New treatment enters phase 1 for wide range of inflammatory and autoimmune diseases.

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Inmagene Biopharmaceuticals announces that today the U.S. Food and Drug Administration (FDA) cleared its investigational new drug (IND) application for the drug candidate IMG-004, a non-covalent, reversible, third-generation Bruton Tyrosine Kinase (BTK) inhibitor, to proceed to the Phase I clinical trial. Inmagene is developing the drug candidate to potentially treat immunological diseases.

The planned Phase 1 study is a double-blind, randomized, placebo-controlled, single and multiple dose escalation study in healthy subjects. The study aims to explore IMG-004’s safety, tolerability, pharmacokinetics, and pharmacodynamics in healthy subjects.

“This is the third IND clearance Inmagene has obtained since the beginning of 2022,” said Dr. Jonathan Wang, Chairman and CEO of Inmagene. “These achievements have demonstrated Inmagene’s strong innovative capabilities and high efficiency.”

Dr. Jean-Louis Saillot, Inmagene’s Chief Development Officer, said, "BTK inhibition is an attractive target for a variety of inflammatory and autoimmune diseases, based on demonstrated activity or its current evaluation in clinical trials. IMG-004’s improved activity, selectivity, and pharmacokinetic profile in preclinical studies compared to those of other BTK inhibitors point toward a best-in-class potential. We look forward to the initiation of the IMG-004 clinical program with the hope of developing an innovative, safe and effective treatment option for patients with immunological diseases."

About IMG-004

IMG-004 is a non-covalent, reversible small molecule inhibitor targeting Bruton's tyrosine kinase (BTK). Designed specifically for inflammatory and autoimmune diseases that usually require long-term treatment, IMG-004 is potent, highly selective and brain permeable. It was originally discovered by HUTCHMED (China) Limited, with Inmagene assuming development responsibility at the candidate stage.

BTK is a non-receptor intracytoplasmic tyrosine kinase in the Tec family of protein tyrosine kinases. It is involved in innate and adaptive immune responses related to certain immune-mediated diseases.  Given the central role of BTK in immunity pathways, BTK inhibitors may offer a potential therapeutic approach for the treatment of a wide range of inflammatory and autoimmune diseases.

Not sure what this means exactly, I think it's just a formality but worth mentioning.

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UCB announced today that the U.S. Food and Drug Administration (FDA) has issued a Complete Response Letter (CRL) regarding the Biologics License Application (BLA) for bimekizumab for the treatment of adults with moderate to severe plaque psoriasis.

The letter indicates that the FDA cannot approve the application in its current form. The CRL states that certain pre-approval inspection observations must be resolved before approval of the application. We are cooperating with the FDA and are working to address these observations as expeditiously as possible.

UCB is committed to bringing bimekizumab to patients worldwide. In August 2021, bimekizumab received marketing authorization in countries of the European Union (EU)/European Economic Area (EEA) and Great Britain, for the treatment of moderate to severe plaque psoriasis in adults who are candidates for systemic therapy. In January 2022, bimekizumab received marketing authorization in Japan for the treatment of plaque psoriasis, generalized pustular psoriasis and psoriatic erythroderma in patients who are not sufficiently responding to existing treatments. In February and March 2022, bimekizumab received marketing authorization in Canada and Australia, respectively, for the treatment of moderate to severe plaque psoriasis in adults who are candidates for systemic therapy or phototherapy.

In context of the CRL, UCB is reviewing its financial guidance for 2022.

Haven’t posted for a looooooooong time!!

I’ve been successfully using adalimumab (humira first then a different brand for the last couple of years) for about 5 years and been pretty much completely clear, however the last couple of months I have started to show a rash all over my chest/shoulders/back.

It’s not the same as the P I had before Humira, it is flat, not itching, no dryness just smooth red blotches of skin. Could this be a different form of P?? Could it be that it’s time to change my treatment??

Feeling a bit apprehensive!!

This study looked at the prevalence and characterization of treatment-refractory psoriasis and super-responders to biologic treatment.

