LECTURES IN FLORIDA - JUNE 2007

TOPIC: SURVIVING HIV RESISTANCE- How to avoid mistakes in using new HIV drugs

Reserve any lecture by calling 1-800- 810-3703 or email HIVSeminars@aol.com

TUESDAY, JUNE 12: MIAMI
11 am- Noon
Jackson Health System
1622 NW 12 Ave ACC West Room 125


WEDNESDAY, JUNE 13- PORT SAINT LUCIE
10:30 am- noon
5150 NW Milner Dr (off Midway Road)


WEDNESDAY, JUNE 13- FORT LAUDERDALE
6:30 pm- 8 pm
ArtServe Library
1350 East Sunrise Blvd


THURSDAY, JUNE 14- TAMPA
Baker & Company General Store & Antique Emporium
2502 N Howard

Companies Abandon AIDS Wasting Patients

On March 20, Watson Laboratories stopped the production of nandrolone decanoate (old brand name: Deca Durabolin), a low cost injectable anabolic used for HIV wasting, citing lack of raw material suppliers for the product. Patients found out when they went to their pharmacies for a prescription a week later.

Although there are other generic makers of the nandrolone internationally (easily located on the Internet), this offers little help to U.S. patients. Anabolic steroids and testosterone are designated by the Drug Enforcement Administration (DEA) as class III drugs, which are illegal to import even for personal and medical uses.

In the past 20 years, anabolic steroids have suffered from a lot of bad publicity and misconceptions due to their use in sports and bodybuilding. However, that did not stop activists in the 90’s from convincing doctors and researchers to look into these medicines to help those with HIV related wasting syndrome. Since then, over 8 studies have been performed that showed nandrolone and oxandrolone ( brand name Oxandrin, an oral anabolic) to be effective and safe for increasing lean body mass (LBM) and strength in men and women with HIV. Many physicians quickly learned how to prescribe them and monitor their use for helping their HIV positive patients to survive what used to be one of the main causes of AIDS mortality.

Watson Laboratories are the only suppliers of thirteen of the 50 AIDS Drug Assistance Programs (ADAPs) that decided to cover payment for these two anabolic agents for patients with low income. "This is the safest and most cost effective anabolic steroid in the world and now we have no manufacturer in the U.S." says Vergel.

While Watson was abandoning nandrolone, another company was making a decision that would also strain options for HIV wasting patients. Savient Pharmaceuticals informed patients in April 2007 that they stopped their 10 year old patient assistance program (PAP) that gave free Oxandrin (oxandrolone) to HIV patients with no insurance and third-party payment sources. Oxandrin, another anabolic agent used for weight gain in HIV, costs $1300 a month and most people cannot afford it. This PAP was set up by BTG Pharmaceuticals (bought out by Savient later on) in 1996 after activists pressured the company to provide the drug for free to those with no access or means. Like nandrolone, only 13 states include Oxandrin in the ADAPs , so many patients will have no way to afford this drug. Savient informed patients that Watson Pharmaceutical was to sell generic Oxandrin, and thus, there was no further need for patient assistance. Unfortunately, the generic price for Oxandrin sold by Watson is no different than the brand name product, which will still be sold by Savient. Watson will not provide free Oxandrin via a PAP either. This is the first time in AIDS history that a company stops a PAP while still selling the drug.

Oxandrin is an oral anabolic steroid used in HIV wasting and it is approved to treat unintentional weight loss due to illness. It has been shown to be midly effective in men, women and kids with HIV wasting. The advantages of this drug is that it can be taken by mouth daily (nandrolone needs to be injected in the butt once a week) and that it is approved for a weight loss related indication. However, unlike nandrolone, Oxandrin (oxandrolone) can increase liver enzymes and could be problematic for people with liver disease, taking medications heavy on the liver, HIV medications like Reyataz, and those with Hepatitis B and C.

A month supply of Oxandrin (brand name or generic) costs around $1300 for 20 mg a day. Watson’s nandrolone costed around $200 a month for 200 mg a week.

"The decisions of these two companies have a huge impact in many of my patients’ health" said Dr. Richard Loftus, a San Francisco physician with a large HIV practice. "We use nandrolone extensively in patients who have problems gaining weight and who feel fatigued, even with undetectable viral loads. Many of my patients feel better and have experienced no side effects at the doses we use in HIV”, added Dr Loftus.

