Lymphedema news

A pill for lymphedema? Talking ubenimex’s potential with Dr. Quan of Eiger BioPharmaceuticals

A conversation with Dr. Joanne Quan, Chief Medical Officer at Eiger BioPharmaceuticals, about the ubenimex trial, the Stanford studies, and the important role patients play in the development of new therapies.

Living with lymphedema can be a real pill — but what if it could be treated with one?

Recent studies indicate it’s possible, and may even be a reality sooner than we think thanks to clinical trials of a drug called ubenimex.

Last summer I wrote about the ubenimex trials, which at the time of writing had just kicked off by dosing their first patient. The news generated a huge response from the lymphedema community — one of hope, excitement, and lots of curiosity — so I’m back with an update!

Photo courtesy Dr. Quan.

I recently had the incredible opportunity to speak with Dr. Joanne Quan, Chief Medical Officer at Eiger BioPharmaceuticals, a biopharmaceutical company focused on the research, development, and commercialization of therapies for orphan diseases; they are also sponsoring the ubenimex clinical trial.

Dr. Quan and I talked about the ubenimex trial, the Stanford studies, and the important role patients play in the development of new therapies… this is a long post, lymphies, but you’re gonna want to read it all. So get comfy and #StayElevated — lots of exciting info ahead!

The Stanford Studies

Before getting into the details of the clinical trial, it’s important to know a little about the research behind it.

“There’s been some really great research that’s been done at Stanford University by Dr. Stanley Rockson and Dr. Mark Nicolls, who have collaborated on this,” Dr. Quan said.

The research from Stanford University School of Medicine is really great: it not only reveals the molecular mechanism responsible for triggering lymphedema, but also presents a drug with the potential for inhibiting that process altogether.

Traditionally, lymphedema is regarded as a “plumbing problem,” where the buildup of lymph fluid is caused by a clog somewhere in the “pipes” of the lymphatic system. Although this is definitely part of it, the researchers at Stanford have discovered that the accumulation of lymph may actually be caused by inflammatory responses within the tissue of the skin.

Studying both animal models of lymphedema and humans with the disease, the researchers found a naturally occurring inflammatory substance called leukotriene B4 (LTB4) present in elevated amounts, and determined that these high levels were causing tissue inflammation and impaired lymphatic function.

Using mice that were given lymphedema, the researchers focused on finding a therapy that would directly address this biological process on a molecular level through pharmacological agents that would specifically target LTB4 production.

“What ubenimex does is decrease the levels of LTB4,” explained Dr. Quan. “And what they did was use this particular compound in the mice who were given lymphedema. They found that mice who got treated with the ubenimex actually had much improved lymphedema.”

Structural formula of ubenimex courtesy Wikimedia Commons.

The study’s findings, which were recently published in Science Translational Medicineindicate that researchers were able to induce lymphatic repair and reverse symptoms of the disease in mouse models of lymphedema by using ubenimex, which blocks the enzyme that generates LTB4.

“What we’re doing in the clinical study is to take the drug and see if it works in people,” Dr. Quan said. “As you can imagine, people are a bit different than mice, but I think we actually have some really good experimental evidence that suggests that this may work in people, and that’s why we’re doing this particular study.”

ULTRA Study

Logo courtesy EigerLE.com.

Ubenimex (also known as bestatin) has been used for decades in Japan to treat cancer with little to no side effects, and has been found to work well as an LTB4 inhibitor. It’s not approved for use in the United States, although it’s currently being tested as a treatment for secondary lymphedema in a clinical trial sponsored by Eiger BioPharmaceuticals known as ULTRA.

ULTRA stands for “Ubenimex in Adult Patients With Secondary Lymphedema of The Lower Limb: a Phase 2, RAndomized, Double-blind, Placebo-controlled Study of Efficacy, Safety, and Pharmacokinetics” and is exactly what its name says. (Although I see why they chose the acronym — much easier to remember!)

In the study, participants take their dose in capsule-form three times a day for 24 weeks. Then, around a month after the drug is stopped, there’s a safety follow-up. All-in-all, the total participation time is about an eight-and-a-half to nine month commitment.

The study is randomized and double-blind, meaning the patients are randomly assigned to receive either the active drug ubenimex or a placebo, and neither the patients nor the researchers know who’s taking what.

