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KSL Beutner Laminin Blood Test

Highly accurate IIF serological assay for Laminin 332 Mucous Membrane Pemphigoid reduces the wait for confirmed diagnosis from months or years to 72 hours or less

On July 27, 2022 KSL Beutner Laboratories (Beutner), a global leader in immunologic testing for the diagnosis of bullous, vascular, connective tissue and inherited skin diseases, announced the launch of a first-to-market indirect immunofluorescence (IIF) serum blood test in the U.S. that positively identifies laminin 332, an antigen associated with the chronic, debilitating autoimmune disease mucous membrane pemphigoid (MMP).

Without a definitive interpretation, patients experience considerable pain and suffering due to misdiagnosis and treatment delays. Long sought after by oral pathologists, oral surgeons, periodontists and dentists, in addition to dermatologists, Beutner’s laminin 332-specific serological assay reduces the time to confirmed diagnosis from as much as two years to 72 hours or less. 

“The development and launch of Beutner’s much-anticipated serological assay for laminin 332 MMP builds on the pioneering work of Dr. Ernst Beutner, the father of immunodermatology,” said Dr. Lakshmanan Suresh, Technical Director at Beutner and Chief Medical Officer of KSL Diagnostics, Inc. (www.ksldx.com), which counts Beutner among its clinical laboratories. “The innovative methods he established for diagnosing autoimmune blistering diseases are used worldwide, and we are proud to continue his legacy.”

MMP is an autoimmune blistering disease characterized by multisite lesions on mucous membranes. Anti-laminin 332 MMP lesions often scar and can lead to serious complications depending on the mucosal surfaces affected. Oral mucosa — gums, inner lining of the cheeks and lips, palate and tongue — are involved in 80-90% of cases. Scarring of ocular mucosa, present in half of patients, may lead to blindness. The disease can also impact mucous membranes in the nose, throat, genitals and anus, causing severe, irreversible damage. Another complication in 25-30% of patients is increased risk of cancer malignancies, primarily adenocarcinoma in the gastrointestinal and genital mucosa and lungs. The condition can be fatal if left untreated. Considered a rare disease of unknown cause, MMP occurs mainly in people between ages 60 and 80 and, infrequently, in children. Women are affected twice as often as men.

“The first assay of its kind available in the U.S., Beutner’s IIF serum blood test verifying the presence of specific autoantibodies for laminin 332 MMP now enables clinicians to accurately identify this hard-to-diagnose disease much faster,” said Dr. Raminder Grover, Laboratory Director at Beutner. “This in turn allows for available therapies to be started much earlier to alleviate patients’ significant ongoing discomfort and spare them the long-term medical complications of this devastating disease.”

The most common autoantigens associated with MMP are BP180 and laminin 332. About one-third of patients are afflicted with the laminin 332 variant. Since 2002, blood tests to detect BP180 have been widely available, but a laminin 332 serum test has not been approved in the U.S. until now. Anti-laminin 332 MMP cannot be differentiated from other forms of the disease based on clinical examination. It can only be distinguished by a serological test for IgG antibodies of the variant. Because it mimics other diseases in the mouth, patients may suffer increasing pain and decreased quality of life for six months to two years before obtaining conclusive test results. Reaching a positive diagnosis as soon as possible is critical so that physicians can begin treatment.

Confirming laminin 332 MMP relies on several laboratory tests offered by Beutner: first, a direct immunofluorescence (DIF) microscopy of a skin biopsy to detect tissue-bound immunoreactants. Although DIF is the gold standard for investigating all forms of MMP, it does not always differentiate between variants. Next, indirect immunofluorescence is applied to identify circulating antibodies targeting the autoantigens in the basement membrane zone (BMZ) of the skin. This type of analysis is done in two parts – an IIF test on salt-split skin and an IIF serum test on transfected cells for laminin 332 IgG/IgG4 antibodies using a EUROIMMUN assay. Beutner’s IIF serological assay has a sensitivity of 84% and a specificity of 99%.

Beutner recently received approval from the New York State Department of Health to perform the laminin 332 IIF blood test for U.S. customers at its Buffalo, NY lab.

Dr. Ernst H. Beutner, a co-founder of Beutner Laboratories, pioneered the DIF test 40 years ago after he and his associates at the University at Buffalo (UB) discovered the role of autoimmunity in pemphigus and pemphigoid. Development of defined, quantified immunofluorescent methods now used worldwide for the investigation of autoimmune skin diseases began with studies at UB led by senior researchers from Beutner, UB and Harvard University.

