Informative Questions and Answers at TheBody.com

Gynecomastia problems: http://www.thebody.com/Forums/AIDS/Aging/Q223555.html

Shingles Vaccine for HIV+ People:
http://www.thebody.com/Forums/AIDS/Aging/Q222619.html

Recently Diagnosed with HIV:
http://www.thebody.com/Forums/AIDS/Nutrition/Q223309.html

Taking Egrifta and Gaining Weight:
http://www.thebody.com/Forums/AIDS/Nutrition/Q223414.html

How Do I Improve my Sperm Count?
http://www.thebody.com/Forums/AIDS/Nutrition/Q223473.html

Wormwood and HIV
http://www.thebody.com/Forums/AIDS/Nutrition/Q223420.html

Parotid Gland Inflammation and HIV
http://www.thebody.com/Forums/AIDS/Nutrition/Q221140.html

Winstrol (Anabolic Steroid) and HIV Medications
http://www.thebody.com/Forums/AIDS/Nutrition/Q220965.html

Other Options for Lipodystrophy Besides Egrifta
http://www.thebody.com/Forums/AIDS/Nutrition/Q221875.html

How to Gain Muscle
http://www.thebody.com/Forums/AIDS/Nutrition/Q217583.html

PoWeR Resources

I wanted to remind everyone about resources from Program for Wellness Restoration (PoWeR).

Regards,


Nelson Vergel

Director

Sites:

http://www.powerusa.org/

http://www.facialwasting.org/

http://www.testosteronewisdom.com/

http://www.agingwithhiv.org/

http://www.salvagetherapies.org/

Groups:

https://www.facebook.com/groups/testosteronereplacement/ 

http://health.groups.yahoo.com/group/PozHealth/ 

https://www.facebook.com/groups/egrifta/

https://www.facebook.com/HIVCure 

https://www.facebook.com/PoWeRUSA 

Ask questions:

http://www.thebody.com/Forums/AIDS/Aging/ask.html 


Twitter: 


https://twitter.com/#!/nelsonvergel

Doctor's Lists, Directories, Compounding pharmacy, etc:
http://powerusa.org/resources.html

Upcoming:

ShortcuttoShape.com

Diabetic Retinopathy in HIV Subjects Treated With EGRIFTA®

This is a study required by the FDA to determine if Egrifta use in HIV+ people with diabetes can increase the risks of diabetic retinopathy.


http://clinicaltrials.gov/ct2/show/NCT01591902

Diabetic retinopathy  is a complication of diabetes that affects the eyes. It's caused by damage to the blood vessels of the light-sensitive tissue at the back of the eye (retina).

At first, diabetic retinopathy may cause no symptoms or only mild vision problems. Eventually, however, diabetic retinopathy can result in blindness.

Diabetic retinopathy can develop in anyone who has type 1 diabetes or type 2 diabetes. The longer someone has diabetes, and the less controlled your blood sugar is, the more likely you are to develop diabetic retinopathy.

To protect their vision, patients with diabetes should take prevention seriously. Patients should carefully controlling their blood sugar level and scheduling yearly eye exams.

Previous studies have show that the use of growth hormone contributes to the development of diabetic retinopathy in humans. (http://care.diabetesjournals.org/content/17/6/531 )

Egrifta is a growth hormone releasing hormone, hence the concern from the FDA.

EGRIFTA® is an FDA-approved treatment for the reduction of excess abdominal fat in HIV-infected patients with lipodystrophy.


More information on Egrifta on Egrifta.com

New treatments for HIV associated lipodystrophy beyond Egrifta

Question from a person living with HIV:
May 2, 2012

I body build and work out, eat right, etc. The lipodystrophy I accumulated during my early use of Crixivan and others doesn't really go away that much. It's frustrating, depressing.

I do also appear to have some features of "muscle belly" where there is a space between my lower abs (possibly caused by strain). I've read about adbominoplasty.

Apart from egrifta, which my ID doc does not recommend, what other options are there now or on the horizon?

I want to get a CT scan of my gut to see just how pervasive it is. But to my knowledge, it's not just easy to go in to the organ area and remove the omentum, etc. That's all very risky.

Over the years I've gotten very depressed about it, even to the verge of eating disorders. I have 2 closets full of nice shirts that I can't/wont wear, as my gut protrudes. I'm otherwise very in shape and muscular.

