Mirikizumab would, if launched in late 2021, be a late entrant to the crowded psoriasis market. This perhaps explains why Lilly is simultaneously pushing ahead with phase III trials of the anti-IL-23 MAb in ulcerative colitis and Crohn’s disease.
This clinical programme is phenomenally expensive for a project that is still somewhat under the radar. EvaluatePharma Vision's R&D cost model* estimates that the total clinical development of mirikizumab will cost Lilly $1.4bn, including almost $300m this year. This is not an insignificant investment for what will become the third IL-23 to market in psoriasis – suggesting that the GI disorders might be where Lilly sees the real opportunity.
|% of market cap||3%|
|Event type||Phase III trial results|
Still, the psoriasis market should not be overlooked, and upcoming data from a phase III trial should give a sense of how well mirikizumab might do against the competition. The Oasis-2 study is expected to report this spring, and has enrolled nearly 1,500 patients with moderate to severe plaque psoriasis. It is pitting mirikizumab against Novartis’s Cosentyx, and as such is the first phase III study in any of the project’s indications evaluating it against an active control.
The primary endpoints, both assessed after four months of treatment, are the percentage of patients with a two-point improvement from baseline on the static physician’s global assessment (PGA), and the proportion achieving PASI 90 – a 90% improvement from baseline on the psoriasis area and severity index.
Cosentyx, an anti-IL-17A, is forecast to become the psoriasis market leader by 2024 according to EvaluatePharma’s sellside consensus. But Abbvie’s Skyrizi is really the one to beat here: the IL-23 antibodies have significantly improved treatment outcomes in the skin disease, and for now Skyrizi is viewed as the most effective.
|Comparison of phase III data on selected IL-23s and IL-17s in psoriasis|
|Company||Johnson & Johnson||Abbvie||Johnson & Johnson||Novartis|
|Therapy||Stelara (IL-12/IL-23)||Skyrizi (IL-23)||Tremfya (IL-23)||Cosentyx (IL-17)|
|Trial||Phoenix 1||Phoenix 2||Ultimma-1||Ultimma-2||Voyage-1||Voyage-2||Erasure||Fixture|
|PAI in PGA of clear or almost clear (%)||57||69||80||79||78||76||63||59|
|PAI in Pasi 75 (%)||63||72||78||71|
|PAI in Pasi 90 (%)||70||73||70||68|
|PAI = placebo-adjusted improvement. PGA = physician’s global assessment. Source: drug labels.|
PASI 90 is of course a tougher bar to hit than the PASI 75 at which mirikizumab is aiming in Oasis-2. The Oasis-1 study, which completed last year, uses PASI 90 as its co-primary – but Lilly is yet to report the data from this trial. At time of writing, the company has not responded to enquiries regarding the release of the Oasis-1 data.
Another piece of the puzzle is the revelation three weeks ago that Skyrizi trounced Cosentyx in a head-to-head phase III trial. Abbvie’s MAb scored a PASI 90 rate at four months of 74%, compared with 66% for Cosentyx. At one year the other primary endpoint, the PASI 90 difference, was starker: 87% for Skyrizi versus 57% for Cosentyx. Skyrizi also showed superiority over Cosentyx for all the trial’s secondary endpoints, including PASI 100, PASI 75, and PGA of clear or almost clear.
Current consensus forecasts for mirikizumab peg its 2024 sales at $759m; this would make it the ninth-biggest psoriasis seller that year. Lilly’s own blockbuster, the anti-IL-17 Taltz, is number seven.
A bigger opportunity?
Developers hope that the IL-23 agents also hold big potential in autoimmune bowel disorders, and major clinical programmes are under way here. The first of mirikizumab’s phase III trials in ulcerative colitis, Lucent-1, yields data towards the end of this year. This is far ahead of Tremfya, whose Quasar phase II/III UC study will not report until late 2022.
Skyrizi, however, could be a threat: a phase II/III study of Abbvie's product is due to conclude in September – neck and neck with Lucent-1. This will be followed by a phase III that could yield data on Skyrizi in 2022 or 2023, again suggesting a similar timeline to mirikizumab.
Stelara, which hits IL-12 as well as IL-23, was approved for the condition last October on the back of a 19% clinical remission rate in the Unifi trial. There are hopes that pure IL-23s will be best-in-class here, as they have proved in psoriasis. Lucent-1 and the Skyrizi trial will be the first big tests of this hypothesis.
For mirikizumab, the focus remains on psoriasis for now – but this market is home to six blockbusters already, so Lilly must be hoping for more. With no timing advantage over Skyrizi, its challenges in ulcerative colitis are not inconsiderable either.
|Mirikizumab’s phase III programme|
|Oasis-1||Psoriasis||Vs placebo||530||Completed||Mar 2019|
|Oasis-2||Psoriasis||Vs Cosentyx and placebo||1,443||Active||Mar 2020|
|Lucent-1||Ulcerative colitis||Vs placebo||1,160||Recruiting||Sep 2020|
|Lucent-2||Ulcerative colitis||Vs placebo||1,044||Recruiting||Jun 2021|
|Lucent-3||Ulcerative colitis||840||Recruiting||Aug 2023|
|Vivid-1||Crohn's disease||Vs Stelara and placebo||1,100||Recruiting||Feb 2022|
|Vivid-2||Crohn's disease||778||Not yet recruiting||Nov 2023|
|Source: EvaluatePharma, clinicaltrials.gov.|
*EvaluatePharma Vision’s R&D cost model estimates the cost of individual clinical programmes using real-world data. Company disclosed product-level spend and clinical trial patient numbers are combined to create cost per patient benchmarks by technology and therapy type. Utilising a matching algorithm, these benchmarks are applied to all commercially relevant clinical trials to estimate their cost, which can then be aggregated by product to estimate the cost of development of all products.