KSL Beutner Laboratories provides anti-laminin 332 IIF serological testing as a service, as well as several other assays for laminin 332 MMP and for the BP180 variant of MMP. Tests can be ordered at https://www.beutnerlabs.com/.

Beutner Laboratories

Akari Therapeutics recently announced that positive results from the Phase II study of investigational nomacopan in bullous pemphigoid (BP) were published online in the Journal of the American Medical Association (JAMA). 

“These positive Phase II data advanced our understanding of the nomacopan safety profile and informed duration of treatment in the ARREST-BP Phase III clinical trial, which is open for enrollment now,” said Rachelle Jacques, President and CEO of Akari Therapeutics.

BP is the most common autoimmune blistering skin disease. It typically affects people over the age of 65. There are no approved therapies but superpotent topical steroids and high dose oral corticosteroids (OCS) are the current standard of care. The mortality rate in BP is ~three-fold higher than the general population due to the disease itself, and infections and cardiovascular conditions that are more common in older patients and are exacerbated by treatment with high dose OCS. There is significant unmet need for an effective steroid-sparing therapy.

Read the full press release here. 

April 28, 2021 (GLOBE NEWSWIRE) — Akari Therapeutics, Plc, a biopharmaceutical company focused on innovative therapeutics to treat orphan autoimmune and inflammatory diseases where the complement and leukotriene systems are implicated, today announced that the FDA has granted Fast Track designation to nomacopan for the treatment of patients with moderate and severe bullous pemphigoid (BP). Nomacopan has also been granted orphan drug designation for nomacopan for the treatment of BP by the FDA and the European Medicines Agency (EMA).

Fast track is a process designed to facilitate the development and expedite the review of drugs to treat serious conditions and fill an unmet medical need. The purpose is to get important new drugs to the patient earlier. A drug that receives Fast Track designation benefits from more frequent communications and meetings with the FDA to review the drug’s development plan including the design of the proposed clinical trials, use of biomarkers and the extent of data needed for approval.

Success in BP could potentially open up a range of other severe dermatological conditions for treatment with nomacopan where C5 and LTB4 are implicated, including hidradenitis suppurativa, epidermolysis bullosa acquisita and mucous membrane pemphigoid.

Read the full press release here. 

Cabaletta Bio, Inc., a clinical-stage biotechnology company focused on the discovery and development of engineered T cell therapies for patients with B cell-mediated autoimmune diseases, announced on May 6, 2020 that the U.S. Food and Drug Administration (FDA) has granted Fast Track Designation for DSG3-CAART (Desmoglein 3 Chimeric AutoAntibody Receptor T cells), the Company’s lead product candidate for treatment of mucosal pemphigus vulgaris (mPV), for improving healing of mucosal blisters in patients with mPV.

“We believe that this Fast Track Designation, coming shortly after the Orphan Drug Designation for DSG3-CAART, further demonstrates that mPV is a devastating, rare disease for which patients have limited treatment options resulting in a large unmet need. The Fast Track Designation represents an important next step in our clinical development plans,” said David J. Chang, M.D., Chief Medical Officer of Cabaletta. “We appreciate the benefits provided by this designation, including the opportunity for increased access to the FDA and potential acceleration of our clinical development path and regulatory review process.”

The FDA grants Fast Track Designation to drugs or biologics to facilitate the expedited development and review for therapeutics intended to treat serious or life-threatening conditions and to address unmet medical needs. Companies that receive Fast Track Designation are eligible for several potential benefits including the opportunity for more frequent meetings and interactions with the FDA during clinical development as well as eligibility for accelerated approval and/or priority review, if relevant criteria are met. Companies may also be allowed to submit sections of their Biologics License Application (BLA) on a rolling basis.

Read the full press release. 

Cabaletta Bio, Inc., a clinical-stage biotechnology company focused on the discovery and development of engineered T cell therapies for patients with B cell-mediated autoimmune diseases, announced on January 29, 2020 that the U.S. Food and Drug Administration (FDA) has granted Orphan Drug Designation for the Company’s lead product candidate, DSG3-CAART, for the treatment of pemphigus vulgaris (PV). DSG3-CAART is designed to target the cause of mucosal PV (mPV), B cells that express pathogenic autoantibodies directed against the DSG3 protein, while preserving normal B cell immune function.