What can I do? Is there any hope for this problem...

Answer from Nelson: New treatments for lipodystrophy beyond Egrifta

Are there any options for HIV+ patients who cannot get Egrifta to treat their belly fat?

From : http://www.thebody.com/Forums/AIDS/Nutrition/Q217585.html?ic=700101

Anything Available for Those of us who cannot get Egrita? Oct 4, 2011 Nelson, my insurance company refuses to pay for Egrifta after my doctor wrote a letter. I have a lot of visceral fat (18 pound increase in weight since I started HIV treatment). Is there any other option for me? I have a good job but cannot afford the $2000 per month cost of Egrifta.
		Response from Mr. Vergel I am sorry that you have had such trouble trying to access Egrifta(Tesamorelin)which is indicated for the reduction of excess abdominal fat in HIV-infected patients with lipodystrophy. Egrifta is a growth hormone releasing hormone that makes your own pituitary gland release physiologic levels of growth hormone. Prior studies using growth hormone (Serostim) showed that visceral fat was effectively decreased by growth hormone, but GH caused side effects that made the FDA reject Serono's application for lipodystrophy for Serostim. So Serono bought the rights of Tesamorelin from a Canadian company (Theracnologies) after it was shown that their growth hormone releasing hormone did not have the same concerning side effects (hypergylcemia, joint aches, edema, and others) that Serostim had. Egrifta got approved by the FDA but the FDA also required the company to engage in post approval studies to prove that the hormone did not increase incidence of cancer, since there is some fear that growth hormone products can do so. I know that Serono is making progress trying to get the product included in different formularies around the country, but there are still insurance companies and Medicare Part D programs that are not paying for it. And sometimes it is difficult for physicians to spend the extra time required to write letters of necessity to try to fight insurance companies. Some Medicare Part D patients who are lucky enough to get the product paid for cannot afford the high copays of over $100 per month, so there are still challenges in access even for those with third party coverage (there is copay assistance for non Medicare patients, though). Hopefully that will get better with time. For those patients with no insurance, Serono has set up a very good compassionate access program to cover the cost of the hormone for those with incomes under $60,000 a year. More on Egrifta.com I remind people that this hormone requires daily injections under the skin. The average visceral fat loss in the studies was around 17%, but when Theratecnologies (the manufacturer) separated responders versus non responders they found out that 30 % of all patients did not respond at all to the injections (their fat did not decrease). But the rest who responded, the fat reductions were as high as 27%. The manufacturer did not control for those who exercised or went on a special diet, however. So, we do not know if patients who responded best were also using other modalities that may have improved that response. As it stands, Serono and Theratecnologies have no idea how to predict who will respond to the daily injections. Also, do not forget that the fat lost will come back if you stop the product, although no one has done a study to see what happens to those patients who made permanent and durable life style modifications through the use of Egrifta. Those patients may retain some of the benefits even after drug cessation, but that is just my opinion. There is a generic option of a growth hormone releasing hormone that acts in the same way as Egrifta but it is a peptide with a shorter molecule chain. It can only be obtained by prescription from a compounding pharmacy. It is called Sermorelin Acetate. Like Egrifta, it stimulates the pituitary gland to naturally produce increased amounts of human growth hormone. The increased volume of human growth hormone produced by the pituitary gland causes an increase in the production of Insulin-Like Growth Factor-1 (IGF-1) by the liver. Increased IGF-1 has been associated with increased lean body mass and decrease fat but as I said before, some skeptics fear that it may also increase growth of malignancies (this is unproven). Sermorelin can cost anywhere from $300-$500 a month depending on the dose used. And insurance companies will not pay for it, so you will have to pay out of your own pocket. Most doctors do not know about this option, however. Like with any option to improve body composition, you should make sure that your thyroid and testosterone hormone levels are OK since that will ensure that your response will not be impaired by deficiencies of both hormones. Resistance/cardiovascular exercise and high fiber-low sugar-high protein diet are also two life style habits that will probably enhance response, although we really do not have controlled data on this combination that intuitively makes sense. You can find a compounding pharmacy close to you at : Compounding pharmacies Depending on the state that you live in, most compounding pharmacies deliver by mail to your home. The price differential among pharmacies is big, so call around. I and a lot of my pozhealth group members have been usingapsmeds for a few years for cheaper testosterone, nandrolone, HCG and other products like Sermorelin. Please let me know if you have any more questions. This is an emerging area that has been of great interest in the community, but one that has lost a lot of funding even as we grow older with HIV and need more data on therapies that can help us live healthier and stronger. Nelson Vergel