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Introduction
Treatment with biologics often leads to clearance of psoriasis. However, some patients do repeatedly fail to respond and/or lose an achieved response (treatment refractory) to the biologic, whereas other patients achieve excellent response to one biologic and remain clear of psoriasis for several years (super-responders).

Objective
To identify and characterize patients with treatment refractory psoriasis and patients who are super-responders to biologic treatment.

Material and methods
Patients registered in DERMBIO between January 2007 and November 2019 were included. Patients were categorized as being treatment refractory if they had had treatment failure to ≥3 biologics targeting ≥2 different pathways. Super-responders were patients treated with their first biologic for minimum 5 years without an absolute psoriasis area and severity index (PASI) > 3 between 6 months and 5 years of treatment. All remaining patients from DERMBIO served as comparators.

Results
In total, 3280 patients were included with a mean age of 45.0 years. 1221 (37%) of the patients were females. Of the included patients, 214 (6.5%) were categorized as treatment refractory and 207 (6.3%) were categorized as super-responders. Treatment refractory patients had higher mean body weight (100.6 kg vs. 90.6 kg, P < 0.0001) and higher mean BMI (32.2 vs. 29.4, P < 0.0001) compared with the rest of patients in DERMBIO. Super-responders had higher socioeconomic status and fewer comorbidities compared with the comparator group (P < 0.0001).

Conclusion
A small proportion of patients with psoriasis treated with biologics are either super-responders or treatment refractory. Treatment refractory patients have higher body weight, whereas super-responders have fewer comorbidities and higher socioeconomic status.

This study tried to understand secretory leukocyte protease inhibitor (SLPI) and psoriasis.

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Background
Secretory leukocyte protease inhibitor (SLPI), a ~12 kDa protein is an important regulator of innate and adaptive immunity and a component of tissue regenerative programs. SLPI expression is markedly elevated in chronically inflamed skin, including that of individuals suffering from psoriasis. However, the role of SLPI in these diseases remains elusive.

Objectives
The poor understanding of the early stages of the development of psoriasis is a major obstacle to successful intervention in the skin pathology. We hypothesized that SLPI and peripheral nerves that might be activated early in the progression of the disease likely form a functional relationship to maintain skin barrier homeostasis and respond to a variety of threats.

Methods
We used skin biopsies of healthy donors and individuals with psoriasis to show expression pattern of SLPI. A role of SLPI in psoriasis was mechanistically assessed using SLPI deficient mice and an imiquimod-induced experimental model of psoriasis.

Results
We show that mice lacking SLPI had exaggerated skin alterations that extended beyond the treatment site in an imiquimod-induced psoriasis. The spatiotemporally distinct skin responses in SLPI deficient mice, compared to their wild-type littermates, resulted from a compromised skin barrier function that manifested itself in heightened transepidermal water loss through the larger skin area surrounding the imiquimod challenged skin. The increased pathogenic skin changes in the absence of SLPI were reversible through pharmacological treatment that blocks a nerve-reflex arc.

Conclusions
Together these data indicate that SLPI plays a protective role in psoriasis through preventing skin dryness, inherent in the pathogenesis of psoriasis, and that this SLPI action depends on neuronal input operating in a reflex manner. These findings reveal a previously unrecognized mechanism that maintains cutaneous homeostasis which involves a crosstalk between the nervous system and a protein anatomically poised to fortify the epidermal permeability barrier.

Just wondering.  This is my hand.  And my fingernail with a little pitting.  

This study looked at the efficacy response rates and safety outcomes through 120 weeks for patients with moderate to severe psoriasis who are treated with Siliq / Kyntheum (brodalumab)

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Background
Brodalumab is a monoclonal antibody that blocks multiple interleukin-17 family cytokines by binding to the shared A subunit of the interleukin-17 receptor. In Phase 3 trials, brodalumab provided high levels of skin clearance through 52 weeks in patients with moderate-to-severe psoriasis and was generally well tolerated.

Objectives
To assess efficacy response rates and safety outcomes through 120 weeks for patients with moderate-to-severe psoriasis who received brodalumab.