“We designed this particular study to give a really unbiased view of how the drug might be doing, and part of that is doing it blinded,” Dr. Quan said. “In the end, when all the patients are recruited and all complete the treatments — then we do what we call ‘unblind,’ and we essentially open the envelope and see who was on what.”

As a result of it being a blind study, the researchers won’t know if ubenimex works or not until after the study is completed and they review the data.

But what about primary?

Upon hearing about the study, many primary lymphedema patients — myself included — wondered if this would work for us, too, despite the trial focusing on patients with secondary.

“We chose to study secondary lymphedema of the lower legs really as an initial disease entity to study,” said Dr. Quan. “Obviously, if this works, then we have a lot of thoughts and plans to move forward into primary lymphedema, and also looking at lymphedema of the arm and other body parts, essentially.”

“The mechanism that this drug has is really fairly broad,” Dr. Quan reassured. “And so, potentially, it could work for lymphedema of many types.”

What this means for patients

“Ubenimex is in a capsule, so this would be different than any of the other therapies that are available for lymphedema,” Dr. Quan said. “I think that part’s potentially pretty attractive for lots of people who are already spending a fair amount of time and energy managing the other aspects of their lymphedema.”

The drug wouldn’t replace the need for regular lymphedema treatment, however, and the study is not claiming to be a standalone treatment.

“It’s still the early days,” Dr. Quan cautioned. “So we don’t know whether this works, and we don’t know whether this may work in people who aren’t using compression. Ideally, everyone should be doing manual lymphatic drainage, compression, you know — all those other things. And we want to see if this works on top of that.”

“Now, at some point it may make sense to see if we can replace some of those,” Dr. Quan continued. “But I think that’s a different type of study right now.”

Get involved!

Studies like these are a collaborative effort from both the professional side and the patient side, too. There’s not been a whole lot in the way of pharmaceutical interventions for lymphedema, so a study like this could really pave the way for other companies and treatments to follow.

“We’re sort of taking a bit of a leap entering into this space, but it’s best if we can do it as a collaborative effort with other members of the community,” Dr. Quan said. “I think, sometimes, people are a bit afraid of things that haven’t been done before. But I think here’s an opportunity for folks who see that there’s a need for something better to get involved.”

ULTRA is currently enrolling participants at four study sites: Stanford University in Stanford, California; The Ohio State University Wexner Medical Center James Cancer Hospital in Columbus, Ohio; Orlando Health, Inc., in Orlando, Florida; and Macquarie University Hospital in New South Wales, Australia.

If you’re interested in participating in the study, click here to visit the study’s websiteThere, you can learn more about ULTRA and take a study screener to see if you’re eligible to participate.

Pending the results of the current ULTRA study, Eiger is planning additional studies of ubenimex for lymphedema — so even if you aren’t eligible for the current study, you may be in the future!

Before you make the decision to participate in any clinical trial, though, it’s important to educate yourself first on what it means to participate so that you can make an informed decision — the NIH is a wonderful resource for this.

“I encourage people to think about it. Ask their doctors, talk to them, research about clinical trials and what it means to participate in one,” Dr. Quan said. “There are a lot of different things that folks who have lymphedema can do that may help develop other therapies as well.”

Final thoughts

“As a small company, Eiger has come to understand the unmet need here, and what a challenge it is for you and for other folks like you,” Dr. Quan said. “And so we’re stepping forward to say, ‘Hey, let’s just try to do something.'”

“There’s a number of steps and kind of a road ahead,” Dr. Quan said as we began wrapping up our call. “But we’re committed to taking that first step, and this is a collaborative effort with everyone within the lymphedema community.”

What do you think about a drug treatment for lymphedema? Would you take the pill? Let me know in the comments below!

I want to give a huge thank-you to Dr. Quan for taking the time to speak with me, as well as clinical program manager Erica McCluskey and senior director of clinical operations Tristen Moors at Eiger!

*Edited 05/16/2017 @ 9:15 AM to include study site locations.

45 comments on “A pill for lymphedema? Talking ubenimex’s potential with Dr. Quan of Eiger BioPharmaceuticals

  1. Reblogged this on My Lymph Node Transplant and commented:
    How exciting would it be if we could just take a pill to get rid of our Lymphedema… great research ..thanks Alexa for keeping us up to date

  2. Unless life threatening (chemo), I won’t use medications that are tested on non-human animals. It’s an outdated and unnecessary model that causes unnecessary suffering to the lab animals.