Nelson's Top 10 Tricks for Fat Loss

By Nelson Vergel

June 28, 2011

1. Get real. Ask yourself: What is getting in the way of my health? What excuses am I using to not start giving a damn? There is no perfect time to start. Do it now, even if it means one change per week in your lifestyle choices. You deserve to feel and look the best you can!
2. You cannot change what you do not measure!
   • Download a step counter (pedometer) app to your phone or buy one to carry with you all day. Research has shown that 10,000 steps a day keep people from gaining weight and may help those wanting to lose weight. It approximately equates to 3 miles. If by 6 pm you have not reached that goal, you can make up for the difference on a treadmill, walking the dog, walking to the store, etc. Read more on this.
   • Weigh yourself 3 times a week in the morning while on an empty stomach.
   • Get yourself a ring to wear on one of your fingers, or use the one you are wearing now; it's the best way to find out if you are inflamed or holding too much water. When tighter, you need to exercise to decrease inflammation and water retention.
   • If you have a progressive doctor who can refer you for a full DEXA body scan, good for you. This is the best way to know your body composition in every part of your body.
3. Change the way you drink and eat:
   • Avoid drinking sodas, fruit juices (eat fruit instead), more than two glasses of wine a day. Carry a water container in your car, office, and any place you hang out, and sip from it all day (you can add flavored Benefiber or Citrucell to that water if you need to drink something with flavor).
   • Also, avoid eating sweets, white bread, bagels, muffins, and most cereals (they are loaded with sugar and high-fructose corn syrup). Instead eat whole grain, dark-colored bread (if you have to), and never consume carbohydrates by themselves (adding good fats and fiber to carbs slows down glucose and insulin spikes in the blood that may predispose you to metabolic syndrome and fat gain). Watch a great lecture that will open your eyes to the effect of sugar on health.
   • Consume 20 grams of fiber (soluble and insoluble) per day. For most of us, this is hard to do unless we eat beans, nuts, and 4 servings of fruit and vegetables. Fiber improves insulin sensitivity, makes you feel full longer, keeps your gut healthy (friendly gut bacteria that produce vitamins love fiber), keeps you regular, and can lower the chances of getting colon cancer. Buy Citrucell or Benefiber, two over-the-counter products available in most grocery stores. Try to consume 12 grams of fiber a day from these supplements in water. You can also add them to soups, oatmeal, scrambled eggs, yogurt, water to sip all day at work, sauces, and home-made salad dressing.
   • To ensure that you have enough fruits and vegetables at home, buy frozen ones (frozen fruits and vegetables tend to be cheaper and loaded with vitamins since they are picked at their prime).
   • Follow a slow carb (low glycemic index) diet. Read this article carefully!
   • Twice a day, snack on almonds, pistachios, walnuts, and other nuts at work to get your good fats and fiber, and to make you less likely to cheat later. If you get tired of their taste, mix them with some dried fruit. Research has shown that people who eat nuts tend to have lower LDL cholesterol.
   • Avoid junk and fast food. The best way to do this is to have enough food at home and to bring lunch to work. Cook a lot of food on weekends and freeze meals in small containers you can take to work or heat up at home. Get yourself a slow cooker and use its enclosed cookbook to prepare warm foods that you can come home to. Do not sabotage yourself by bringing sweets and junk into your home. If you do, you'll eventually eat them (most of the time, in one sitting!).
   • Watch your cravings at night, when most people find it the most difficult to avoid overdrinking alcohol or eating ice cream, cookies, and comfort foods.
   • Eat a large breakfast, a moderate lunch, and a small dinner. I know this sounds completely different to what most of us are doing every day.
   1. Skipping breakfast makes you more prone to overcompensate by eating more calories late in the day. Your body has spent 7-8 hours without food and is starved for nutrients in the morning. Do not feed it sugar and white flour products at this important time, like many people are accustomed to doing due to being rushed. Eggs, oatmeal (the type that has no added sugar, and you can add whey protein powder to it!), Greek-style yogurt with nuts and fiber supplements, low-fat cottage cheese with fruit (if you're not lactose intolerant), almond butter sandwiches on multigrain (high-fiber) bread, and fruit are all good choices for breakfast.
   2. For lunch have some soup and a glass of water first and wait 10 minutes to trick your body into feeling full faster. Grilled chicken with vegetables, tuna salad over greens and nuts, a Greek salad with sliced steak, and any Mediterranean food choices are good.
   3. For dinner, fill yourself with stir fried (use olive oil!) vegetables and lean meats. Two hours before bed, you can have half an almond butter sandwich or yogurt with fruit. You will not be hungry and desperate with this diet!
4. Do resistance exercise with machines at the gym if you are a beginner, or weights if you have more experience. Here are some other exercise recommendations.
5. Get your hormones checked and supplemented if low
   • If you are having a hard time losing weight and you are doing all of the above, have your doctor check your blood levels of free testosterone and thyroid hormones (TSH, T3 and T4) (yes, women and men!). Low hormone blood levels can impair fat loss and energy levels required to exercise. They can also make your less prone to be motivated to follow a healthy regimen. Readmore about testosterone here.
6. If you have access to a glucose tolerance test, take it. This test will determine how your body uses glucose for energy and compare it to a normal response. If you have impaired glucose tolerance, your doctor may want to prescribe metformin, an insulin sensitizer that may help people lose fat by helping their insulin work better at controlling blood sugar and metabolism.
7. If your belly is hard and you cannot pinch much fat, you may mostly have visceral fat. You may want to talk to your doctor about a new FDA-approved product for HIV-associated visceral fat calledEgrifta (tesamorelin). Egrifta is a growth hormone-releasing factor that makes your pituitary gland make your own growth hormone. Growth hormone has been shown to help burn fat. If you do not have insurance, you can apply for patient assistance (more on Egrifta.com).
8. Drinking a tablespoon of apple cider vinegar before every meal has been shown to improve glucose tolerance and insulin response. Better glucose tolerance and lower insulin resistance can make it easier to lose fat. Read more on this.
9. Supplements:
   • Be careful with weight loss supplements since they are loaded with caffeine and stimulants that can raise your heart rate and blood pressure.
   • Take a multivitamin after breakfast and lunch.
   • Take Carnitine, 1,000 mg with breakfast and 1,000 mg with lunch; here's a study on Carnitine.
10. Find a support system that is there for you through all of your new lifestyle changes. Having an exercise/diet buddy is the best way to improve adherence to your diet and exercise program. Join groups online. Surround yourself with friends who support you all the way and enable you to succeed!