Methods
Safety and efficacy data were pooled for patients from AMAGINE-2 and -3 who received continuous brodalumab 210 mg every 2 weeks, or brodalumab 210 mg every 2 weeks after receiving either brodalumab 140 mg or placebo through Week 12. Efficacy data are presented using observed data, non-responder imputation (NRI), and a combination of NRI and missing at random assumption to account for missing data. Absolute PASI scores are presented using mixed-effect model repeated measure modelling and multiple imputation.

Results
Based on observed data at Week 120, 86% of the continuous brodalumab 210 mg group achieved PASI 90 and 74% achieved PASI 100. At Week 12, 58% of this group achieved absolute PASI ≤1; this proportion increased to approximately 80% at Week 52 and persisted through Week 120.
Among patients receiving continuous brodalumab 210 mg, median duration of brodalumab exposure was 747 days, and the overall exposure-adjusted event rate of treatment emergent adverse events per 100 patient-years was 329. Safety through 120 weeks was comparable to the results of the primary AMAGINE-2 and -3 studies. Patients who switched to brodalumab 210 mg after receiving either brodalumab 140 mg or placebo through Week 12 showed similar skin clearance and safety profiles.

Conclusions
Brodalumab treatment was well tolerated and resulted in high levels of skin clearance that were rapidly achieved and maintained through Week 120, supporting its long-term efficacy and safety profile.

I was diagnosed with Ps 2 years ago but I've had PsA for a decade. I have had sporadic issues with depression long before I had this disease so I can't blame everything on Ps! I know what standard depression feels like and this feels different. It hits me like a ton of bricks then it goes away after 10 days or 2 weeks. That isn't, in my experience, how depression works. If I get on antidepressants, by the time they kick in, I feel better. I don't think I have what most shrinks wound consider your run off the mill depression. Has anyone experienced anything like this or is it unique to me? I started a journal to try and pinpoint how and why, but it will likely take a while for me to see a pattern.

I just want some advice from someone who knows what I'm going through. I don't want to divulge much more info on here than I already have so a pm would be better.

Hi - 


Newbie here, hello everyone.



After suffering from psoriasis for >30 years I have yet another consultant appointment this week. I have been using Enstilar effectively over the last year or so which does help but I have so many patches its becoming unmanageable (plus it makes me feel like I could swim the channel I'm so greasy).



I've had light treatment several times which has been effective but the psoriasis returns quite quickly afterwards.



My guess is that I will get offered Methotrexate from the consultant but I really want to avoid having to take it, with all the known side effects and lifestyle modifications. There are some much newer, more effective treatments that I would like to try. I wondered if anyone else has had a similar situation or suggestions on how to drive the discussions. 


Thanks for reading.

I'm new to forum so first of all, hello all! 

I was on Otezla for 2 years and then got on Tremfya 3 months ago. Tremfya was basically as effective as an injection of saline so I'm back on Otezla which does a decent job but not fantastic. Any advice or recommendations?

This months poll above asks: What effect has Exercise had on your psoriasis and/or psoriatic arthritis ?

Voting is open to members and guests and our members can also leave a comment if they wish.

I learned the hard way this week.  No matter that I keep the shower stall clean, using a squeegee on the walls and floors, drying with a cloth after showering.  Each time I shower, the moisturizer creams or the coconut oil makes the shower stall floor slick.

I'd forgotten my razor on the bathroom counter and turned off the shower's flow, quickly stepped out of shower to fetch the razor, quickly hopped back into the shower stall to shave my legs.  A sudden loss of balance and nothing to be done for it.

I fell against the stall's built-in bench, striking my side between my ribs and hip on Tuesday.  I was temporarily immobilized by pain and could only call out in agony.  My partner rushed in, assessed the crisis, covered me with a towel, and sat on the floor nearby until I could move.  

The rest of Tuesday was pained with little mobility.  I slept sitting up.  On Wednesday, a trip to "same day" care for doctor and x-rays took three hours.  But nothing was broken. Kidney is okay.  Heart is okay.  I got prescriptions for Tramadol and Lidocaine Patches.  

I'm resting and hoping to be able to work on Saturday.  

