There is only one approved treatment for hidradenitis suppurativa (HS), despite millions suffering from this horrible condition involving keloids, contractures, and immobility, not to mention extremely painful inflammatory nodules, boils, and abscesses often occurring in the armpit, groin, and genital areas. Although targeted numbers may vary based on various data points, TrialSite News suspects this is an under-diagnosed disease afflicting over 3 million people. There are many HS patients in the TrialSite Network, which sponsored a podcast highlighting an HS patient story. Many suffer in silence as the condition hasn’t received the attention it deserves. The condition appears to be more common in women, those aged 18-49, African Americans, and possibly those that may also struggle with weight and other comorbidity-related issues—but this potentially debilitating condition can occur across many demographic segments. TrialSite News knows of a handful of affluent corporate executives that face the risk of career due to the debilitating impact of this insidious condition. HS patients can face severe conditions that inhibit a normal and healthy quality of life and can lead to severe pain-related conditions and even disability. To date, treatment is limited and consists mainly of antibiotic administration and a novel biological drug (Humira) with up to 40% efficacy; however, reports of severe side effects are frequent. It is good news that more research efforts are underway to better understand the condition and investigate new possible therapies to improve the quality of life for those afflicted with the disease. Joslyn Kirby, MD, a dermatologist with Penn State Health Milton S. Hershey Medical Center, reported a growing number of clinical trials addressing the condition last fall. TrialSite News updates the network with a sampling of HS clinical trials pipeline with links to some of the most prominent HS-focused key opinion leaders (KOLs) in the United States and beyond.
Presently, the only approved treatment for HS is adalimumab (Humira, AbbVie) reports, Dr. Kirby, a well-known and respected expert in the topic of HS, in Dermatology Times. Dr. Kirby reports, “We’re learning a vast amount about what’s happening in the skin with patients who have HS.” Highlighting this growing body of knowledge, Dr. Kirby emphasized, “We’re looking at all the different cell types and cytokines that play an even greater role so we can modify these contributions to the pain, drainage and the incapacity of hidradenitis suppurativa. We’re hoping for even greater patient outcomes.”
Unfortunately, Humira doesn’t work with everyone, and in fact, some reports lead to the conclusion that 60% of these patients aren’t served by the powerful immunosuppressive made by AbbVie—it’s top-selling drug. Hence, it is good news that research and development efforts, whether via industry sponsors or academic medical centers, are on the increase by 50% between 2017 and 2019 with a number of efforts focusing on interleukin-17 and interleukin-23 inhibitors.
Dr. Kirby is a champion of HS patient participants in biologic-focused clinical trials with a big caveat—that the right clinical trial must be paired with the appropriate HS patient, and she concedes this could be a pairing.
TrialSite News offers a breakdown of some ongoing or planned clinical trials. The focus is on new and novel approaches that may help patients deal with this challenging and potentially debilitating condition. We start with a study plan that Dr. Kirby just happens to be leading.
Penn State hypothesis: is ruxolitinib 1.5% cream an effective therapy for HS patients through inhibition or inflammatory activity?
As mentioned above, Penn State’s Milton S. Hershey Medical Center plans a clinical trial hypothesizing that ruxolitinib 1.5% cream is an effective therapy for HS patients, whether through inhibition or inflammatory activity. Starting in October 2020, 24 participants will be enrolled in this two-year Phase 2 study. Known as Jakafi and Jakavi, the Novartis therapy is used for the treatment of intermediate or high-risk myelofibrosis, a type of myeloproliferative disorder impacting the bone marrow, and polycythemia vera (PCV) if there is an inadequate response to or intolerance of hydroxyurea.
Considerable side effects have been associated with this therapy—see FDA label.
Led by Dr. Kirby, the investigational team will measure primary efficacy as the proportion of participants that achieve Hidradenitis Suppurative Clinical Response (HiSCR) at Week 16 with the topical treatment as compared to the beginning of the study. There must be at least a 50% reduction in the total abscess and inflammatory nodule count (AN count) for all study body sites with no increase in abscess count and no increase in draining fistula count relative to Baseline. This measurement of success will be used on all participants who complete the 16 weeks of treatment
Can a Diuretic drug called spironolactone be effective in treating HS in females?
The Medical University of South Carolina is planning a proof-of-concept study to determine if the Diuretic drug spironolactone (used to treat acne and male pattern hair growth in women) is effective in treating HS in females and which dose of the drug works best.
This study involves four clinic visits over a seven month period with the option to continue. The study starts on September 21, 2020, and will involve 60 HS patients. The study is led by Dirk Elston, MD, a well-known dermatology expert educated at Sidney Kimmel Medical College, Thomas Jefferson University.
Is Novartis’ Secukinumab, an interleukin-17 inhibitor superior to placebo for HS patients?