Send Nelson an e-mail.

EGRIFTA, Erasing The Scarlet Letter Of HIV- By Tony Adams

http://www.southfloridagaynews.com/sfgn-columnists/columnists/tony-adams-column/3234-title-egrifta-erasing-the-scarlet-letter-of-hiv.html

Update on Egrifta for the reduction of visceral fat accumulation associated with HIV lpodystrophy

Serono launched Egrifta this month.

Doctors are calling in the number included in the link below to get the paper work started for insurance reimbursement.

It seems that some insurance companies are  already starting to pay for it, but high copays may be required. Serono has a $200 copay assistance per prescription.

The total yearly cost is $23,900.   It is injected once a day under the skin (2 mg).  After 26 weeks, some people lose anywhere from 15 to 25 % (avg 18%). You will regain the fat if you stop using i.

I encouraged Serono to fund studies with exercise and the use of Metformin, two approaches that may enhance fat loss.

They could not tell me if any Medicare Part D program has already paid for drug yet.  There is no copay assistance for Medicare Part D patients due to a federal law that prohibits them.

The patient assistance program provides free drug to people with incomes lower than 6 times the poverty level ( around $68,000 per year for a single person with no dependents). Your doctor has to contact them, per the following link:

http://www.thebody.com/content/art60271.html?ic=700100

I encourage that people on this list try to apply for the patient assistance program. The Fair Pricing Coalition ( a group of activists that I am part of) needs to find out if there are any problems in applying for this program, so please help us audit it and report to this list.