So this is my warning to not try gymnastics in the shower or bath if you are also using moisturizers and/or coconut oil.  (And it's my appeal for sympathy since it still hurts, even though it's 70% better than Tuesday.)

I have to say it’s the best one I’ve seen or been in, it’s easy to navigate and welcoming.
I like the non psoriasis boards a lot too, because although at times psoriasis can be a bit all consuming when you are itchy, sore or whatever, there’s much more to life and it really gives shape to those who take part. If it were just about the P I would probably only pop in occasionally.
I wouldn’t feel comfortable giving the information I give here on other forums but I am very happy with Fred’s approach and I know he and others are keeping watch on it all.

In fact the question is: “Why has Psoriasisclub the nature that we see?”

I think there are a lot of factors that play a role in the nature of Psoriasisclub.
I visit other forums some times, of many kinds and types, e.g. photography, motorcycles, sometimes a technical forum though they are hard to understand, etcetera.
They are mostly helpful also, but have a different atmosphere.

Sometimes I visit facebook psoriasis sites, facebook is kind of a fehtherlight streaming forum with a very low span of attention. And over there I read a lot of nonsense and weird idea on psoriasis. There is a forum of the dutch association, where I sometimes post. They are reasonably good, but there is not so much activity.

So that winds back to partly what Forest said about psoriasisclub concerning adverts and integrity. But there is more to psoriasisclub.
There is knowledge and experience over here. The members together have gathered immense experience, without forcing that experience to others. They tell other members with questions about their personal experiences with medication or show the way to members that do have experience.
It is a factor that is greatly missed by industry.  Yes there is scientific research and statistical proof, but to gain real insight you must dive in to personal experiences.

The strong point is that psoriasisclub has grown into a group of knowledged and friendly friends, spread out over the world, who have never met each other, mostly have never seen each other, but still are friends.

The club has, thanks to Fred, a number of simple rules where above all the rule is to respect each other, and for some reason that really works very well with psoriasisclub.

The club also thanks to Fred, has always the newest news facts about psoriasis and Psoriatic Arthritis. I have never seen that anywhere else. I even know that e.g. in the Netherlands the medical inspections (IGJ) has the weird philosophy that this kind of news should not given to patient as not to give them too much hope. Now that is a weird philosophy. 

The club also has a lot of humour and interesse in each other’s life outside the psoriasis life. Half of what is posted is not about psoriasis but about a lot of other things in life, where we all have our opinions about, sometimes very different and the way that we discuss that has already learnt me lot of things and sometimes changed my view to things that I was sure of.

And last but not least the club has a great Staff…    Kind of weird combination… a cow girl from the States, a fossil seeking gentleman from England, an English speaking hermit living unfindable in the country of France and a Dutch motorcycle girl dancing through life.

But…. It all works.    and I bet this is not all that can be said about psoriasisclub.

I'm just going to whine.  The nausea and headaches with oral MTX are bugging me.  I'm seeing my dermatologist on Tuesday and will ask about switching to the injectable, as Dave recommended.  But I also miss sharing a glass of wine with my partner.  And I would like to enjoy a bourbon, now and then.  

The MTX has been working, though.  But the nausea and headaches are not so fun.  Possibly, the headaches would persist with the injectable form, even if the nausea abates.  

I'm going to read up on Interleukins and try to understand them.  My gastroenterologist said that Stelara works for both Crohn's and Psoriasis.  Humira targets TNF-alpha, not the interleukins.  

I'm grateful for the information on these various medications in Psoriasis Club.

Some of us have had psoriasis since childhood, some got it/ realised they had it later on in life.

But can you remember if you knew what it was and were more than vaguely aware of psoriasis before you had it?

This months poll above asks: What effect has Food had on your psoriasis and/or psoriatic arthritis ?

Voting is open to members and guests, you can choose more than one option and our members can also leave a comment if they wish.

Following on from this thread Bimzelx for psoriasis two year data UCB have released phase 3 results ofr treating psoriatic arthritis.

