A Podcast Discussion With Daniel Berger, M.D.
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There were a couple of concerns. You had mentioned the minimal long-term risks of the drug. Those did come up a little bit during the FDA advisory committee meeting that met a couple of months prior to the approval of Egrifta. Although they did vote unanimously, it was 16 to nothing, that the drug should be approved, they did raise a couple of those potential long-term issues. Can you talk about them for just a moment?
Sure. There were some adverse effects that were observed during the studies, but in general, they seemed to be well tolerated and manageable. Patients taking Egrifta are more likely to get these effects because of how Egrifta works. It increases levels of insulin-like growth factor, or what's known as IGF-1. It's important to understand that some patients can experience events such as some joint aches, some mild swelling in their extremities such as their ankles, or get some mild stiffness in their joints, even some stiffness in their hands and feet, which I have found generally improves with some small exercises that tend to loosen the joints up. Some patients also had some injection-site reactions, some mild redness or tenderness at the injection site, which also clears up fairly quickly. It should be noted that there was a very small number of patients who appeared to have some allergic reactions such as one would expect -- the development of hives, etc.
But what you're referring to in terms of other concerns that came up at the FDA meeting, an important finding is that in the study, patients with mild diabetes did not show exacerbation of diabetes. But there were some small number of patients that experienced new diabetic symptoms. And in my opinion, this is a very small number.
It obviously is a concern. However, when looking at the total profile of the medication and the risks versus benefits, I believe that the committee felt that the benefits far outweighed the small number of patients that may have experienced new symptoms. And I believe that in terms of any other severe effects that would concern me, I'm not terribly concerned personally. I'm going to be monitoring my patients' blood sugars, as I believe other clinicians will be, especially people who are diabetic. From what I mentioned before, Egrifta's not really been studied in patients while on diabetes treatment, and this would be useful to investigate more closely, hopefully in phase 4, or post-marketing, studies.
There's also been a concern that because the mechanism for Egrifta increases IGF-1 levels, that being a growth factor, it may cause development of cancers. But there's been no evidence, at least with Egrifta treatment at present, of that occurring. But I think as patients use this more long term, it'll be very important to continue documenting and to continue monitoring our patients to learn more.
I think there was also something mentioned at some point during that advisory meeting about people developing antibodies to Egrifta and, as a result, having the drug become less effective over time.
Yes. Actually, in the studies, I believe somewhere around 50% of patients had developed IgG [immunoglobulin G] antibodies to Egrifta. However, despite that, most of the patients have continued to derive benefit.
There was a very small number of patients, I mentioned earlier, that had allergic reactions. And all those people that developed allergic reactions also had those antibodies to Egrifta. But it's not known whether the antibodies to Egrifta have any relevance to its efficacy.
Egrifta is the first drug that's been approved for this use: to treat any kind of fat gain, specifically in HIV-positive people, right?
Are there any other drugs out there, whether approved or in late development, that work similarly to Egrifta?
There have been a lot of medications that have been looked at to treat lipohypertrophy, or fat accumulation. But, as you say, currently there's been no other drug or medication that has ever been approved to treat visceral fat accumulation. So Egrifta is definitely the first.
In terms of what other things can be done for patients with fat accumulation: As I said earlier during this interview, certain antiviral agents can be metabolically unfriendly. Some studies have looked at switching therapy, in other words, switching to another effective regimen of medications. However, when these switch studies were done, the effects were modest and sometimes not consistent. Currently, we have the good fortune of having many new agents that were approved in recent years. And most of these therapies are felt to be patient-friendly treatment. So switching is now very limited use.
Other things, such as, for example, anabolic steroids were looked at. Low testosterone levels, for example, are seen in HIV-positive patients and are associated with visceral abdominal fat accumulation. But while we've sometimes used testosterone replacement in our patients, these individuals show increases in lean body mass or muscle tissue. It didn't really result in decreases in visceral abdominal fat in our patients.
Growth hormone, or Serostim, has been studied. Growth hormone resulted in significant decreases in visceral fat. However, Serostim did not get approved for use in this circumstance. And we believe that this is due to the severity of side effects that was associated with Serostim; that included significant development of diabetes, or changes that led to imbalance, or increased blood sugars.
Other treatments included other medications, such as some medications used to treat diabetes, like metformin. Metformin showed only a non-significant change. [Editor's note: "Non-significant" is a research term meaning that, although there was a change, it may simply have been due to chance.] Other diabetes medications, such as the insulin-sensitizing agents -- troglitazone, for example, was looked at, but that also didn't show significant improvement, and was eventually withdrawn from the market due to liver problems.
Other things that we try to do for our patients: One thing that I try to stress with my patients is that a change in diet can have some benefits. I've often advised my patients to reduce fat and some types of sugars, and begin with what's called a Mediterranean diet. Also, have smaller, more frequent meals as opposed to large meals. And combine this with exercise. Both diet and exercise have been independently shown to decrease abdominal visceral fat and improve lipids, such as cholesterol and triglycerides, and also benefit better glucose control.
All of this again leads to reduced cardiovascular risk, which I think is a big focus for our patients as they live longer now. But in terms of diet and exercise, it's sometimes difficult to get patients into the habit of making those kinds of changes.
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