More info in Egrifta.com

Egrifta Gets Approved for the Treatment of Abdominal Fat Accumulation in HIV- Activists Ask Serono to Price it Affordably

Fat busting, but at what cost?: http://blogs.poz.com/tim/archives/2010/11/fat_busting_but_at_w.html 




Press Release from Serono:

http://multivu.prnewswire.com/mnr/emdserono/47019/


Here's a link to the full prescribing info via Serono's website:

http://www.emdserono.com/cmg.emdserono_us/en/images/FULL%20PRESCRIBING%20INFORMATION_tcm115_59676.pdf?Version=


A Closer Look at Egrifta, a Newly Approved Treatment for HIV-Associated Belly Fat Gain (Lipohypertrophy)

http://www.thebody.com/content/art59340.html

For physicians interested in learning more about EGRIFTA™ and
the process for prescribing EGRIFTA™, call the AXIS Center
toll-free at 877-714-AXIS (2947).


Egrifta.com will have more information soon about patient assistance and other important issues

Briefing Information for the May 27, 2010 Meeting of the Endocrinologic and Metabolic Drugs Advisory Committee

http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/EndocrinologicandMetabolicDrugsAdvisoryCommittee/UCM213260.pdf



LETTER SENT BY ACTIVISTS TO SERONO:

David L. Stern
Executive Vice President
Endocrinology
EMD Serono Inc.
Rockland, MA

Dear David,

Thank you for taking the time to meet with the Fair Pricing Coalition (FPC) on August 9, 2010 regarding the pricing of Egrifta (tesamorelin). We believe that Egrifta, if approved, will be beneficial to many people with HIV-associated lipohypertrophy by improving their self-image, quality of life and adherence to their HIV treatment regimens. However, Egrifta only has a minimal effect on fat deposition with only modest waist circumference changes described.  Further, there is no accompanying mortality data that might convince patients and providers Egrifta was actually worth an exorbitant price.  Moreover, unlike Serostim, Egrifta must be used continuously to retain any effect.  This means continuous drug costs and continuous profits.  Surely, the ultimate price of the drug should be considered in light of these circumstances.

It is for these reasons that we feel strongly that Egrifta must be priced reasonably and affordably to allow the widest access possible for the greatest number of people. While we understand and appreciate the pricing considerations that EMD Serono put forth at the meeting, we also know that the reaction to the final price by patients and their advocates, as well as payers and providers must be favorable in order for this drug to widely accepted, desired by patients and covered by payers.  Moreover, Egrifta is the first drug of its kind for hypertrophy.  Thus, any drugs that follow Egrifta will undoubtedly be priced higher than Egrifta, resulting in a continued upward spiral of drug costs that are healthcare system cannot absorb.

We hope that EMD Serono will consider the concerns we raised at the meeting before determining the final price of Egrifta. As we stated at the meeting, we hope to be able to support the use of Egrifta and your pricing decision.  We will do so only if we believe Egrifta it is priced within a reasonable range.

We look forward to continued dialogue on this matter and hope it will not be necessary to publicly denounce EMD Serono and the final price of Egrifta .

If you have any questions or concerns, please do not hesitate to contact me by phone or e-mail.

Very truly yours,

Jeff Berry

Fair Pricing Coalition

AIDS Activists Support the Approval of Egrifta- But With Some Conditions for Theratecnologies and Serono

17 May 2010

Paul Tran, BS Pharrn, RPh Advisors and Consultants Staff Center for Drug Evaluation and Research Food and Drug Administration 5630 Fishers Lane, HFD-21 Rockville, MD 20857

Dear Mr. Tran:

On behalf ofthe Drug Development Committee (DDC) ofthe AIDS Treatment Activists Coalition (ATAC), I am writing to urge members ofthe Endocrinologic and Metabolic Drugs Advisory Committee (EMDAC) to recommend approval of Egrifta (tesamorelin) for the treatment of HIV-associated lipohypertrophy (NDA 22-505). This letter of support is submitted free of influence, financial or otherwise, from the NDA's sponsor, Theratechnologies, or Egrifta's planned U.S. distributor, EMD Serono.

Though the exact prevalence of lipohypertrophy among HIV -positive patients is not well established-the prevalence of the broader lipodystrophy syndrome is believed to be between 18 and 81 percent of people living with HIV-it has been an established comorbidity in the HIV patient population since the mid-1990s. Indeed, it is one of the only clinically significant HIV-related manifestations for which there is no proven treatment modality approved for use.