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UCB today announced positive top-line results from the Phase 3 BE COMPLETE study, which evaluated the efficacy and safety of BIMZELX® (bimekizumab) in the treatment of adults with active psoriatic arthritis, who were inadequate responders or intolerant to anti-tumor necrosis  factor-alpha (anti-TNF-α) therapy.

BE COMPLETE met its primary endpoint, demonstrating that significantly more patients treated with bimekizumab achieved 50 percent or greater improvement in signs and symptoms of disease from baseline, compared with placebo, as measured by the American College of Rheumatology (ACR) 50 response at week 16.

The study also met all ranked secondary endpoints. Bimekizumab showed significant improvements over placebo at week 16 in physical function, as measured by Health Assessment Questionnaire-Disability Index (HAQ-DI); skin clearance, as measured by at least a 90 percent improvement in the Psoriasis Area and Severity Index (PASI90); physical health status, as measured by the Short Form 36-item Health Survey (SF-36) Physical Component Summary (PCS) score; and low disease activity, as measured by the Minimal Disease Activity (MDA) index.

“The BE COMPLETE results mark the latest positive data in a series of four Phase 3 readouts for bimekizumab in the treatment of psoriatic arthritis and axial spondyloarthritis. We believe that these consistent and robust results have the potential to elevate the standard of care for patients, “Both psoriatic arthritis studies in the program used ACR50 as the primary outcome measure. The positive findings in both studies highlight the clinical potential of bimekizumab in psoriatic arthritis for both biologic naïve and anti-TNF therapy experienced patients.”

In BE COMPLETE, the safety profile of bimekizumab was consistent with safety data seen in previous studies with no new observed safety signals. The safety and efficacy of bimekizumab in psoriatic arthritis have not been established, and it is not approved for use in psoriatic arthritis by any regulatory authority worldwide.

The top-line results from the BE COMPLETE study build on the positive top-line interim analysis results from the Phase 3 BE OPTIMAL study in adults with active psoriatic arthritis, who were biologic disease-modifying anti-rheumatic drug (bDMARD) naïve, reported in November 2021. Based on these results, UCB plans to submit regulatory applications for bimekizumab in psoriatic arthritis in the United States and the European Union in Q3 2022.

I have a bad flare up after stopping Simponi (too much skin cancer to manage). I am sooooooo fatigued and wonder if that is caused by the flare up or the general state of the world. 

Do others experience exhaustion with a flare up? 

J

Glad to find this forum. I recently moved to Oregon and the care protocol is very different than where I lived in California. Here I am seen by a physician’s assistant only. Besides seeing patients for diseases of the skin, the office sees a lot of clients for Botox, cellulite treatment and who knows what else (I delete the ads they send me.)

After being on Simponi for probably 8 years, I started getting a lot of skin cancer ( new ones popping up weekly) and had to have surgery on spots on my legs 4 times in 3 months. My new rheumatologist said that increased skin cancer was a side effect of Simponi. I stopped the Simponi in December and have fewer incidence of skin cancer already (only planning two surgeries next month!)

However, my psoriasis has flared with a vengeance. I have it all over, including places that I haven’t ever had it (in 45 years with PA). Interestingly my psoriatic arthritis hasn’t flares without Simponi.

My dermatologist Physician’s assistant suggested Skyrizi and asked me to consult with my rheumatologist. (In California, the doctors would have talked directly to come up with a plan…)

My rheumatologist said that Skyrizi wasn’t authorized for PA and suggested Otezla, telling me to discuss with my dermatologist. I decided to try Skyrizi but the dermatologist says now it wouldn’t be appropriate since I have PA. (Huh? I wouldn’t have known of the drug if he hadn’t mentioned it). He said we will talk in a month. 

I am frustrated, itching and moisturizing constantly. Daily new spots appear. 

I’d like to see a doctor who specializes in psoriasis and skin cancers. Does anyone know of a dermatologist near Ashland or Medford Oregon? I looked at the USA psoriasis site and one doctor is listed. Haven’t heard of her or her practice group, but I’ll call tomorrow to see what her focus is.

Sorry for the long —and whiny— intro. But, I know you guys get it. Thanks.