Even though wasting syndrome has improved dramatically since protease inhibitors were introduced 10 years ago, some patients still need extra help to hang on to their muscle to sustain health and productivity. A study performed at Tufts University School of Medicine by Wanke et al. reported that as many as 29 percent of people with HIV in the era of HAART are still losing weight or lean body mass, despite undetectable viral loads. In the 80’s, researcher Dr Donald Kotler found that the loss of lean body mass can dramatically decrease survival in HIV-positive people

A patient and a doctor himself, Dr. Nathan Sherlock knows first hand about the importance of nandrolone for his health and that of his partner. ”My partner has had a significant problem with wasting due to AIDS and the only way he has been able to stop the dangerous weight loss is to use anabolic steroids. He is also hepatitis B positive. His doctor first prescribed Oxandrin in 1998. Within a couple of weeks he had chemical induced hepatitis with the symptoms of nausea, vomiting, loss of appetite and jaundice. His liver enzymes were all elevated. He stopped Oxandrin and the symptoms promptly resolved. His doctor then prescribed nandrolone 200mg/week and he regained weight back to his norm with no side effects. When he stops taking it the wasting returns so he has been on nandrolone for close to 9 years now”

When asked about his own experience, Dr. Sherlock adds : “I have been taking nandrolone for wasting due to AIDS for over 10 years. Every time I have stopped taking nandrolone I experience rapid weight loss that can only be reversed by resuming the use of nandrolone.”

This belief is also shared by Al Benson, a HIV treatment advocate in Los Angeles."Nandrolone is truly ‘the Lazarus drug’ …it has brought me back from the brink, restored my health and made all the difference in the quality of my life, " added Benson.

Compounding Pharmacies- A threatened last option for wasting treatments

Many doctors and patients do not know that nandrolone and oxandrolone can also be obtained legally by prescription in small quantities through compounding pharmacies at a lower cost, but those pharmacies are at risk of being shut down. The DEA has raided several in the past few months, according to one of the owners of one of the pharmacies. Senator Kennedy have tried to pass legislation to regulate these companies more heavily with the help of large pharmaceutical companies. So, no one knows how much longer this option for economical medicines will be available. Fortunately, there is a strong consumer movement to protect these outfits from closure by the government (visit savemymedicine.org)

Compounding pharmacies like Applied Pharmacy (appliedphramacyrx.com), Kronos (Kronospharmacy.com), the Compounding Shop (gotocompoundingshop.com), College Pharmacy ( collegepharmacy.com) and other companies are still economical sources of nandrolone, oxandrolone, and testosterone gels and injections. However, they do not process insurance claims and are not equipped to supply AIDS Drug Assistance Programs (ADAPs), insurance, Medicaids and Medicare Part D vendors.

What other HIV Wasting drugs are out there?

One of the FDA approved products to treat HIV wasting or appetite loss, Megace (megestrol acetate), tends to produce its weight gain due to increases in fat rather than lean body mass -- and adding fat during AIDS wasting has not been shown to improve survival. Megace, a female sex hormone based product, has also been associated with side effects such as diabetes, blood clots, impotence and the development of female sex characteristics. Another agent approved to treat HIV wasting, Serostim (recombinant human growth hormone), can cost as much as $6,000 a month, so most insurance companies do not want to pay for it and many ADAPs have limited its use due to prior bribes and scandals created by its manufacturer (Serono). Serostim requires daily injections and can cause joint aches, swelling and diabetes.FDA-approved appetite stimulants such as Marinol contain the psychoactive ingredient in marijuana (THC) that can be an issue for many people with HIV who are in recovery. Also, it's theorized that Marinol may simply owe its ability to increase weight to a side effect of the THC high -- that people get the munchies and tend to eat more.

What can you do?

A nationwide network of activists is swinging into action around this issue. Vergel says, "I feel very strongly that "quality of life" drugs need as much advocacy efforts as HIV antivirals, especially in this era when we are living longer. After all we have done as actvists to secure anti-wasting medicines, I hope we do not lose ground now and fall asleep when important medicines like nandrolone are dropped without notice.”