After review of the published data, we firmly believe that Egrifta, with its moderate efficacy profile and minimal adverse effects, should receive an EMDAC approval recommendation and cleared for marketing by the Food and Drug Administration (FDA). However, we remain sensitive to the fact that there are lingering concerns and questions regarding Egrifta's long-term efficacy and safety. Thus, our support for approval hinges on the establishment of post-marketing safety and efficacy features, clearly written into the product's labeling, along with a commitment to conduct additional safety and efficacy evaluations.

ATAC. 611 Broadway, #308 . New York, NY 10012.646/284-3801. admin@atac-usa.org

Page 1

Interpretation of Efficacy Evaluations

Our initial optimism began with the successful completion of seven Phase II studies showing clear benefits-with minimal adverse events, notably a statistically significant increase in rates of glucose intolerance and diabetes mellitus-associated with 2 mg daily dosing of Egrifta.

The 26- and 52-week efficacy data from Theratechnologies' two Phase III studies, LIPO-Ol0 and CTR-l0lljCTR-l012, solidify our encouragement. The 15 percent and 11 percent reductions in visceral adipose tissue (VAT), respectively, after 26 weeks (and maintained reductions among patients treated for 52 weeks) and the differences in the intent-to-treat and per-protocol analyses with respect to the primary endpoint (a VAT reduction of ~8 percent) are proof-positive of Egrifta's potential for HIV-infected patients with lipohypertrophy. We are also heartened by Egrifta's secondary benefits, compared with placebo, including decreases in waist circumference, increases in lean body mass, preservation of subcutaneous adipose tissue (SAT) and significant improvements in triglyceride levels and other CVD-related biochemical indices.

It is disappointing that the Phase III studies lacked the design and resources needed to validate decreases in VAT as a surrogate marker for reduced cardiovascular disease (CVD) risk, in light of data indicating that VAT and increased waist circumference is a predictor of clinical and subclinical CVD in both HIV-positive and HIV-negative individuals. There is undoubtedly a need for observational and randomized, controlled studies exploring the effects of VAT -reducing agents, including Egrifta, on the absolute and relative risks of serious cardiovascular and cerebrovascular events, as well as other clinical manifestations such as sleep apnea and pancreatic, liver, pulmonary and vascular functioning.

There is, however, much to be said for patient reported outcomes of both studies. These data cannot be overstated given the disfiguring and stigmatizing effects of lipodystrophy. Increases in VAT have clearly been shown to be associated with psychological distress, impaired quality of life measurements, reduced willingness to commence antiretroviral (ARV) therapy and poorer adherence among those on ARV treatment.

As is clearly documented in the published data, Egrifta treatment is associated with significant improvements in patient ratings of belly and body appearance distress, along with improvements in physician ratings of belly profile. These comprehensive data are unmatched by any other lipohypertrophy-reversing strategy explored thus far.

ATAC. 611 Broadway, #308 . New York, NY 10012.646/284-3801. admin@atac-usa.org

Page 2

Interpretation of Safety Evaluations

Unlike the last hormonal agent (Serostim; recombinant human growth hormone) reviewed and ultimately rejected by the FDA for the treatment of lipohypertrophy, the 52-week data from Egrifta's two Phase III studies are encouraging with respect to safety. Indeed, they establish that Egrifta's moderate efficacy outweighs Egrifta's minimal adverse effects.

Rates of injection site reactions, including localized hypersensitivity, appear to be more common among Egrifta-treated patients compared with placebo recipients. These rates, however, are dwarfed by those associated with another injectable agent, Fuzeon (enfuvirtide), used by people living with HIV.

While there also appeared to be slightly larger rates of growth hormone-related adverse events, such as arthralgia and edema, among patients receiving Egrifta compared with placebo, the reported percentages do not compare with the high rates of growth hormone­related events seen in Phase III clinical trials of Serostim.

Phase II and Phase III studies have consistently documented that Egrifta has an extremely limited effect on glycemic measures and did not appear to significantly increase the risk of glucose intolerance or diabetes mellitus. In fact, as is documented in the available data, patients with diet-controlled diabetes can receive Egrifta without an increased risk of untoward effects. Though an increased risk of glucose intolerance or diabetes cannot be ruled out completely and should be studied further, the risk-at least over 52 weeks of treatment-is minimal when balanced against the drug's moderate efficacy.