    • I can understand your position, Oedipa. It’s so important people participate in these clinical trials — I can’t wait to see what the results are once it’s completed!

      Wishing you the best,
      Alexa

  3. Thank you for keeping us updated!
    Let’s Do Something! Is the right track –
    Nothing ventured – Nothing gained!
    Fingers crossed, wishing in lucky stars, and prayer lines are working too! 😍👍🏻

    • Love your enthusiasm, Denise! I’ll be sure to continue updating on the study as it develops. I’m hopeful about this drug — I’ve got all my fingers and toes crossed (even my puffy lymphie ones!) ;)

  4. Aleda Knol

    I would love to think there may be a drug we could take to help our lymphedema suffering. I have a hard time not thinking that it is a plumbing problem, however, because if it is a systemic inflammation why does it only affect one of my arms (the one involved in lymph node removal due to breast cancer.). Would your whole body suffer from this inflammation then? Could I still take the drug even if my cancer has returned? So many questions. But this is exciting!

    • Hi, Aleda,

      You raise a lot of good questions! I agree with you – and I think the study acknowledges too – that there is that “plumbing problem” component, and that the inflammation is an issue that exacerbates an already compromised system. Full disclosure, though, that my medical background is as a patient (I majored in English in college! Haha) so I’m trying to understand it and learn best I can along with you! :)

      These would be great questions to email the organizers of the study (contact info here) for a more technical explanation, or even to present to your doctor for recommendations re: taking the drug if cancer were to return.

      Hopefully once the study is completed, we’ll get some clearer indications of whether it presents a successful treatment option. I’m really hopeful and excited about it right there along with ya!

      Be well,
      Alexa

  5. Effie Nave

    My daughter sent this information to me, it sounds wonderful, I would like to participate in this trial. I have been suffering with this for 13 years it has me great stress. Only another lymph patient would understand this annoying disease. Sincerely EFFIE NAVE

    • Hi, Effie,

      It does sound wonderful, doesn’t it? If you’re interested in participating, please visit https://www.eigerle.com for more information and to take a screening test to make sure you’re eligible. It would be amazing if this proves to be a successful treatment option for us — imagine all the people it would help! Hope for the future… :)

      Wishing you all the best,
      Alexa

  6. Diane Phillips RN, MSN/ED

    Exciting news! Love the fact that the trial is in the US and that Bestatin has been around for so long in other countries. Everything I read about the drug seems pretty safe. Tired of manual lymph drainage and compression stockings and pneumatic compression for a hour. Praying for all enrolled in the study and future research to find a break through to help simplify this life. Cancer was bad enough and now this constant reminder of a heavy leg. Fingers crossed this is the start to our cure!

  7. Hi,
    Thank you for going in-depth about what the drug is about as well as the study parameters. A piece that I found in this article that is worth to emphasize again is this … “The drug wouldn’t replace the need for regular lymphedema treatment, however, and the study is not claiming to be a standalone treatment.” I bring this forward, as we cannot ignore the other parts of the treatment (MLD, compression, exercise, nutrition, self-care, and lifestyle choices/factors) that also contribute to getting healthier and living better, even with lymphedema or lipedema.

    • Yes — I totally agree! I think it’s a common misconception that surgeries or pills will automatically “cure” lymphedema or negate the need for compression / MLD / etc. and that’s simply not the case, even though these interventions can be hugely beneficial in terms of reducing swelling and improving lymphatic flow. Until a cure is found, treatment is a multi-modal approach and should be practiced as such. We as patients must be proactive in our care, although I do acknowledge that it can be difficult for some due to physical limitations. A drug like ubenimex would make a great addition to the lymphedema treatment arsenal!

      Thank you for emphasizing an important point!

      Be well,
      Alexa

  8. Hi Alexa. This is exciting and I am so happy that more and more is being done on a international level. We all need to stick and fight together to make things happen! Have wanted to compliment you on your blog for some time ! Keep up the great work from one blogger to the other! Take care, Mo

    • Hi, Monica,

      Thank you for your kind words! It’s always great to meet a fellow lymphie blogger :) I’m right there with you about sticking together: international collaboration is where it’s at, from the patient level up to the medical professionals and researchers. It’s important to continue bringing attention to all the amazing work happening in the world of lymphatics, all the while supporting and uplifting our incredible community!

      Wishing you all the best!