“Mucosal pemphigus vulgaris is a rare and potentially fatal, chronic autoimmune disease characterized by the loss of adhesion between cells of mucous membranes, resulting in widespread damage, painful blisters of the mucosal membranes, and increased susceptibility to life-threatening systemic infections,” said David Chang, M.D., Chief Medical Officer of Cabaletta. “For affected patients, despite current treatment options, there is an urgent unmet need for more effective and durable therapies that can provide reliable, complete, and persistent remission from the disease beyond general immune suppression and B cell depletion provided by current treatment options. Orphan Drug Designation is an important recognition for investigational therapies for rare diseases and provides us with potentially valuable benefits as we prepare to initiate the DesCAARTes trial to generate and then report acute safety data from the first cohort of patients by the end of 2020.”

The FDA grants Orphan Drug Designation to drugs or biologics intended to treat or prevent rare diseases or conditions that affect fewer than 200,000 individuals in the United States. This designation qualifies Cabaletta for certain incentives, which may include partial tax credit for clinical trial expenditures, waived user fees and potential eligibility for seven years of marketing exclusivity.

Read the full press release.

23 patients were evaluated for efficacy in an adaptive Phase 2 trial aiming to establish optimal treatment regimen

argenx, a clinical-stage biotechnology company developing a deep pipeline of differentiated antibody-based therapies for the treatment of severe autoimmune diseases and cancer, released a strategic outlook for 2020 outlining key priorities for its broad pipeline and path towards achieving its ‘argenx 2021’ integrated commercial vision.

“We begin 2020 in an exciting position, having met all our objectives for our clinical programs. This includes the completion of enrollment of our Phase 3 ADAPT trial of efgartigimod in gMG, the launch of key efgartigimod clinical trials in ITP and CIDP, and the initiation of cusatuzumab clinical trials in two AML settings with Janssen. In addition, we’re announcing today positive proof-of-concept data for efgartigimod in PV, our third ‘beachhead’ indication, further demonstrating our initial development strategy of targeting pathogenic autoantibodies and creating commercial opportunities in several therapeutic areas. Looking forward to the remainder of 2020, we plan up to five registrational efgartigimod trials and further expansion of the cusatuzumab global development plan with Janssen,” said Tim Van Hauwermeiren, Chief Executive Officer of argenx.

“Most importantly, we are continuing to execute on the ‘argenx 2021’ vision to become a global, integrated immunology company with our first launch of efgartigimod in gMG expected in 2021. At the core of this growth strategy is a commitment to expanding our early-stage pipeline with immunology breakthroughs and advancing our late-stage candidates while extending our reach to bring first-in-class medicines to patients,” continued Mr. Van Hauwermeiren.

argenx 2021 Vision

argenx continues to execute on its plan to become a fully integrated immunology company through its “argenx 2021” vision, including building two initial commercial franchises in neuromuscular indications and hematology/oncology and expanding its global presence encompassing Boston, Ghent and Tokyo. As part of this vision, argenx highlights:

Leadership in FcRn and its therapeutic immunology potential:

  • On track to launch first FcRn antagonist with efgartigimod in generalized myasthenia gravis (gMG) in 2021
  • Up to five registrational trials expected to be ongoing in 2020 across four targeted indications (gMG, immune thrombocytopenia (ITP), chronic inflammatory demyelinating polyneuropathy (CIDP) and pemphigus vulgaris (PV))
  • Fifth efgartigimod indication expected to be announced in 2020
  • Further research underway exploring therapeutic potential of FcRn modulation

Read the full press release.

Genentech, a member of the Roche Group, announced data this week from the Phase III PEMPHIX study evaluating the efficacy and safety of Rituxan® (rituximab) compared to mycophenolate mofetil (MMF) in adults with moderate to severe pemphigus vulgaris (PV). The study met the primary endpoint at week 52 and demonstrated that Rituxan is superior to MMF, with 40.3% of patients treated with Rituxan achieving sustained complete remission (CR) without the use of steroids for 16 consecutive weeks or more, compared to 9.5% in the MMF arm (p<0.0001). All secondary endpoints were statistically significant in favor of Rituxan: lower cumulative oral corticosteroid dose (mean difference: 1595 mg; p=0.0005), fewer flares (6 vs. 44, p<0.0001), a greater likelihood of sustained CR (hazard ratio [HR]=4.83; p=0.0003), a lesser likelihood of flare (HR=0.15; p<0.0001) and a greater improvement in the Dermatology Life Quality Index (DLQI) at week 52 (estimated mean change from baseline -8.87 vs. -6.00, p=0.0012) compared to the MMF arm. Adverse events were generally consistent with those seen in previous Rituxan clinical studies in PV and other approved autoimmune indications.