Egrifta's highly variable effect on insulin-like growth factor 1 (IGF-l) in a significant number of patents is not without potential concern. While we understand that these variations have not been associated with any clinically meaningful adverse effects, we believe that additional, long-term data are necessary to confirm these initial findings.

Another concern is the development of anti-tesamorelin IgG antibodies in a sizeable number of study participants. Though we are aware of data concluding that antibody production to this peptide is not associated with any clinically meaningful decreases in efficacy or increased rates of adverse events, we have not yet seen research exploring whether anti-tesamorelin IgG antibodies have an effect on endogenous growth hormone production after drug cessation. We are also unaware of data exploring the potential of these antibodies to shunt treatment responses to Egrifta in the event the drug is stopped and then restarted. These data, if not already compiled and analyzed, are necessary.

As with virtually every agent that has been considered by the FDA for an HIV indication, we are not without concerns regarding the long-terms safety of Egrifta. Knowing that the drug

ATAC. 611 Broadway, #308 . New York, NY 10012.646/284-3801. admin@atac-usa.org

Page 3

will need to be continued-perhaps indefinitely-to maintain reductions in VAT, we firmly believe that the product's labeling should feature prominent safety-related instructions for clinicians and patients, notably the need for regular glycemic and IGF -1 testing, along with cancer screenings, with recommendations to terminate Egrifta therapy when appropriate.

We also believe that a recommendation for Egrifta's approval be met with a commitment from the sponsor to conduct a long-term post-marketing study-either observational or randomized in design, following patients for at least three to four years-to collect data regarding the long-term safety of Egrifta.

Further Recommendations

In addition to our request for long-term safety data via a post-marketing study, we advocate for the following:

1)     Phase IV evaluations of Egrifta-associated VAT reductions on the risk of CVD. Though Theratechnologies should not be required to evaluate Egrifta in studies employing myocardial infarction or ischemic stroke as endpoints as a condition for approval, we believe that post-marketing studies exploring associations between VAT reductions and softer measures ofCVD-such as vascular function-should be required.

2)     Required Phase IV studies exploring the effects of Egrifta-associated VAT reductions on other clinical outcomes, including fatigue, gallbladder disease, liver disease, osteoarthritis, pulmonary function and sleep apnea.

3)     Required Phase IV studies exploring Egrifta in combination with exercise and/or diet modification to determine if VAT can be synergistically decreased.

4)     A required Phase IV gender-balanced clinical trial evaluating the safety and efficacy of Egrifta in HIV-positive women with lipohypertrophy compared with men.

5) The approved labeling should spell out the indication for Egrifta treatment, along with indicators of effectiveness while receiving therapy, to ensure that the risk­benefit ratio is maintained for each patient. Though slice CT scans were used to measure VAT reductions in the Phase III clinical trials, these will not likely be practical in the clinical setting. Waist circumference, waist-to-hip ratio and basic psychological/body image assessments are much more feasible and should be employed by clinicians when considering patients for Egrifta and while monitoring their progress (or lack thereof), at regular time points, for as long as treatment is continued.

ATAC. 611 Broadway, #308 . New York, NY 10012.646/284-3801. admin@atac-usa.org

Page 4

6)     Approve Egrifta as a medical/reconstructive modality. We strongly urge against reviewing, approving, or labeling Egrifta as a cosmetic treatment. Though Egrifta­associated VAT reductions have not yet been established as a marker of reduced CVD risk, its effects on patients' body-image perceptions, sense of well being and quality of life is substantial. This is no different than breast reconstruction following a mastectomy-an unquestioned medical approach to minimize the negative psychological effects stemming from vital but disfiguring treatment.

In conclusion, we sincerely hope that EMDAC panelists will appreciate that the approval of Egrifta, with its favorable efficacy and safety profiles, is supported by this coalition of AIDS treatment activists that has closely followed the development of this agent, carefully scrutinized the published data and-perhaps most importantly-remains eager to see this option made available to address this long-standing unmet medical need.

Respectfully submitted,

Tim Horn Drug Development Committee AIDS Treatment Activists Coalition

cc:

Mary Parks, MD Director, Division of Metabolism and Endocrinology Products

Richard Klein Office of Special Health Concerns

Kimberly Struble, PharmD Division of Antiviral Drug Products

ATAC. 611 Broadway, #308 . New York, NY 10012.646/284-3801. admin@atac-usa.org

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