      Be well,
      Alexa

  9. Thanks for this update and information. I’m so excited!

  10. This is wonderful and very exciting news, question: If someone hypothetically were to want to goto Japan to purchase some of this drug, what would be the best method? I assume it is a prescription medicine over there (it’s hard to find a lot of info), obviously insurance is out of the question, but anybody that is familiar with the Japanese health care system, steps to acquire the medicine and cost would be greatly appreciated.

    • Hi, Dave,

      I’m not familiar with health care systems in other countries, so I’m really not sure! Hopefully ubenimex or something similar will prove successful here, so we won’t need to go to such lengths for effective drug treatments… in the meantime, the clinical trial is still recruiting participants to test the drug! If you’re interested, check out http://www.eigerle.com for more info and to see if you qualify.

      Wishing you the best!
      Alexa

    • I live in Japan and just read this, will discuss with my lymphedema therapist tomorrow. Since this is a cancer drug I doubt it would be easy to get – and since I haven’t heard of any lymphedema use here in Japan, that would probably make it impossible. But the doctor who oversees the clinic should be in tomorrow so maybe I’ll ask him as well.

  11. alena ford

    This is so exciting. I have been leaving with primary lymphedema of my left leg since I was 19 years old. This is so frustrating knowing that there is no cure and you have to leave with it all your life. Only lymphedema patients will understand how uncomfortable and some days painful it is. Not even talking about dealing with clothing and shoes problem.
    I always search on the Internet the latest news of lymphedema cure and was getting devastated every time I find nothing new. Till yesterday. When I saw your article, I could not believe the title of possibility to cure lymphedema with drugs. I can not tell you how happy I am for myself and other people with this condition. This gives me a HOPE..something to look forward. I am super, super excited. Fingers crossed:)

    • Hi, Alena,

      It sounds like this news came to you at the right time! :) It’s so important for us to hold on to hope — and with researchers and scientists working to develop new treatments and a better understanding of the lymphatic system, there is lots to be hopeful for!

      I’m keeping my fingers crossed right along with ya!

      Wishing you the best,
      Alexa

  12. lorraine Pledger

    So hoping this therapy is effective!!! I have had lymphedema for only about year (post axillary lymph node clearance ) and already I am finding the management of it over whelming and the discomfort overbearing!! I don’t fulfill the eligibility criteria for the trial which is disappointing but if there is any potential that the drug works I would take it in a heart beat. I think there might be a queue of people trying to access the drug from Japan even before the phase 2 trials finish. Low side effect profile with 25 years history of usage, it seems to me, why wouldn’t you give it a go if there is any potential of it working?

  13. Peg De Rose

    Ubenimex AKA Bestatin aka simvastatin. Check side effects of all the different names for this drug before deciding to join the trial. Drug patents can be extended by finding new uses for an old drug. Makes money for the drug company to find a new use for an old drug but is it really an effective treatment for the lymphedema patient? Time will tell.

    • Hi, Peg,
      I agree — it is important to make an informed decision before participating in any clinical trial! However, Bestatin is not a statin drug.

      Be well,
      Alexa

  14. I just spoke with my lymphedema doctor in Japan, who was very aware of the study. She said it appears that it doesn’t work in all types of cases, but that when it does work, it seems to work quite well. Her impression was that the results will be presented at a conference late next year. And booo…. even if it’s approved in the US it’ll take several years more to be approved in Japan for lymphedema use.

  15. Natalie du Toit

    Wow!
    I bet this will take forever to get to South Africa, but it gives me hope!

    • Yip Im also wondering if we can obtain this drug and try it

      • Alena Ford

        The way i understood, this pill is not available as they r currently in phase of 2 of experimental study. FDA requirements are high before bringing a new drug on the market. But i hope they approve it soon because if it works we so need it.

  16. Alena Ford

    Hi everyone,
    I am currently considering to enroll into experimental study of ubenimex at university at Ohio.
    does anyone have any feedback about this study and if anyone considered to enroll?
    Thank you all and the best to all of us in finding the cure. Hope makes me feel better😉

  17. I’d love to get rid of this crappy afflictiction. I am cured of stage 3 ovarian cancer n having a pill to help us would be great.God Bless all who are paving the way 😊

  18. Excellent article that explains the trial. I am hoping to meet the criteria and be apart of the study. If I can help by participating, hopefully many others will benefit down the road.

