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

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

Page 5

FDA Committee Unanimously Votes to Approve Tesamorelin (Egrifta) for Lipodystrophy

http://www.hivandhepatitis.com/recent/2010/0604_2010_a.html

http://www.poz.com/articles/egrifta_fda_recommends_761_18484.shtml

FDA Committee Unanimously Recommends Egrifta for Lipodystrophy

FROM POZ.COM

May 27, 2010 FDA Committee Unanimously Recommends Egrifta for Lipodystrophy A U.S. Food and Drug Administration (FDA) advisory committee has unanimously recommended that Egrifta (tesamorelin), Montreal-based Theratechnologies' experimental product for the treatment of excess abdominal fat in HIV-positive people with lipodystrophy, be approved by the agency.  Though the FDA is not required to follow the recommendations of its advisory committees, it usually does so. Several of the 16 panelists making up the Endocrinologic and Metabolic Drugs Advisory Committee, which met May 27 at the University of Maryland University College (UMUC) Marriott Conference Centers in Adelphi, Maryland, stressed that there is a need for additional follow-up studies to monitor the long-term safety and efficacy of the drug. Egrifta is a synthetic human growth hormone-releasing factor. Phase III clinical trials of the drug indicate that it decreases visceral adipose tissue (VAT)—fat deep within the belly—by about 17 percent. According to Christian Marsolais, MD, vice president of clinical research and medical affairs at Theratechnologies, who reviewed the Phase III efficacy results at today's hearing, 57.4 percent of patients taking Egrifta experienced an 8 percent or greater reduction in VAT—the primary goals of the studies—compared with 29.3 percent of the placebo group. Unlike Serostim (recombinant human growth hormone), an earlier contender for treating excess VAT, Egrifta has long been suggested to have fewer side effects when used for at least a year, including a minimal effect on blood sugar (glucose) levels. There were, however, conflicting reports at today's hearing regarding the risk of diabetes in people receiving Egrifta in the Phase III clinical trials. Graziella Soulban, MD, director of clinical research at Theratechnologies, reported higher rates of pre-diabetes and diabetes among those receiving Egrifta, compared with placebo, during the first 26 weeks of the studies. But between weeks 26 and 52 of the studies, however, the number of people with glucose intolerance and diabetes dropped.  Ali Mohamadi, MD, a clinical reviewer from the FDA, unveiled a slightly more detailed analysis. According to the FDA safety analysis reported this morning, 49.2 percent of patients receiving Egrifta had no instances of raised blood-glucose levels. However, 17.3 percent of those receiving Egfrifta had three or more increased blood-glucose measurements during the clinical trial, compared with 7.3 percent of those receiving placebo. Mohamadi also reported that 25 percent of patients in the tesamorelin group who started off as pre-diabetic eventually went on to develop frank diabetes in the studies. Among those who began treatment without a history of diabetes and had normal glucose levels, Mohamadi confirmed, the risk of diabetes during the study remains low. Increases in insulin-like growth factor 1, or IGF-1, was another safety issue discussed at length during today's meeting. Though increases in IGF-1 are considered to be an indicator of Egrifta's activity, IGF-1 has also been suggested to promote tumor growth, which can be problematic in a population of individuals—including people living with HIV—who already face a higher risk of cancer. According to Mohamadi, a third of patients receiving Egrifta had significantly elevated IGF-1 levels. However, according to Soulban, these increases were not found to be associated with an increased risk of any type of cancer in the 52-week Phase III studies. Mohamadi reiterated that decreases in decreases in VAT associated with the use of Egrifta have not been shown to decrease the risk of cardiovascular disease—an important potential benefit of any drug that treats abdominal obesity—and several panelists reiterated that future studies should explore this goal. And though the panelists were divided on the data submitted to the FDA regarding improvements in body image and body perception in the studies, many were clearly impressed by the mid-day public testimony offered by three people living with HIV—Jeff Berry of the AIDS Treatment Activists Coalition and two Egrifta clinical trial participants—who emphasized the detrimental effects of lipodystrophy in people living with HIV. As the clock approached 4 p.m., the final vote was cast by the advisory committee members, in response to a single question put forth by the FDA: Does the risk-benefit assessment support approval of Egrifta? Sixteen voted "yes"—there were zero "no" votes and no abstentions. Several panelists stressed that follow-up data should be collected to better understand the long-term risks of glucose abnormalities and IGF-1 increases. Theratechnologies noted that it is already planning a safety monitoring program that will go into effect if the FDA agrees with the advisory committee panel and approves the drug for use in the United States. A final decision from the FDA is expected within the next two months. The agency has until July 27 to notify Theratechnologies of the drug's approval status and of any post-marketing studies that must be conducted.