“The approval of Rituxan for the treatment of pemphigus vulgaris was the first major advancement in the treatment of this rare, serious disease in more than 60 years,” said Levi Garraway, M.D., Ph.D., chief medical officer and head of Global Product Development. “The PEMPHIX study showed that 40% of people in the study could achieve complete remission from painful blistering without the need for corticosteroids for 16 weeks or more and that Rituxan may be a superior treatment option to mycophenolate mofetil.”

The study is ongoing, with patients participating in a 48-week safety follow-up period after treatment completion or discontinuation.

Read the full press release.

Cabaletta Bio, Inc., a clinical-stage biotechnology company focused on the discovery and development of engineered T cell therapies for the treatment of patients with B cell-mediated autoimmune diseases, announced this week that it has received clearance of its Investigational New Drug (IND) application from the U.S. Food and Drug Administration (FDA) to initiate a first-in-human clinical trial of desmoglein 3 chimeric autoantibody receptor T cells (DSG3-CAART) in patients with mucosal pemphigus vulgaris (mPV) to assess the safety and tolerability of DSG3-CAART in these patients. The Company anticipates enrolling the first patient in 2020.

“The FDA’s clearance of our IND for DSG3-CAART is an important milestone for patients with mPV and the first IND clearance for a product candidate from our Cabaletta Approach to selective B cell Ablation (CABA™) platform,” said Steven Nichtberger, M.D., Chief Executive Officer and Co-Founder of Cabaletta Bio. “DSG3-CAART is the first of several CAAR T cell product candidates in our announced pipeline, which includes product candidates targeting patients with MuSK myasthenia gravis, the mucocutaneous form of pemphigus vulgaris (PV), and hemophilia A patients with inhibitors to factor VIII therapy.”

mPV is a potentially fatal, B cell-mediated chronic, rare autoimmune disease that causes painful blisters and sores on mucous membranes of affected patients, leading to severe and sometimes debilitating and life-altering effects. DSG3-CAART is designed to selectively target and eliminate B cells expressing autoantibodies specific for DSG3 that are the cause of mPV while preserving healthy B cell immune function. DSG3-CAART has the potential to generate persistent complete remission off therapy while avoiding the adverse effects of chronic and generalized immunosuppression. Currently available treatment options induce broad immunosuppression, which put the patient at risk of infection and often provide only transient complete remission with subsequent relapses for patients with moderate to severe mPV. Approximately 4,250 patients suffer from mPV in the United States and 6,250 patients in Europe, which accounts for approximately 25% of all PV cases.

Read the full press release.

On April 23, 2019, Akari Therapeutics, Plc (Nasdaq: AKTX), a biopharmaceutical company focused on innovative therapeutics to treat orphan autoimmune and inflammatory diseases where the complement and/or leukotriene systems are implicated, announced positive initial Phase II clinical data from the first three of bullous pemphigoid (BP) patients in an ongoing clinical trial.

Bullous pemphigoid is a severe orphan inflammatory skin disease currently treated primarily with steroids and immunosuppressants which bring with them well known side effects. Treatment response and steroid potency varies significantly based on the severity of the disease, although flares and relapses frequently occur.

In patients with bullous pemphigoid there is evidence that both terminal complement activation (C5) and the lipid mediator leukotriene B4 (LTB4) have a central role in driving the disease. Ex vivo data, from a recent study at Lubeck University, in BP patients showed a pronounced accumulation of LTB4 and C5 and its activation products in the inflamed skin of bullous pemphigoid disease patients.

The Phase II trial for up to nine mild-to-moderate bullous pemphigoid patients is a six-week open-label single-arm study evaluating safety and with the main efficacy measure the Bullous Pemphigoid Disease Area Index (BPDAI) a frequently used evaluation of the extent and severity of the disease.

Initial results from the first three patients showed that Nomacopan (Coversin), dosed daily subcutaneously, was well tolerated in three elderly patients (>65 years), and that there were no drug-related adverse events.

Read the full press release here. 

My name is Marlis Lippow, and I reside in Northern California. I participated in a randomized, double-blind, double dummy study evaluating rituximab infusions vs. 2,000 mg of mycophenolate mofetil (Cellcept®).  I had previously received rituximab infusions so I had a pretty good idea of what to expect if I was to again receive it. I had three previous rounds and my doctor said the effects should last about six months, after which I would probably need another round. I was lesion-free for about seven months before the lesions started to return. I also was on CellCept and prednisone, so I know how those affect me.

