The autoimmune market has become an increasingly hot target in pharma. With 80-plus debilitating and sometimes deadly autoimmune diseases in need of better treatments, the global market, which rang in at $109 billion in 2017, is expected to rise to more than $153 billion by 2025.
“What we will hopefully see, and are poised to see over the next 15 years, is a transformation in autoimmune disease therapy in the same way that we’ve seen for oncology in the last 10 to 15 years,” says Ben Zimmer, CEO of Priovant Therapeutics. “I think that there’s a lot of increased recognition of the severity of many of these diseases and the burden on patients.”
Priovant, a clinical-stage biotech created through a partnership between Pfizer and Roivant Sciences, is positioning itself at the forefront of this burgeoning market with its dual JAK1/TYK2 inhibitor drug, brepocitinib. Pfizer conferred the rights to oral and topical brepocitinib to Priovant, but retained 25% equity ownership interest in the company.
“Roivant contributed capital and several of the initial team came over from Roivant, including myself,” Zimmer says.
Since its formation in Sept. 2021, Priovant team members, which now number around 40 people, have been building the organization and solidifying its approach.
“We’re really homing in on our development strategy with the asset, a drug that I think you can take in a lot of directions,” Zimmer says.
Brepocitinib is unique because it inhibits not one, but two enzymes, TYK2 and JAK1, which play a role in autoimmune disease, Zimmer says. It’s currently the only dual inhibitor in late-stage development — and could potentially be the first to hit the market, filling crucial treatment gaps.
So far, the drug has shown promise in treating multiple autoimmune diseases. But the company, which also has a selective TYK2 inhibitor, is primarily focusing on indications for brepocitinib in areas with high unmet need and high morbidity and mortality, instead of initially aiming for more competitive big-game targets, such as psoriasis.
The lead indications for brepocitinib are two serious autoimmune conditions — systemic lupus erythematosus and dermatomyositis. Lupus affects the skin, joints and some organs, while dermatomyositis is a rare disease that affects the muscles and skin. Both conditions are highly inflammatory, and complex — and current treatment options are limited and often inadequate. The company hopes to fill that void.
All phase 2 studies of oral brepocitinib to date have shown “statistically significant and clinically meaningful efficacy results,” according to Priovant.
But like many other autoimmune treatments, the drug does have some drawbacks. Its safety profile is similar to approved JAK inhibitors, such as Xeljanz, which were recently flagged with a warning by the FDA due to their link to a higher risk of serious heart-related events, such as blood clots, heart attack, stroke and death. Still, for some patients with serious conditions and few treatment options, the benefits may outweigh the risks.
“Years of experience using JAK inhibitors in patients with dermatomyositis has shown us that these agents can profoundly benefit patients with uncontrolled disease,” Dr. Ruth Ann Vleugels, a principal investigator for the Priovant study of brepocitinib in dermatomyositis, and the Heidi and Scott C. Schuster distinguished chair in dermatology at Brigham and Women’s Hospital and director of the Autoimmune Skin Diseases Program and Connective Tissue Disease Clinics, says. “Given the devastating manifestations of dermatomyositis and its substantial impact on quality of life, the benefits of treatment with JAK inhibitors outweigh the potential risks in the vast majority of patients in our clinic.”
Here, Zimmer discusses Priovant’s mission and the potential path ahead for brepocitinib.
PharmaVoice: Why did the company decide to make systemic lupus erythematosus (SLE) and dermatotmyositis its lead targets?
Ben Zimmer: I would say it's really three criteria. First, is very high morbidity and mortality. Both lupus and or dermatomyositis involve very debilitating symptoms and have a five-year mortality rate over 10%. In dermatomyositis, [mortality has] been estimated from 10% of all the way up to 40%. So, these are very serious conditions.
Second, is there's very little available by way of treatments. For dermatomyositis, it's really just steroids, general immunosuppressants, and intravenous immunoglobulin, which involves a very burdensome administration. You have to go in for an infusion once a month and you have to do it for two to five days, for several hours. There are also significant side effects associated with it. In lupus, there are two targeted biologics approved, but there are large numbers of patients who are either unresponsive to them or who experience some benefit but continue to have bad symptoms on certain organ domains.
And then the third is that we think these are diseases uniquely well suited to the novel mechanism of dual inhibition of TYK2 and JAK1. We think that a drug that inhibits both of those will be more efficacious than one that inhibits just one or the other. And that's because different cytokines that are mediated through both TYK2 and JAK1are implicated in the pathology of the diseases.
Are you working on the other applications for brepocitinib?
Zimmer: Yes. One is a for a disease called noninfectious uveitis, which is an ocular disease that again, has very severe, symptoms. Large numbers of patients end up going blind from it and again, there is very little available [to treat it]. So, we're initiating a phase 2 proof-of-concept study later this year.
Another indication of potential interest for us is Hidradenitis [Suppurativa, a chronic inflammatory skin condition]. We actually got positive phase 2 data earlier this year and are considering next steps now. We haven't finalized our plans yet but are thinking that through. And then I think there are a variety of other autoimmune diseases as well where we may bring the drug forward and are exploring it.
What have you been most excited about in your trial results so far?
I think what you see is very robust, statistically significant, clinically meaningful efficacy across a wide variety of different indications. So, you have certain indications, like plaque psoriasis, or Hidradenitis Suppurativa, where you see very strong benefit on skin-predominant indications. In ulcerative colitis, it’s been efficacious in the GI-focused indication. In psoriatic arthritis, you see a lot of benefit on joints. So, I think, what you see is that this is a drug that appears to be highly efficacious. We need to confirm this through our investigational programs, but all evidence to date suggests, in a robust way, that it works. I don’t think that's something to be taken for granted in biopharma. So then the question is, where, with a drug that appears to be so potentially efficacious, can we generate the greatest impact for patients?
What would be the timeline where you think you might be able to get approval for dermatomyositis and lupus?
We're in phase 3 for dermatomyositis (DM) and then for lupus, we're in phase 2. But the [phase 2 lupus] study is designed to serve as a one of two registrational studies. So, our hope and belief is that if that study generates very good data, we would just do one confirmatory phase three study in lupus.
For DM, we expect to have data most likely in the second half of 2025. Depending on how things unfold, we could potentially have approval by the end of 2026. In lupus, we'll be reading out this study in the second half of next year, of 2023. If that data looks good, we would immediately on the back of that initiate our second registrational program and so could expect to have approval, probably after dermatomyositis, but not too far behind.