yet – and investors will soon find out whether phase III readout validates their chief executive’s blind faith or if the company’s struggle against adversity will continue (Event – Mannkind's soap opera nears another crossroads, July 5, 2013).

Meanwhile, Oncolytics Biotech’s oncolytic virus project Reolysin carries a massive burden of expectation, despite its confusingly designed phase III study – in fact this is no longer deemed pivotal. The serious doubts that Amgen’s rival T-Vec recently cast about the practicalities of using oncolytic viruses therapeutically does not help its case.

And the beta amyloid antibody solanezumab makes it into the ranking thanks to Lilly’s dogged determination to persist with a new phase III trial next year on the strength of borderline positive signals in two failed pivotal studies. A year ago – before these failures had read out – the project did not even feature in the top 10.

Much of this exuberance is of course the result of the sellside trying to keep ahead of an increasingly frothy biotech market. While many of the industry’s top assets are consolidating their positions, some of the newcomers still have much to prove.

To contact the writer of this story email Jacob Plieth in London at [email protected] or follow @JacobEPVantage on Twitter

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