Strive To Thrive While Growing Older With HIV

By Dennis McMillan Published: February 11, 2010

Nelson Vergel. Photo by Rink. Positive Force will present “Survivor Health Wisdom: Strive to Thrive While Growing Older with HIV” on Wednesday, Feb. 17, 6:30-9:30 p.m. at the San Francisco LGBT Community Center, 1800 Market and Octavia Streets. Join Nelson Vergel, author of Built to Survive, for the latest information on lipoatrophy, combating premature aging, and much more. A light dinner will be provided. To take advantage of the fact that Vergel will be in the Bay Area for a conference, Positive Force scheduled this event on the third Wednesday of the month. Twice annually, Positive Force produces a community health forum on a hot button issue. “Survivor Health Wisdom...” is a Positive Force community health forum.In this instance, they decided to do a forum on HIV and aging. The face of HIV changes with each passing day. For example, thanks to treatment advances, many people living with HIV today are living longer lives. Along with longer lives come the usual health concerns: increased risks for heart disease, non-HIV related cancers, bone loss, decreased mental function, etc. However, a plethora of recent research has clearly demonstrated that people living with HIV are suffering from accelerated aging; sometimes their minds and bodies manifest problems decades earlier than their HIV-negative counterparts. Consequentially, researchers, medical providers, treatment advocates, and HIV-positive people alike are trying to figure out how to conquer this new phase of living with HIV. Many community forums on HIV and aging involve doctors and other socio-medical professionals speaking clinically, and providing the same information, from the same point of view, time and time again. Positive Force decided to move in a different direction. They invited Vergel, a man who has lived with HIV for more than two decades and who is an internationally renowned treatment advocate, to discuss HIV and aging concerns from a peer perspective. Vergel has traveled the world talking about living and thriving with HIV; has written books on the topic; and has been featured in numerous publications for his expertise and perspective. Participants who attend the forum will benefit from Vergel’s unique perspective, presentation style, and lots of information. He will present the latest treatment information, both clinical and practical, for a range of subjects, including but not limited to lipodystrophy/ lipoatrophy, accelerated aging of both mind and body, and sexual health. Forum attendees will walk away with a better handle on how to deal with problems they may already be facing and how to prevent new problems associated with HIV and aging. Vergel is a 27-year HIV survivor, Venezuelan, retired chemical engineer, lecturer and author of Built to Survive, founder of the Body Positive Wellness Clinic in Houston, and treatment activist involved in research advocacy. Bay Times interviewed him recently. “I am the founder of pozhealth at yahoogroups.com, the largest online health discussion group, and serve as an expert at thebody.com, the HIV web site with the largest reach in HIV related health issues,” he said. “I have provided over 600 lectures since 1994 in English and Spanish. I am a member of the DHHS HIV Treatment Guidelines Panel. I have presented in many conferences about issues related to living with HIV.” What is different about what he does is his being able to lecture in layman terms by blending the latest research data with a patient perspective. He spoke of the hot topics in HIV in the next five years. “The search for a cure using stem cell and immune based therapy research will become more important as well as how to deal with long term effects of HIV medications on aging, frailty, cognitive function, bone density, frailty, body changes, and others,” said Vergel. “Combating stigma and dealing with challenges in funding will be essential to controlling the spread of this epidemic.” Vergel provides a unique angle to patients. He speaks in their language about the latest research findings on facial lipoatrophy options, cardiovascular health, sexual dysfunction, hormonal balance, exercise and nutrition, latest HIV medications for those with limited treatment options, side effect management, and many other issues that are important to patients.

An Anti-frailty Pill For Seniors? New Drug Increases Muscle Mass In Arms And Legs Of Older Adults

I bet this could compete with Theratecnologies/Serono's Tesamorelin eventually. But Merck is smart going after baby aging boomers

An Anti-frailty Pill For Seniors? New Drug Increases Muscle Mass In Arms And Legs Of Older Adults
ScienceDaily (Nov. 5, 2008) — Researchers at the University of Virginia Health System report that a daily single oral dose of an investigational drug, MK-677, increased muscle mass in the arms and legs of healthy older adults without serious side effects, suggesting that it may prove safe and effective in reducing age-related frailty.

Published in the November 4, 2008 issue of Annals of Internal Medicine, the study showed that levels of growth hormone (GH) and of insulin-like growth factor I (IGF- I) in seniors who took MK-677 increased to those found in healthy young adults. The drug restored 20 percent of muscle mass loss associated with normal aging.

"Our study opens the door to the possibility of developing treatments that avert the frailty of aging," explains Dr. Michael O. Thorner, a nationally recognized researcher of growth hormone regulation and a professor of internal medicine and neurosurgery at UVA. "The search for anti-frailty medications has become increasingly important because the average American is expected to live into his or her 80s, and most seniors want to stay strong enough to remain independent as they age."

Funded by the National Institutes of Health, the two-year, double-blind, placebo-controlled, modified-crossover study involved 65 men and women ranging in age from 60 to 81.

The study drug, MK-677, mimics the action of ghrelin, a peptide that stimulates the growth hormone secretagogue receptor (GHSR). Drug developers are focusing on GHSR because it plays an important role in the regulation of growth hormone and appetite. They think it may prove to be an excellent treatment target for metabolic disorders such as those related to body weight and body composition.

According to Dr. Thorner, the UVA research was a "proof-of-concept" study that sets the stage for a larger and longer clinical trial to determine whether MK-677 is effective in people who are frail and to assess its long term safety.


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University of Virginia Health System (2008, November 5). An Anti-frailty Pill For Seniors? New Drug Increases Muscle Mass In Arms And Legs Of Older Adults. ScienceDaily. Retrieved November 10, 2008, from http://www.sciencedaily.com /releases/2008/11/081104132902.htm