  19. Thank you for highlighting this. My daughter diagnosed yesterday, so this gives me hope for the future.

  20. Gayle Burgess

    So very hopeful! Have considered the many surgical interventions but fearful of complications or further aggravation to a challenging situation. Have lived with Lymphedema over 50 years. At 11 was called a freak by a boy I had a crush on. Every spring when all the ladies are donning their cute shorts, sundresses, crops, I hide behind long, wide-legged pants; even 100 degrees you’ll find me hiding. The emotional trauma cannot be measured. The times lost to be able to engage with family – spontaneous walks on beach, walking from chaise to pool fearful of onlookers – cannot be measured. I do not mean to whine. I am very thankful to be able to walk, live mostly pain-free and be financially able to buy two pair of shoes to create one pair to wear (anyone size 7.5 with left foot bigger?). I am so excited at even the possibility of any improvement! Not sure where I fit in: primary and secondary is my condition. Figure if they can help me, they can help all! And that’s my prayer. While I have resigned my life to being lived out this way, I would love to see an opportunity for every person – especially the children – to have a normal life! Sign me up!

  21. I recently joined Instagram and discovered so many people with the same problem as myself, for many many years I have wished to find people with the same problem, this has been such a great support chatting with the girls, all of us trying to find our own cure’s.
    So to discover this new information gives so many of us hope, I’m saying my prayers that one day my life will be free of this disability and cruel disease…hearing the words there is no cure has been so consistent for years…thank You all for the continued research in helping us find a light at the end of a dark tunnel :)))))

  22. Pingback: Ubenimex (bestatin) treats lymphedema in mice. Will the drug help you?

  23. Margaret De Rose

    When I search Ubenimex I see it is also known as Bestatin. Bestatin was manufactured by Berlin Pharmaceutical Industry Co Ltd in Thailand and other pharmaceuticals as a generic for Simvastatin (Zocor). The statin class of medications and works by decreasing the manufacture of cholesterol by the liver and can have serious side effects. Please inform patients in the trial of the drug background and history. This is a new use for an old drug. It may help, it may have serious side effects.

    • Hi, Margaret,
      I agree that it’s important to research a drug and its history before participating in a clinical trial! However, despite the name drug name Bestatin, ubenimex is not a statin and does not belong to the statin class of medications.
      Be well,
      Alexa

      • alena ford

        Hi Alexa,
        do you have any latest news on when the trial will be ended and if FDA approves this drug?

  24. Hi, Alena,
    Great question! Eiger is hoping to complete entry into the study (enrollment) this year. ULTRA is a Phase 2 proof of concept study, meaning if the results are positive, additional studies with more patients would be required before FDA approval could be granted. So there’s still a little ways to go!
    Be well,
    Alexa

    • Alena Ford

      Hi Alexa,
      What were the results of phase 1 sunce this is phase 2 going? I was wondering how many patients reported improvement fron ubenimex.
      Thank you

      • The Phase 1 studies were done on healthy volunteers. This is the first time lymphedema patients have taken ubenimex – both the patients and doctors are blinded (which means neither know who is taking ubenimex and who is taking placebo), so the researchers won’t know if ubenimex works as a lymphedema treatment until after the very end when all phases of the study are completed and they review the data.

        In the end, once all the patients’ treatments have been completed, they “unblind” the study – as Dr. Quan explains in the interview above, it’s essentially like “opening the envelope and see who was on what.” Because the trial is still ongoing, they have not “unblinded” any of the Phases yet, so we won’t know the results for a bit!

        I am not affiliated with the study – just reporting on it! – so I hope that answered your question! :)

  25. 837 Brooke Lane, New Athens, IL 62264

    I have lymphedema in both legs and I have had at least 100 infections over 18 years. My docs are Washington University Physicians at Barnes-Jewish Hospital and Siteman Cancer Center in St. Louis, MO. Through the years they have watched over me always concerned for my lymphedema. In 1990 I had cancer that required radiation treatment. Within a few months I experienced the lyphedema infections. The only treatment I have had over those years has been wearing compression stockings, MLD therapy, antibiotics for the frequent infections. My left leg is more involved than the right leg, but I have also had the large red blotches on hips and stomach. I get very ill when being attacked with the infections. My left leg is so swollen there isn’t much definition between the ankle, calf, knee and thigh. I have never been offered a study. Depressing.

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