In a bid to compete against AbbVie’s Humira, Novartis sponsors the Phase 3 SUNRISE titled “Study of Efficacy and Safety of Two Secukinumab Dose Regimens in Subjects with Moderate to Severe Hidradenitis Suppurativa.” This multicenter, randomized, double-blind, placebo-controlled, parallel-group study includes two secukinumab dose regimens in a targeted 471 patients with moderate to severe HS. With the trade name Cosentyx, this is Novartis’ biggest-selling drug. Considerable warnings and cautions are associated with this powerful biologic, according to the FDA label. A human igG1k monoclonal antibody that binds to the protein interleukin-17a, the drug is currently marketed by Novartis for the treatment of psoriasis, ankylosing spondylitis, and psoriatic arthritis. The SUNRISE study started February 2019 with an estimated primary completion date of November 19, 2020, and a final completion date of September 23, 2021, according to a Novartis presentation.
Can a CD40 inhibitor and investigational anti-inflammatory product from Novartis effectively treat HS?
Based in Switzerland, Novartis targets two investigational drugs known as CFZ533 (iscalimab/a CD40 inhibitor) and LYS006 (anti-inflammatory) in a Phase 2 clinical trial targeting HS to assess preliminary efficacy and safety of the drugs in patients with moderate to severe HS and to further explore if the two investigational therapies possess an adequate clinical profile for further clinical development. With a goal of 90 participants in both Europe and the United States, the Phase 2 study commenced in February 2019 and is scheduled to be complete in May 2021.
Falling under Novartis’ “novel assets” category, Iscalimab, a CD40 inhibitor, has been identified as a target for Renal/Liver, Tx, Stevens-Johnson Syndrome (SjS) and HS. In a recent multicenter, randomized control trial (NCT02217410), with the primary endpoint of non-inferiority on the composite endpoint, the novel early-stage drug demonstrated non-inferiority on a composite clinical endpoint, improved renal function, reduced risk for new-onset diabetes and similar safety compared with tacrolimus. Readers should note that “non-inferiority” only means that the new therapy is not unacceptably less efficacious than an active control treatment already in use, making this approach at times questionable. An early-stage anti-inflammatory drug called LYS006 is under investigation by Novartis in the Immunology, Hepatology, and Dermatology therapeutic fields with an initial target of acne.
Can a topical antiseptic used for yeast infection improve HS conditions and hence the quality of life?
Wake Forest University launches a Phase 2 clinical trial this month to study the effect of a topical antiseptic used to treat many yeast infections called Gentian violet. Running through December 2020, the study team will enroll 16 participants with HS. Led by Rita Pichardo-Geisinger, MD, the investigatory team’s hypothesis is that gentian violet will help minimize skin trauma of active HS to promote improved wound healing and quality of life.
Can guselkumab help with moderate to severe HS?
Known as Tremfya and produced by Janssen (Johnson & Johnson), this monoclonal antibody and inhibitor of interleukin-23 is approved for the treatment of plaque psoriasis.
Back in September 2018, Janssen Research & Development LLC (Janssen) initiated a Phase 2 clinical trial investigating guselkumab in patients with moderate to severe HS. Called NOVA, the study targeted 184 adult patients with moderate to severe HS and will assess the efficacy, safety, and tolerability of the drug against a placebo. Still identified as “active” in Clinicaltrials.gov, the study record was just updated in May.
An estimated primary completion date of August 2020 rapidly approaches, so hopefully, some more information will be made available. The underlying intellectual property for this biological therapy is owned by a German company called Morphosys, which licensed its proprietary HuCAL antibody technology to Janssen in 2016.
Although the study results weren’t readily available according to academic authors from St. Vincent’s Trust and Belfast Health and Social Care Trust in a February article titled “Successful use of Guselkumab in the treatment of severe hidradenitis suppurativa,” the doctors reported a case of successful treatment of HS with this monoclonal antibody to the p19 subunit of IL-23. We should note that the drug has been identified as quite expensive, much like competitive biological therapies, such as Humira.
Can XBiotech’s (now Janssen) bermekimab successfully treat moderate to severe HS?
TrialSite News has not only reported on some positive news from this small Texas-based biotech, but also had an executive as a guest on the TrialSite News podcast series last year. Interestingly, shortly after the TrialSite News podcast, Janssen (a Johnson & Johnson company) announced its intention to acquire bermekimab from XBiotech. Shortly after that, Janssen finalized the deal for $750 million.
This study further evaluates the efficacy of bermekimab in treating moderate to severe hidradenitis suppurativa in adults. 1/3 of patients will receive weekly injections of bermekimab, 1/3 will receive alternating every other week injections of bermekimab or placebo, and 1/3 will receive weekly injections of placebo.
Targeting 120 participants with moderate to severe HS, the Phase 2, randomized, double-blind, placebo-controlled study of bermekimab commenced October 2019 and was planned to conclude in October 2020. It is possible that COVID-19 impacted the study timeline, like most studies. Well-known key opinion leader Alice Gottlieb, MD, with Icahn School of Medicine at Mount Sinai, serves as the study chair while the actual site is Tampa’s based ForCare Clinical Research.
Can a C5aR inhibitor help HS patients reduce symptoms?
