Spotlight – following Humira in hidradenitis suppurativa
Immune agents old and new are trying to make a splash in what could turn into a billion-dollar market.
Data on three new therapies for the painful autoimmune disease hidradenitis suppurativa emerged last month, and one of these agents, UCB’s Bimzelx, will be heading to regulators later this year.
Many other projects are in development, including a round dozen in mid-stage trials. Important readouts due in the coming months include a data on a project from Moonlake Immunotherapeutics, for which expectations are particularly high. Here are the readouts to look out for.
On the cusp
Hidradenitis suppurativa is an autoinflammatory disease of the hair follicles, causing painful, recurring boils in areas of the body with sweat glands. Only around 1-4% of the US population is believed to have HS, and estimates of the current market size range from $600-900m – though Jefferies analysts write that in time, HS could be a multi-billion dollar market opportunity.
The only biological treatment currently available is Abbvie’s Humira and its biosimilars, and the disorder is a hotbed of pharmacological research. Some groups are seeking to redirect their successful autoimmune antibodies towards this disease, and others are developing entirely new agents. Novartis and UCB, the two most advanced companies here, are taking the former strategy.
Novartis disclosed last September that the pivotal HS trials of Cosentyx had succeeded, adding that the IL-17 inhibitor had been filed in the EU and US. The antibody is already approved for five autoimmune conditions including plaque psoriasis and psoriatic arthritis, so HS will be a relatively small market for Cosentyx.
UCB’s Bimzelx, which hits both IL-17A and IL-17F, was approved for psoriasis in 2021, though only, so far, in Europe. Its showing in the Be Heard I and II HS trials, presented at the American Academy of Dermatology’s annual meeting in March, was impressive – it looked better, on a cross-trial basis, than Cosentyx and roughly on a par with Humira.
Important data to come
Acelyrin’s izokibep also posted phase 3 data at the AAD conference, though this was only from the first, uncontrolled part of its trial. As such the data can be regarded as encouraging but not much more; results from the placebo-controlled part of the study will be more conclusive.
The only other potential HS therapy in phase 3 is Incyte’s Jak1 povorcitinib. In phase 2, patients given the agent for four months had significantly greater decreases in the number of abscesses and inflammatory nodules than those given placebo.
The twin phase 3 trials use a different measure as the primary goal: the proportion achieving HiSCR50, defined as a reduction of at least 50% in the total abscess and inflammatory nodule count, with no increase in abscess or draining tunnel count. This was also the measure used in the pivotal studies of Cosentyx and Bimzelx. Data are not expected for another couple of years.
|The late-stage hidradenitis suppurativa pipeline|
|Cosentyx||Novartis||IL-17 MAb||Hit in Sunshine and Sunrise trials; regulatory decisions due H1 2023 In EU, H2 2023 in US|
|Bimzelx||UCB||IL-17A & IL-17F MAb||Be Heard I and Be Heard II trials hit Mar 2023; filing planned for Q3|
|IL-17A antagonist||Part A of Ph2b/3 trial hit Mar 2023; part B data could come 2023. Second Ph3 trial planned.|
|Povorcitinib||Incyte||Jak1 inhibitor||Stop-HS1 and Stop-HS2, each in 600pts, could report 2025|
|All trials in moderate to severe disease. Source: Evaluate Pharma, clinicaltrials.gov.|
The list of HS projects in phase 2 trials is more mechanistically diverse than the late-stage pipeline, though IL-17s and Jaks are also present.
Data was presented at AAD from the phase 2 trial of Lilly’s eltrekibart (LY3041658). Here HiSCR50 was achieved by 66% of patients given the CXCR1 & CXCR2 inhibitor for four months, versus 41% of placebo-treated patients. The delta of 25 points means eltrekibart looks competitive with Bimzelx, though of course this will have to be borne out in phase 3. Lilly has not made its plans here clear.
Abbvie is slightly behind with Rinvoq. In a phase 2 trial, 38% of patients given the Jak1 for three months hit HiSCR50, compared with 25% of placebo patients. The difference was statistically significant at p=0.018, but the difference of 13 points might not be enough to convince dermatologists – or payers. Abbvie has not announced any plans for phase 3.
