Reduced Limb Muscle, More Belly Fat Linked to Higher Mortality

http://www.hivandhepatitis.com/2011_conference/croi2011/docs/0322_2010b.html

A good reason to do resistance exercise, use nandrolone if needed, and manage lipodystrophy.

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

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

Page 5

Survey: Most patients with HIV lipodystrophy are willing to inject Egrifta once a day to reduce their visceral fat

 LIPODYSTROPHY TREATMENT- PATIENT ACCEPTANCE

DownloadCreate Chart1. Has your belly fat increased after starting HIV medications?
	answered question		85
	skipped question		2
		Response Percent	Response Count
Yes		92.9%	79
No		7.1%	6

DownloadCreate Chart2. Would you be willing to inject a drug daily under your skin in your belly to decrease your belly fat by 13% in 26 weeks?
	answered question		87
	skipped question		0
		Response Percent	Response Count
Yes		83.9%	73
No		16.1%	14

Impact of Lipodystrophy on Quality of Life of People Living With HIV- Survey Results

1. How old are you?
	answered question		1,325
	skipped question		6
		Response Percent	Response Count
Under 15 years old		0.3%	4
15-20		0.2%	2
20-25		0.5%	7
25-30		1.7%	23
30-35		4.8%	63
35-40		7.8%	104
40-45		23.1%	306
45-50		22.6%	299
50-55		20.8%	275
55-60		11.4%	151
Over 60		6.9%	91

DownloadCreate Chart2. What is your ethinicity?
	answered question		1,325
	skipped question		6
		Response Percent	Response Count
White		78.4%	1,039
Black		7.7%	102
Latino		9.1%	121
Asian		1.7%	22
American Indian		0.8%	10
Other		2.3%	31

DownloadCreate Chart3. What is your gender?
	answered question		1,325
	skipped question		6
		Response Percent	Response Count
Female		12.4%	164
Male		87.2%	1,155
Transgender		0.5%	6

DownloadCreate Chart4. How long have you known that you are HIV positive?
	answered question		1,325
	skipped question		6
		Response Percent	Response Count
Under 5 years		10.1%	134
5- 10 years		14.1%	187
10-15 years		20.8%	276
15-20 years		27.7%	367
over 20 years		27.2%	361

DownloadCreate Chart5. Are you currently taking HIV medications?
	answered question		1,325
	skipped question		6
		Response Percent	Response Count
Yes		94.9%	1,258
No		5.1%	67

DownloadCreate Chart6. If you are taking or have taken medications for HIV, how long have you taken them (total years)?
	answered question		1,288
	skipped question		43
		Response Percent	Response Count
Under 5 years		15.0%	193
5-10 years		21.1%	272
10-15 years		35.3%	455
15-20 years		28.6%	368

DownloadCreate Chart7. Have you taken any of these medications in the past?
	answered question		1,170
	skipped question		161
		Response Percent	Response Count
Zerit (D4T)		83.6%	978
AZT		78.7%	921
Crixivan		50.3%	589
High dose Norvir		37.1%	434
Hydroxyurea		11.2%	131
DDI (videx)		55.0%	644
DDC (Hivid)		29.4%	344

DownloadCreate Chart8. Have you had body shape changes after starting HIV medications in the past?
	answered question		1,331
	skipped question		0
		Response Percent	Response Count
Yes		88.7%	1,180
No		11.3%	151

DownloadCreate Chart9. What kind of body changes are you experiencing or have you experienced?
	answered question		1,296
	skipped question		35
		Response Percent	Response Count
Involuntary weight loss/wasting		45.8%	594
Abdominal (Belly) Fat Gain		61.9%	802
Facial Wasting		79.9%	1,035
Butt Wasting		70.3%	911
Veiny Legs or Arms		68.5%	888
Increased Breast Size		21.1%	274
Buffalo Hump (Behind The Neck)		20.9%	271
Increased Neck Size		16.4%	213
Parotid Gland Enlargement (sides of face)		15.7%	203
Other		6.4%	83
Show repliesIf other, please specify			106

DownloadCreate Chart10. Have you experienced depression or anxiety due to the body changes?
	answered question		1,331
	skipped question		0
		Response Percent	Response Count
Yes		88.4%	1,177
No		11.6%	154

DownloadCreate Chart11. Have you ever thought of killing yourself due to your body changes?
	answered question		1,331
	skipped question		0
		Response Percent	Response Count
Yes		26.3%	350
No		73.7%	981

DownloadCreate Chart12. Have you ever thought about not taking your HIV medications or have you ever stopped taking them because of fear of worsening your body changes?
	answered question		1,331
	skipped question		0
		Response Percent	Response Count
Yes		42.4%	564
No		57.6%	767