A biotech company called ChemoCentryx is developing a lead candidate for their orphan and rare disease program called avacopan (CCX68). An orally-administered investigational product that inhibits the complement C5a receptor (C5aR) that the company hopes can be developed to help treat inflammatory and autoimmune diseases. This experimental drug blocks the activity of complement C5a, a component of the complement system, and the natural ligand for C5aR, reports the company.
The clinical trials started back in December 2018, and disclosures are supposed to end in December 2020. Notified as active and recruiting, it is possible that the study is behind its recruitment count—COVID-19 could certainly have an impact. The sponsor seeks in this randomized, double-blind, placebo-controlled, parallel-group Phase 2 study to test Avacopan in patients with mild to severe HS. With a 390 participant target, the industry sponsor discloses 95 clinical investigational sites across the United States. The study lead for the company is Peter Staehr, MD.
In a 2019 investor presentation, the company discloses its rationale for targeting HS; as that neutrophils has a suspected role in HS. Although host-defense defects in HS patients are suggested (not proven yet), hyperactive neutrophils have been proposed to be a factor in many chronic inflammatory diseases such as HS, where destruction of surrounding tissue occurs via the simultaneous release of reactive oxygen species and active proteases. The company’s economic indicator points to the fact that the only drug approved, Humira, still generates less than $1 billion—hence the opportunity.
Anticipating the interest in this study, in 2019, P&T Community reported that a milestone of interest for this study will be topline Phase 2 trial results for avacopan.
What is the safety and efficacy of using an approved Janus kinase (JAK) inhibitor discovered and developed by the NIH and Pfizer in HS patients?
Sponsored by the University of Colorado, Denver, and the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), this study investigates the use of an approved Pfizer drug called Tofacitinib (also sold as Xeljanz), used to treat rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, and ulcerative colitis. It should be that this drug represents considerable risk factors introduced recently—see below.
A February 2020 paper articulated that Tofacitinib showed benefit along with other therapies in recalcitrant HS patients. Considerable side effects can be reviewed at the FDA website. In 2019, the European Medicines Agency (EMA) reviewed tofacitinib and recommended that physicians, at least temporarily, not prescribe the 10 mg twice-daily dose to individuals at high risk for pulmonary embolism. U.S. regulatory warnings via FDA have focused on the risk of blood clots associated with this drug.
The FDA-approved drug is known to block IFN signaling in adults with Downs Syndrome as well as those with autoimmune, autoinflammatory skin disorders. The investigators will study the safety and efficacy of the treatment and include HS patients in this Phase 2 trial. Lead investigators include Joaquin Espinosa, PhD, with the Linda Crnic Institute, University of Colorado Anschutz Medical Campus and Cory Dunnick, MD, and David Norris, MD, both of the Department of Dermatology at the Anschutz Medical Campus. Their study started in 2020 and runs till 2024.
Can three (3) investigational kinase inhibitors help reduce symptoms of patients with moderate to severe HS?
Sponsored by Pfizer, one of the world’s largest pharmaceutical companies, the sponsor’s study seeks to identify the efficacy of three investigational kinase inhibitors—(PF 06650833), PF 06700841(Brepocitinib), and PF 06826647—in participants with moderate to severe HS. The study started back in December 2019 and runs till October 2021.
Does an interleukin-17 inhibitor called Siliq help patients with moderate HS?
In this study, a monoclonal antibody used to treat an inflammatory disease called brodalumb (trade name Siliq in the U.S. and Kyntheum in Europe) is tested to determine the efficacy in patients with moderate HS.
The drug was approved by the FDA to treat severe plaque psoriasis in people who hadn’t improved with other treatments, although there is an increased risk of suicide associated with the drug. Sponsored by Florida Academic Dermatology Centers with collaborator Ortho Dermatologics, the research investigators should be concluding the study, which involved a 24 week period including active therapy followed by a four-week observational visit. The total per patient study length was 28 weeks, and 20 patients were targeted by the protocol. The principal investigator for the study is Francisco A. Kerdel, MD. According to Clinicaltrials.gov, the trial is active and not yet recruiting, so TrialSite News will inquire into the status of this study.
Investigating the use of cannabis oil on HS patients in Israel—how about that?
As it turns out, some enterprising scientists have shown that cannabinoids reduce the follicular pilosebaceous activity most likely due to activating arachnoiditis, lipostat, anti-proliferative and anti-inflammatory agents and also reduce inflammation-inducing cytokines. Hence why To Pharmaceuticals, a privately-held cannabinoid-based pharmaceutical therapy company, launched a study last year. The company secured an exclusive license to utilize the pharmaceutical intellectual property developed by Tikun Olam Limited, a globally recognized pioneer of modern medical cannabis. The duration of this study has come and gone, and no results were disclosed. To Pharmaceutical’s CEO is Sid Taubenfeld. TrialSite News will reach out to the companies involved to learn if the study occurred. Led by principal investigator Dr. Michael Ziv, the study was planned to recruit participants at Haemek Hospital in Afula, Israel.
Call to Action: TrialSite News monitors these studies and can share updates as they are available. Sign up for the daily newsletter for ongoing updates.