JAK inhibitors are immune-modulating medications that target the JAK-STAT signaling pathway, which plays a key role in inflammatory diseases like atopic dermatitis. By blocking Janus kinase (JAK) enzymes, these drugs interfere with the transmission of inflammatory signals from immune cells, helping to calm the overactive immune system and reduce inflammation, itching, and eventually self-inflicted, skin lesions in pets.
Following the lead in Human Health where these JAK Inhibitors were already commercialized, Animal Health Industry witnessed the regulatory approval of 1st JAK-Inhibitor, with the launch of Apoquel® (oclacitinib maleate), way back in January 2014.
JAK-Inhibitors’ have a unique and innovative mode of action, as they target specific pathways of pruritus (itch) and inflammation, which makes them different from glucocorticoids, the existing mainstays on treatment. JAK-Inhibitors are also less likely to have unwanted side-effects and also act rapidly (demonstrating anti-pruritic efficacy within hours) to reduce the itch, unlike cyclosporine which can take up to a month to control pruritus.
Following a free-run for over a decade, Zoetis, the makers’ and marketeers of Apoquel – carried out extensive market outreach and established it as a standard of therapy in Atopic Dermatitis, with virtual 100% share of veterinary clinics and netting over USD 400 Million in annual revenues in 2024.
Entry of Competitors’
Super success of Apoquel in Pet Dermatology had to attract competition but unlike Human Pharma, competitors’ were relatively slow to get on JAK-Inhibitors’ bandwagon with the 2nd JAK-inhibitor, Zenrelia (ilunocitinib), getting US FDA Approval only in September of 2024 and EU Approval in July of 2025.
Thus over a decade long solo run for of Apoquel® (oclacitinib maleate) as the only JAK-Inhibitor approved for animal usage, came under some threat both at its home turf of US as well as in EU.
The unique proposition of Zenrelia (ilunocitinib), although still a non-specific JAK-Inhibitor, is that it minimizes the opportunity for rebound itch given its consistent once daily dosing compared to the market incumbent.
However, the initial adoption of Zenrelia (ilunocitinib) by Vets and its impact on Apoquel was limited on account of a ‘boxed warning it was asked to carry on the packs by FDA, which related to concurrent vaccine administration based on the results of a vaccine response study. That this boxed warning has now been done away with, has only raised the stakes for Zoetis
Numelvi from Merck / MSD – with compelling arguments
Much before Zenrelia could savor its success, Numelvi (atinvicitinib) from Merck / MSD received its approval from EU in the last week of July 2025.
Similar to the other 2 JAK-Inhibitors’ – while Numelvi (atinvicitinib) is also a once-daily, first-line treatment, but this is the only second-generation Janus kinase (JAK) inhibitor indicated for the treatment of pruritus associated with allergic dermatitis including atopic dermatitis and treatment of clinical manifestations of atopic dermatitis in dogs.
Second major factor in favor of Numelvi (atinvicitinib) is that it is at least 10-fold more selective for JAK1 than for JAK2, JAK3 and TYK2. JAK1 selectivity minimizes interference with the beneficial immune functions of the other JAKs, resulting in a compelling safety profile with proven efficacy in dogs and puppies. Thirdly It is the only JAK inhibitor approved for use in dogs as young as six months of age unlike the other 2 approved JAK-Inhibitors which are approved for usage from only 1 year of age.
So effectively not only Numelvi (atinvicitinib) has more bragging points but it also can further expand Atopic Dermatitis market by targeting Pets starting from 6 months of age, a huge positive over Apoquel and Zenrelia.
Impact on Zoetis
In a rare turn of fortunes for Zoetis shareholders, despite an 8% operational, organic growth in Q2’ 2025 revenues, coupled with 15% increase in Net Income and an impressive 18% increase in EPS per diluted share, Zoetis stock has remained sideways and at USD 148 as on 12th of September 2025, is perilously close to its 52-week low of USD 139.
Smart money is factoring in the expected stiff competition in Pet Derma from 2 new JAK-Inhibitors already on the market as well as heightened competition in US Market from Credelio Quattro, a first 4 APIs based endectocide available in US.
Comparative
| Apoquel – Zoetis | Zenrelia – Elanco | Numelvi – Merk / MSD | |
| Active | Oclacitinib | Ilunocitinib | Atinvicitinib |
| JAK-Inhibitor | 1st Generation | 1st Generation | 2nd Generation |
| Specificity | Non-Specific | Non-Specific | 10X more Specificity for JAK-1 Inhibitor |
| Age of Use | From 1 Year of Age | From 1 Year of Age | From 6 Months of Age |
| Approved in | World-wide | US and EU with increasing approvals in other countries | Only in EU at this moment |
| Brand Revenues | Over USD 400 Million | Under 50 Million | Getting Started |
Missing in Action
Whether the Pet Dermatology segment will witness the 4th JAK-Inhibitor – similar to 4 isoxazolines commercialized in parasiticides’ segment, from Boehringer Ingelheim, another Companion Animals Market Leader, remains to be seen as currently there is no public announcement by the organization of its interest in this particular segment. If and when BI gets in this segment, will only raise the stakes for incumbents in potentially 2nd highest grossing segment of Companion Animals, after the parasiticides segment led by Boehringer Ingelheim.