DownloadCreate Chart13. Have the body changes cause you to: (check all that apply)
	answered question		1,256
	skipped question		75
		Response Percent	Response Count
Stop socializing and going out to meet people		67.4%	847
Stop dating		51.8%	651
Decrease sexual activity		73.9%	928
Increase sexual activity		3.9%	49
Worry too much about people finding out you are HIV+		61.2%	769
Be rejected by potential sexual partners		56.0%	703
Affect your job performance		27.4%	344
Stop looking at yourself in the mirror		58.0%	729
Change your clothing style		56.0%	703
Abuse drugs or alcohol to feel better		18.2%	228
Deplete your finances in search of a solution		29.2%	367
Other		6.7%	84
Show repliesPlease Specify			112

DownloadCreate Chart14. What have you done to try to reverse your body changes? (check all that apply)
	answered question		1,242
	skipped question		89
		Response Percent	Response Count
Exercised more		72.6%	902
Watch what I eat		72.4%	899
Got my face injected with a filler or cosmetic product		40.7%	505
Got my parotid glands treated with radiation		1.4%	18
Took supplements that I heard may help my body fat/muscle		43.0%	534
Used testosterone		45.0%	559
Used human growth hormone		17.1%	212
Used nandrolone (Deca durabolin)		16.1%	200
Used Oxandrin		13.8%	171
Got liposuction		7.2%	90
Got butt implants		1.7%	21
Use padded underwear		13.3%	165
Other		6.6%	82
Show repliesIf other, please specify			118

DownloadCreate Chart15. Have your insurance, ADAP/Ryan White clinic, HMO, health care system (for countries outside the US) and/or supplier patient assistance program paid for ANY of the solution(s) mentioned in the answer(s) in the previous question? (Check all that apply)
	answered question		1,124
	skipped question		207
		Response Percent	Response Count
No one has. I had to pay with my own money		63.2%	710
Yes, my insurance company has		17.7%	199
Yes, my HMO has		4.7%	53
Yes, my ADAP/Ryan White program has		6.9%	78
Yes, my country's health system has		7.9%	89
Yes, a supplier's patient assistance program has		11.1%	125
Show repliesPlease specify what was paid for			279

DownloadCreate Chart16. Have you had facial wasting (lipoatrophy)?
	answered question		1,330
	skipped question		1
		Response Percent	Response Count
Yes		80.3%	1,068
No		19.7%	262

DownloadCreate Chart17. What option have you used to improve your facial lipoatrophy? (check all that apply)
	answered question		1,144
	skipped question		187
		Response Percent	Response Count
I have done nothing		41.3%	472
I have used BioAlcamid		7.1%	81
I have used silicone		6.8%	78
I have used Sculptra (New Fill or polylactic acid)		29.6%	339
I have used Radiesse		5.2%	60
I have used PMMA in Rio, Tijuana or other		4.4%	50
I have switched off from Zerit to Viread, Ziagen, Epzicom or Truvada		31.0%	355
I have switched off from AZT to Viread, Ziagen, Epzicom, or Truvada		12.3%	141
I have taken Uridine (Nucleomaxx)		1.1%	13
Other		8.4%	96
Show repliesplease specify			157

Show this Page Only

PAGE: PAGE 2

DownloadCreate Chart18. Do you have or have you had high cholesterol/triglycerides?
	answered question		1,297
	skipped question		34
		Response Percent	Response Count
Yes		65.8%	853
No		28.0%	363
I do not know		6.2%	81

DownloadCreate Chart19. Have you had or do you have higher than normal blood glucose (sugar)?
	answered question		1,297
	skipped question		34
		Response Percent	Response Count
Yes		27.4%	356
No		58.7%	761
I do not know		13.9%	180

DownloadCreate Chart20. Have you heard from your doctor or other sources that belly fat, high LDL (bad) cholesterol, high triglycerides or high blood sugar may affect your health and mortality?
	answered question		1,297
	skipped question		34
		Response Percent	Response Count
Yes		75.5%	979
No		19.8%	257
I do not remember		4.7%	61

DownloadCreate Chart21. Do you think some HIV medications can increase belly fat?
	answered question		1,296
	skipped question		35
		Response Percent	Response Count
Yes		81.8%	1,060
No		0.6%	8
Not sure		15.6%	202
I think HIV causes it, not the medications		2.0%	26

DownloadCreate Chart22. Do you think some HIV medications can increase fat loss under the skin (facial wasting, veiny legs/arms, fat loss in the butt)?
	answered question		1,296
	skipped question		35
		Response Percent	Response Count
Yes		88.8%	1,151
No		0.8%	11
Not sure		6.9%	89
I think HIV causes it, not the medications		3.5%	45

Download23. What do you want me to tell or ask lipodystrophy researchers about what the research needs are for that problem?
	answered question	690
	skipped question	641
		Response Count
Show replies		690