For more information or to find out how to help, please visit
http://savehivwastingmeds.blogspot.com/

Serono and Serostim's Corruption

This was first brough to light by Michael Mooney in 1999. It took years but Serono is now paying for this troublesome corporate decision. You can read the original article in 1999 here:

http://medibolics.com/kickback2.htm

Ex-Serono executives acquitted in USA of bribing doctors

04/05/2007
www.pharmatimes.com


A federal grand jury has acquitted four former executives of Switzerland's Serono, which has just been acquired by Merck KGaA, of charges that they illegally promoted its human growth hormone product, Serostim to treat muscle wasting in patients with AIDS.The US District Court jury in Boston set aside all charges brought in 2005 against the executives (Mary Stewart, John Bruens, Melissa Vaughan and Marc Sirockman) at Serono, which included conspiracy and giving doctors expenses-paid trips to Cannes, France for a medical conference in 1999 where they agreed to write up to 30 prescriptions for Serostim (somatropin), typically costing $21,000 for a 12-week treatment.At about the same time the US Food and Drug Administration approved the drug, protease inhibitors came on the market, making patients less prone to AIDS wasting. Demand for Serostim began to fall and at a meeting in Boston in March 1999, Mr Bruens and Ms Stewart told Mr Vaughn, Mr Sirockman and several other regional sales directors that they needed to "dig their way out" of a financial crisis, according to the indictment.Sales reps were required to identify the highest prescribing physicians in their region and then target them with free trips to boost prescriptions to $6 million in 6 days, prosecutors had claimed."We believed this is a case that should not have been brought and the speed with which the jury returned its verdict (just three hours) confirmed our beliefs," said Adam Hoffinger, an attorney for Ms Vaughn. He added that the trip was not offered in exchange for writing prescriptions for Serostim, noting that the defendants "had no intent to bribe any doctors, and they did not bribe any doctors. It was a legitimate medical conference."Serono agreed a deal with the US Justice Department in October 2005 to plead guilty and pay $704 million to settle charges that it knowingly encouraged the submission of fraudulent claims for Serostim reimbursement under government health programmes.ReutersIt also agreed in 2005 to plead guilty to two criminal charges and to pay a $137 million fine resolving an investigation into how the company marketed the drug called Serostim, which was approved by the U.S. Food and Drug Administration in 1996.The drug was marketed in the United States by Serono Inc. of Rockland, Massachusetts.Also in 2005, Serono agreed to pay $567 million to settle civil charges that it knowingly caused the submission of false claims for Serostim that were not eligible for reimbursement under government health programs.>From 2005 Boston Globe:Some HIV/AIDS advocates have said the "bad blood" with Serono will not affect their position on new uses for Serostim, the Globe reports. However, "it's clear this vocal and influential constituency, which often weighs in with regulators on AIDS drugs, now doesn't trust Serono and will be skeptical of any new promises or clinical claims from the company," according to the Globe


IF YOU HAVE PAID FOR ANY PART OF SEROSTIM'S PRESCRIPTION IN THE PAST, READ THIS:

Mr. Vergel:

I am an attorney involved in the settlement of litigation against Serono. There's about $2 million available to reimburse anyone who paid anything out of pocket for Serostim. Despite our best efforts to date to spread the word about the settlement and the availability of the money, very few have filed proofs of claim and most of the money is at risk of going unclaimed.

If you think you can help publicize this, please contact me. Your services would not be compensated, so you'd have to be interested in this as a pro bono project.

Richard W. Cohen
Lowey Dannenberg Bemporad Selinger & Cohen, P.C.
White Plains Plaza
One North Broadway, 5th Floor
White Plains, NY 10601
914-997-0500 (main line)
914-733-7239 (direct line)
rcohen@lowey.com

AIDS activists upset by dropped wasting drug

Copyright © 2006 Bay Area Reporter, a division of Benro Enterprises, Inc.
AIDS activists upset by dropped wasting drug
by Heather Cassellh.cassell@ebar.com


AIDS activists are mobilizing after Watson Pharmaceuticals last month dropped a common off-label drug used to assist patients with combating wasting and picked up a generic brand of an approved AIDS-related wasting medication that they maintain is not as effective.

