By Martha Arnold
Before I retired, I worked in the pharmaceutical industry, helping drug development teams make their strongest case to the FDA for approval of their compounds across a broad range of therapeutic areas. Now as a person living with inclusion body myositis (IBM), I had been looking for opportunities to participate in a clinical trial, eager to “see it from the other side” as a participant rather than someone charged with interpreting the results.
When I heard about the Phase 2/3 trial of Abcuro’s ABC008 (now known as ulviprubart), I was all in. My decision to participate was easy to make, as I suspect it would be for most of us with IBM. We don’t have a well-recognized drug therapy and most of us (including me) don’t take any drugs for IBM. What do we have to lose? Being on placebo isn’t a major concern, as that would be the same nothing we currently have. And the earlier tests of the drug did not raise significant safety concerns.
My first task was to determine whether I would qualify. The listing of “Eligibility Criteria” on ClinicalTrials.gov very helpfully laid out the minimum requirements. There would be other inclusion and exclusion criteria, but what’s shown there was enough to get started.
- Sometimes, the criteria may seem arbitrary and restrictive. From my work experience, I know that criteria help ensure that enrollees can perform the activities—such as standing up from a chair—that are evaluated in the trial.
- Eligibility criteria have the additional role of establishing a relatively homogenous (similar) group of participants. This is important for the interpretation of the trial results. If the groups are similar, any differences seen between those getting the drug and those getting placebo can be seen as the drug’s effect, and not some other factor.
The second task: which of the trial sites might consider me? I knew that my chances would be better with an organization that had access to my records and where I had established relationships with providers over the years.
- For me, that meant the Myositis Center at Johns Hopkins University, where I had been followed since my diagnosis in 2014. But Hopkins was not listed as one of the first sites to be open for enrollment.
- With a total of 18 visits over 80 weeks, the site would need to be reasonably close to home. Honestly, we underestimated the time and burden of travel on me and my family. Still, I am retired, and the flexibility in my schedule should make it possible.
The third step: to make contact and find out if the sites that were convenient for me were considering new patients for enrollment. If so, what information would they need to see and how could my records be transferred? In my case, there was particular interest in my muscle biopsy, which is almost always necessary to confirm the diagnosis prior to enrollment in any IBM trial.
My profile seemed to fit the needs of the trial, and I was offered an appointment to begin screening at a trial site in Boston. It took several visits to complete the tests and confirm that I qualified. These early visits also educated me about what to expect: the time and activity commitments I would be making, what was known so far about the drug’s effect, and what side effects I might expect.
- Screening is a bit of a black box, involving a lot of blood tests (15 tubes!), a physical exam, an in-depth review of my health status, and some less formal evaluations. Was I able to perform the necessary muscle tests consistently? Was there anything in my health history (like cancer or severe arthritis) that could interfere with the trial? Was I likely to be a reliable participant in the trial? (Missed appointments lead to gaps in the data, which can make the results less reliable.)
All aligned for me, and I was invited to enroll. At my initial visit, I signed the informed consent, repeated many of the screening activities to establish a baseline, and received my first dose of test medication. I was on my way for the 80-week study entitled “Randomized, Double-blind, Placebo-controlled, Multicenter Trial to Determine the Efficacy and Safety of ABC008 in the Treatment of Subjects with Inclusion Body Myositis.”
After an initial flurry of visits, I settled into traveling to the clinic every eight weeks, where multiple tubes of blood were drawn, various tests were performed, and I received a dose of the test medication. A study nurse administered it by an injection under the skin in my abdomen. It may have been placebo, or a low dose (0.5 mg/kg) or a high dose (2.0 mg/kg) of ulviprubart. This was a “blinded study,” which means no one knows whether I received drug or placebo. (Not me, the doctor, study nurse, pharmacist who prepared the dose, nor anyone at the company know what my injections contained.)
At the end of the trial, I was offered enrollment in an “open label” follow on study, which means everyone knows that we are receiving the drug at the highest dose: 2.0 mg/kg body weight.
- I had both hoped and expected that the company would offer such a trial. The purpose of this type of trial is to learn what happens as patients stay on the product for longer periods of time, perhaps even several years. Do new side effects emerge? Does the product seem to maintain its effect over time?
- People ask me whether this second study is being done because the first study showed evidence of efficacy. It’s important to note that no one knows the results of the double-blind trial. That answer won’t come until the final patient in the initial study completes their final study visit. All of the data from all of the 250 or so patients would then be entered in the database. There’s a disciplined, lengthy process by which the data is checked for accuracy and completeness before the database can be “locked.” Only then can the patient data be sorted into groups by who received drug and at what dosage and who received placebo to allow the effect of the drug to be compared to placebo.
I am frequently asked is ulviprubart helping? My honest answer is, I don’t know. I feel as if my disease progression is slow, but it always has been slow. Based on what I have learned about the medication, I don’t expect to regain the strength I’ve lost as it does not rebuild muscle. What is does do is deplete (remove) a particular type of T cell that is believed to be involved in IBM. Based on a report presented at the American Academy of Neurology meeting, it does that very well.
The real question is, does depletion of the problem T cells matter? More specifically, does ulviprubart affect the progression of IBM?
- To obtain regulatory approval, the drug needs to show in a clinical trial that it changes how patients feel, function, or survive. The hope is that the first study will show that ulviprubart slows, or perhaps even stabilizes disease progression as measured by the IBM Functional Rating Scale (IBM-FRS) and that this change is different from what is seen with placebo.
As we all know, it’s difficult to measure disease progression with precision, and while the IBM FRS is the primary endpoint, additional data from other types of tests are being collected to help understand other effects of the drug. These other tests include MMT (manual muscle testing), TUG (Timed Up and Go: how long does it take the patient to get up from a chair, walk three yards, and return to the starting position), strength measurements of fingers and legs using dynamometers, and several PROMs (Patient Reported Outcomes Measures: questionnaires filled out by patients.)
When will we know? We understand that the initial read of the primary endpoint of the placebo-controlled trial is currently planned for first quarter 2026. Until then, all of us living with IBM are eagerly awaiting the results.
Martha Arnold is a former member of TMA’s Board of Directors. She has a background in marketing and regulatory communications within the pharmaceutical industry. Martha was diagnosed with inclusion body myositis in November 2014. She lives in Pennsylvania with her husband Mark.
A version of this article was published in the Summer 2025 issue of The Outlook magazine.