One of the brightest hopes among the mid-stage players is Moonlake Immunotherapeutics, whose nanobody sonelokimab has a similar mechanism to Bimzelx. It is in fact trispecific, targeting both IL-17A and IL-17F as well as albumin; this mechanism ought to allow it to easily penetrate the skin, SVB analysts believe.
The phase 2 trial tests two dose levels of sonelokimab versus both placebo and Humira, with the endpoint being HiSCR75; HiSCR50 is a secondary measure. Analysts from several banks regard the phase 3 showing of the similarly-acting Bimzelx as derisking Moonlake’s readout, and Moonlake’s shares have climbed 20% in the past month, largely as a result of UCB’s success.
SVB analysts write that sonelokimab’s shorter half-life compared with Bimzelx could result in lower rates of candidiasis and improved tolerability. They raised their probability of success for the project from 45% to 60% in the wake of the Be Heard data.
Jefferies analysts write that when sonelokimab’s phase 2 trial reports mid-year, a cross-trial 10-15% improvement over Bimzelx on HiSCR50 or 75 would be seen as superior efficacy.
|The mid-stage hidradenitis suppurativa pipeline|
|LY3041658||Eli Lilly||CXCR1 & CXCR2 MAb||Ph2 trial hit Mar 2023|
|Spevigo||Boehringer Ingelheim||IL-36 MAb||Ph2 trial in 45 pts hit Mar 2022; extension trial could report 2024|
|Rinvoq||Abbvie||Jak1 inhibitor||Ph2 trial hit Feb 2023|
|Sonelokimab||Moonlake Immunotherapeutics||IL-17A & IL-17F MAb||Ph2 trial in 210 pts could report topline data mid-2023|
|BDB-001||Staidson Beijing Biopharmaceuticals||Complement factor C5a MAb||Ph 1/2 trial in 49 pts has completion date of Dec 2022 but marked as recruiting; Ph2 trial in 49 pts could report 2023|
|Iscalimab (CFZ533)||Novartis||CD40 antibody||Ph2 trial in 200 pts could report 2023|
|Remibrutinib (LOU064)||BTK inhibitor|
|Lutikizumab||AbbVie||IL-1A & IL-1B MAb||Ph2 trial in 160 pts who have failed on anti-TNFs could report 2023-4|
|Opzelura||Incyte||Jak1 & Jak2 inhibitor||Ph2 trial in 60 pts w disease of any severity could report 2024; Ph2 trial in 24 pts w early-stage disease could report 2024-5|
|Orismilast Oral||Leo Pharma/Innovent Biologics/
|PDE4 inhibitor||Ph2 Osiris trial in 24 pts w disease of any severity has completion date of Dec 2022 but marked as not yet recruiting|
|Zunsemetinib||Aclaris Therapeutics||MAPK2 inhibitor||Ph2a trial failed Mar 2023|
|RIST4721||Aristea Therapeutics||CXCR2 antagonist||Discontinued Feb 2023 following safety findings in Ph2 trial; company dissolved|
|Bermekimab||Johnson & Johnson||IL-1A MAb||Ph2 Lyra trial terminated for futility Nov 2022|
|All trials in moderate to severe disease unless stated. Source: Evaluate Pharma, clinicaltrials.gov.|
Boehringer Ingelheim also had data at AAD. In a phase 2 trial patients given the IL-36 MAb Spevigo for 12 weeks had a 39% reduction in HiSCR, versus 35% of placebo-treated patients. The researchers said that overall, these results support the agent's development in HS.
Beyond phase 2 there is some interest in Irak4 degradation as a mechanism here, with Kymera Therapeutics aiming to put its KT-474 in phase 2 trials in HS this year. Last week Gilead licensed Nurix’s Irak4 degrader NX‑0479, and while it has not said that it will try this in HS, that remains a possibility.
Mechanistically, however, the IL-17s look like the ones to beat.