"Taking this drug away from people with wasting syndrome is like taking insulin away from diabetics," said Jason Riggs, deputy director of the Stop AIDS Project. "Thousands of people with HIV depend on this drug to reverse wasting syndrome, a life-threatening illness."
Patricia Eisenhaur, director of investor relations for Watson Pharmaceuticals, confirmed that Deca-Durabolin, also known as nandrolone decanoate, an anabolic steroid prescribed by physicians to combat AIDS wasting, was discontinued on March 20.

According to Eisenhaur, the active ingredient to manufacture the drug was no longer available from the Food and Drug Administration-approved supplier. Eisenhaur was unable to provide the name of the supplier, which was the only approved manufacturer of the active ingredient. She told the Bay Area Reporter that the supplier did not provide Watson with a particular reason for not being able to provide the ingredient for the medication.
"We depleted all of our existing inventory and we've done everything we can to keep the product on the market," said Eisenhaur. "But without access to the active ingredient we obviously can no longer manufacture and distribute this product."
Eisenhaur told the B.A.R. that Watson notified its customers – mainly hospitals, wholesalers, and those who purchase products directly from the company – about the discontinuation of the medication through its normal communications process. Watson did not issue a news release regarding its decision and the company does not plan on making any further public announcements, according to Eisenhaur.
AIDS activists upset
On April 4, Sanford Gross, an associate professor at Illinois College of Optometry, posted on the Yahoo Group PozHealth his discovery that Deca-Durabolin was discontinued by Watson.
AIDS physicians and activists don't believe that the raw ingredient used to make the medication isn't available. During an AIDS Treatment Activist Coalition phone conference on April 13 to discuss actions to mobilize to have the medication returned to the market, there was speculation about Watson's decision. Their suspicions grew through this week as they learned that Savient Pharmaceuticals canceled its patient assistance program for Oxandrin, the second most prescribed drug to combat wasting.
Savient made that decision soon after Watson was approved to manufacture a generic brand of Oxandrin in December 2006.
"The company has always been pleased to provide the patient assistant programs over the past several years," said Anne Marie Fields, investor relations of Savient. "That's pretty common to cancel patient assistant program for a drug when it goes generic. It just makes sense. The increase of the introduction of the generic and reduction of the price makes the product more accessible for the patients that need them."
"We are one of the broadest distributors of generic products of the United States," said Watson's Eisenhaur. "So having an opportunity to offer new products to our customers is important to us."
Eisenhaur told the B.A.R. that the decisions for both drugs were unrelated. According to Eisenhaur, Deca-Durabolin "in terms of Watson's overall revenues, it is a small product."
AIDS doctors and activists aren't satisfied with responses from Watson and Savient.
"I think it's important for citizens to realize that our health care system for the last 30 years has slowly been hijacked by corporations," said Dr. Richard Loftus of California Pacific Medical Center, Davis Campus.
But not all activists were quick to blame Watson.
"I'm reluctant to put this squarely on the shoulders of Watson Pharmaceuticals," wrote Tim Horn, senior writer and editor for http://www.AIDSmeds.com, in a e-mail. "The fact is, we – treatment activists – dropped the ball. We should have been pushing for the approval of nandrolone as a bona fide treatment for HIV/AIDS-related wasting 10 years ago ... I just don't see how we're to be at all effective in terms of pushing a company to continue manufacturing a drug for an indication it doesn't even have."
Which can possibly explain some of AIDS physicians' complaints that Watson didn't notify them. Deca-Durabolin isn't approved by the FDA for doctors to prescribe to their HIV-positive and AIDS patients to treat AIDS-related wasting. It was approved for treating anemia, according to Horn.
According to the FDA's Web site, Deca-Durabolin is an anabolic steroid that was first approved by the FDA in 1962. The Web site also stated that there is no alternative therapy.
This wasn't news to physicians treating AIDS patients and activists who are troubled by the changes. The medication was highly successful with low side effects, was cost effective, and was included in the AIDS Drug Assistance Program.
According to Loftus and AIDS activists, there aren't very many viable options available on the market to assist patients with combating AIDS-related wasting. What is also troublesome to them is that the options aren't as effective treating the condition.
AIDS physicians and activists repeatedly cited the fact that Deca-Durobolin was studied thoroughly, including for AIDS-related wasting. The studies showed that the medication has many benefits, according to Loftus and those that participated in the conference call. One of the benefits is that it has few side effects compared to alternative steroids, such as Oxandrin, Loftus noted.
He said that the problem with Oxandrin is that it has common side effects, but more important, it damages the liver. Deca-Durabolin did not. Oxandrin, the second most prescribed anabolic steroid, is also more expensive.
According to Nelson Vergel, founder of the Program for Wellness Restoration in Houston, Texas, who coordinated the conference call, AIDS-related wasting isn't the "number two HIV killer anymore in the United States, it is now number eight." He believes this is due to life-expanding medications, such as protease inhibitors, commonly referred to as "cocktails."
That doesn't make a difference to Loftus, who prescribes the medication, or patients who depend on the medication to help them continue living healthy lives.
"We have a real urgent need to treat weight loss in these patients for the sake of survival," said Loftus.
This isn't the first time Deca-Durabolin was removed from the market. Organon International, a New Jersey pharmaceutical company, dropped the drug from distribution in 2002 with no plans to return it to the market. AIDS activists mobilized at that time as well. Eventually, Watson picked up the medication. ATAC is hoping this will happen again.
"This is a decision that effects many people's health that was made by a corporation that did not even have the courteousness to consult patient groups about this decision," said Loftus. "This goes back to an old adage that we used to say in ACT UP 15 years ago, 'Their right to own the drug is more important than our right to have access to it to save our lives.'"
Loftus said about 90 percent of his patients with full-blown AIDS and 40 percent of his HIV-positive patients are on Deca-Durabolin. He sees about 300 AIDS and 1,700 HIV-positive patients. He found out about Deca-Durabolin's discontinuation from Gross's posting on PozHealth, but he never received a notification from Watson. According to Loftus, Walgreens pharmacy confirmed Watson's decision on April 17.
For more information on the campaign to put Deca-Durabolin, back on the market, visit http://watsonboycott.blogspot.com/.
04/19/2007

