Tesamorelin Is Approved
This just in from the FDA:
The U.S. Food and Drug Administration today approved Egrifta (tesamorelin) to treat HIV patients with lipodystrophy, a condition in which excess fat develops in different areas of the body, most notably around the liver, stomach, and other abdominal organs. The condition is associated with many antiretroviral drugs used to treat HIV.
While that opening sentence says it's approved for "lipodystrophy," this term alone is of course an oversimplification. The drug, a growth-hormone releasing factor, actually is indicated for visceral lipohypertrophy.
In other words, big bellies.
Those of us of a certain age can remember the first time we saw this happen to our patients. Typical case would be a person with advanced AIDS starting a combination regimen in the mid1990s, usually involving indinavir (hence "Crix belly" or "protease paunch"). In the excitement about watching viral loads go down and -- more astonishingly -- CD4 cell counts go up, we initially could overlook the beach ball-sized and very firm mid-section protuberance that was growing larger with each visit. "I look like Big Bird," one of my patients memorably said. "Skinny legs, big gut."
But eventually we had to do something, which usually led to an imaging test to exclude a mass or some other badness. When the radiologists reported the test as "negative," we pressed them further -- at which time they'd note that the abdomen was filled with fat. Not subcutaneous fat -- in fact, the love handles and spare tires were usually absent -- but visceral fat, lots of it literally encasing the organs.
Many of those patients are still alive, and of course there hasn't been a whole lot we could offer them until now. And that's what tesamorelin is for -- treatment of HIV-related visceral fat accumulation.
(Quick aside: Isn't "tesamorelin" a beautiful word? It sounds like a cross between an exotic Middle Eastern spice and a fine fabric used for making high-end Italian suits.)
So the indications for tesamorelin sound straightforward. But here are a few of the many questions raised by the approval of this unusual drug:
- How can clinicians tell who has visceral fat accumulation vs. who is simply part of the Great American Obesity Epidemic? Sometimes it's obvious -- visceral fat you can't "pinch" -- but many patients will have both.
- Will tesamorelin be effective in reducing other problematic areas of fat accumulation? I'm thinking in particular of the massive neck and upper chest fat that really only can be managed with liposection, and even then it sometimes recurs.
- Will the patients who need the drug actually be willing to start a medication that requires a daily injection? Conversely, will some patients who don't need it ask for it anyway because they don't like the fact that middle-age hasn't been kind to their waistlines?
- Related: What's the off-label prescribing going to be like? One could envision a fairly sizable cash business from providers who specialize in cosmetic surgery and related interventions to reverse the aging process. After all, lots of the people who visit these clinicians are already paying out of pocket for the various services they seek -- what's one more line item on the bill?
- Related again: What is tesamorelin going to cost, and will insurance plans cover it? Remember, recombinant growth hormone -- which was approved for treatment of HIV-related wasting -- was extremely expensive, and notably was one of the few drugs not covered by even the most generous ADAP programs.
- How long will patients need to take it? It's fairly clear from the clinical trials that the beneficial effects in reducing visceral adiposity rapidly reverse when the drug is stopped. Will people be on it for a year? Five years? Life-long?
- Given that treatment will undoubtedly need to be prolonged, are there long-term benefits or safety issues that did not arise in the clinical trials? Does it reduce cardiovascular risk? Impair long-term glucose control? Have any effects on neoplastic or psychiatric diseases? To address safety, according to the company's press release, the FDA has mandated a long-term observational safety study as one of the provisions of the drug's approval.
Although I don't know the answers to the above questions, I do know one thing -- it sure is fun to say "tesamorelin."
That should count for something.
Paul Sax is Clinical Director of Infectious Diseases at Brigham and Women's Hospital. His blog HIV and ID Observations is part of Journal Watch, where he is Editor-in-Chief of Journal Watch AIDS Clinical Care.