Learning About the Trial

My doctor mentioned a clinical trial, answered my many questions, and asked me to think about it.  I returned a month later for a followup appointment and there was another doctor present. She was talking about the trial and it seemed she expected me to be a part of it. I was still unsure and had more questions. She did explain that before I could be accepted, I’d undergo a screening (ECG, chest x-ray, and blood work). That was great, I would find out how I am doing. If I passed the tests, I could decide if I wanted to participate. The trial included a stipend, $50 for each session for gas and parking. That sounded good since I live about 45 miles away.

Making the Decision

My doctor and I discussed the pros and cons of the assorted medications and what I’d need to take if I did not participate in the trial but still needed rituximab. Either way, the side effects are not pleasant.  Basically, we talked about the lesser of the two evils.

I learned my doctor is referred to as the Principal Investigator (PI) and the other doctor is the Sub-Investigator (SI). The SI would be seeing me every month. Since the SI is not my primary doctor, it is very important she have a complete grasp of my medical history. During my visits I would have blood work and urinalysis done. The PI would get the test results and be aware of my progress and any possible problems. If he felt there was a concern, he would end my participation in the study.

I also learned I could opt out of the study at any time if I became uncomfortable.

In the end, I chose to be in the trial.

My Trial Experience

Throughout the study, I felt my doctor was most concerned about my well-being, as he should be. He even called me in between visits and that gave me a good, positive feeling.

I received two initial infusions two weeks apart. After about five months, I received two more, also two weeks apart. By the third round I no longer had any sores.  I was told that I was “controlled” and after the last infusion, I’d be in remission! My doctor told me this remission should last anywhere from six months to three years. I am hoping it will be longer!

Don’t be worried about the infusions.  The infusion nurses are angels and take wonderful care of you! They are kind, let you know what to expect, and give you an idea of how you will feel.  If you have any questions, you will have the phone numbers for the PI and SI and are encouraged to use them.

Clinical trials are not for everyone. In fact, there are many qualifying and disqualifying criteria set by the drug manufacturer. I encourage everyone to consider participating in a trial to help advance research on new and emerging pemphigus and pemphigoid treatments. While the short-term benefits help us now, the long-term benefits may change the lives of patients for years to come.

Chances are you have wondered why there are not more treatments available for pemphigus and pemphigoid, or at minimum, why there is not more research underway for these conditions. There are a few reasons for this, and unfortunately, it’s something that is not easily solved.

First and foremost, pemphigus and pemphigoid represent a rare group of conditions. A rare disease is also referred to as an orphan disease, and is defined as one that affects less than 200,000 Americans.  Drug companies typically spend money on research and development for diseases that affect a larger group of people.  In 1983, the Orphan Drug Act was passed.  This Act incentivizes research for treatments of rare diseases.  The three main incentives include federal funding grants to initiate clinical trials, tax credits of up to 50% and an exclusive right to market drugs for a period of seven years from FDA-approval date. Since 1983, many new medications were approved for existing diseases, and many existing medications were approved for new indications.

Studies on rare conditions like pemphigus and pemphigoid are challenging to get participation and potential subsequent FDA-approval for treatments for these conditions. P/P are rare, but additionally, most people with these conditions typically have had difficulties getting properly diagnosed and then the effective treatment for that diagnosis. When placebo is involved it means the chance of going without treatment which means the potential for relapse. Although rescue protocols for this are in place, it can still be scary to some people. Other challenges to recruitment into orphan drug trials include poor disease awareness and a small number of physicians who actually treat the condition. There also may be inclusion even when there is interest because people may have been treated already in a way that excludes them.

The IPPF has done a lot to try to work toward better enrollment in clinical trials by raising awareness among the specialists that would see people who have pemphigus and pemphigoid, and keeping a database of physicians who have at any time treated these conditions. As of October 20, 2015, there are 31 clinical trials in various phases for pemphigus and 30 for pemphigoid. Some involve non-drug research, others are for existing drugs to be approved for this indication and others are for drugs in development.

If you are interested in knowing more about these trials or would like to explore enrolling, talk with your physician and discuss this. You can also get more info and contact information on www.clinicaltrials.gov and take a look at the inclusion criteria and the participating centers.

What are Pemphigus and Pemphigoid
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