Event – Abbvie’s long shot at proving Rova-T doubters wrong

When it comes to making overpriced acquisitions Abbvie has a bit of a history. It could redeem itself in the second half of this year with the readout of a registrational trial of Rova-T, an asset it got through the $5.8bn buyout of Stemcentrx.

On the other hand, early survival data with Rova-T in small-cell lung cancer have underwhelmed, calling into question the logic of Abbvie’s Stemcentrx move. Trinity, the registrational trial due to read out shortly, tests the project in the same indication, and sellside consensus suggests that Abbvie faces a tall order.

Third-line small cell lung cancer (SCLC), studied in Trinity, looks to be the first indication Abbvie targets with Rova-T, in spite of the previous mixed data in this disease. On its fourth-quarter call the group spelled out that Trinity, though formally designated phase II, would serve as the basis for a submission shortly after data readout, leading to first launch in 2018.

Project Rova-T
Company Abbvie
2022e sales $1.2bn
Product NPV $7.1bn
% of market cap 6%
Event Data from Trinity study in 3L SCLC
Date H2 2017

Rova-T is an antibody-drug conjugate that targets DLL3, an atypical Notch ligand said to be overexpressed in over 80% of SCLC and large cell neuroendocrine tumours.

The project’s NPV of $7.1bn, as calculated from EvaluatePharma’s sellside consensus numbers, is above the $5.8bn in cash and stock that Abbvie had paid for Stemcentrx up front, but well short of the $9.8bn the deal is worth if future earnouts – which would presumably be triggered in the event of successful development – are included.

In February Evercore ISI wrote that Rova-T data were crucial for Abbvie’s numbers and sentiment alike. On a 100% probability basis Rova-T’s NPV rises to a huge $22.9bn, with sales peaking above $2bn before patent expiry in 2031, showing how much Abbvie needs Rova-T to work to justify its outlay.

Tall order?

Judging by data presented at Asco in 2016 this could be tricky. Progression-free survival in a first-in-human trial in various SCLC settings was 2.8 months, compared with the three months or more typically seen with topotecan, the only FDA-approved drug for recurrent SCLC (Asco 2016 – AbbVie pulls back rova-T curtain, June 6, 2016).

Data did show an 18% overall remission rate, and at least the fact that responses were driven by activity in DLL3 expressers – subjects showing the antigen on 50% or more of their cells had 39% overall remission – backed up Rova-T’s mechanistic rationale.

Still, Trinity has recruited a broader patient group – those expressing DLL3 at just 1% or above – so this benefit might not feed through as clearly.

The single-arm Trinity trial has recruited 339 patients with third or later-line SCLC, and measures objective response and overall survival as co-primary endpoints. Also favouring it was the subgroup finding at Asco that remission rate was stronger in third rather than second-line patients, at 50% versus 29% respectively.

A separate Rova-T study, in neuroendocrine tumours, could yield early data this year. Meanwhile, two phase III trials, Maru and Tahoe, are under way in settings that will be key to expanding Rova-T’s potential beyond the relatively narrow use of late-line SCLC.

Abbive has also made much of the pipeline Stemcentrx has given it, and this now comprises four clinical assets, with several additional projects to enter trials this year.

However, as far as proving the value of Stemcentrx Abbvie still has it all to do. Beyond its most important task – defending Humira patents – the company has yet to demonstrate that it is capable of doing wise acquisitions.

Study Detail Trial ID
Trinity 3L and later SCLC expressing DLL3 >1% NCT02674568
Meru SCLC maintenance after 1L Pt chemo NCT03033511
Tahoe High-DLL3 and chemo-progressed SCLC  NCT03061812

To contact the writer of this story email Jacob Plieth in London at jacobp@epvantage.com or follow @JacobPlieth on Twitter

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