My Upcoming Lecture in Wilmington , DE

Surviving HIV Resistance in the new era of HAART

Date: 04/25/2007
Time: 12-2 p.m.
Place: Doubletree Hotel
Address: 700 King St.
City: Wilmington
State: Delaware
Zip: 19801
Contact Person: Lori Campbell
Organization/Company: AIDS Delaware
Contact Email: campbell@aidsdelaware.org
Contact Phone: 302-652-6776
Contact Fax:
Event Description:
A lecture for patients and clinicians. Topics include how to avoid serious mistakes in choosing the right combinations, data on new medications and how to predict the best response in the treatment of patients with multi-drug resistance. Nelson Vergel,BsChE, founder of salvagetherapies.org, powerusa.org and the Body Positive Wellness Clinic in Houston, will be the featured speaker.


http://www.delawarehiv.org/calendar_view_details.cfm?new_event_date=04/25/2007&id=285&type=state

STOP CONGRESS FROM DENYING US COMPOUNDED MEDICINES

Compounded medications have greatly improved the quality of the lives of many people living with HIV. Several of these medications (hormone therapies, wasting therapies, quality of life therapies) are not cover by most insurance or ADAP/Medicare/Medicaid formularies, so patients rely on access through compounding pharmacies. Now, access to these medications is facing a huge threat.

A small but powerful group of senators is on the verge of introducing legislation that would severely restrict and possibly deny access to critical medications that many patients rely on, such as women prescribed bioidentical hormones, hospice care patients and children.

Even if you don't currently rely on compounded medicines yourself, you may need them someday - and you know someone who needs them now. Please join me in contacting Congress to stop this legislation and protect patient access to compounded drugs! Visit www.savemymedicine.org to take action.


This is a copy of the letter that savemymedicine.org sends to your congress people after you input your name and address.

Apr 9, 2007

Senator John Cornyn
United States Senate
517 Hart Senate Office Building
Washington, DC 20510-0001

Dear Senator Cornyn,

I know that you are committed to protecting patients and, as a result,
I hope that you share my concerns about the draft Safe Drug
Compounding Act of 2007 that may soon be introduced by Senators Edward Kennedy, Richard Burr and Pat Roberts.

I rely on compounded medications. Without access to them, I will
suffer.

The Safe Drug Compounding Act would restrict and possibly even deny my access to vital compounded medications, medications that my doctor
has determined I need.

As your constituent, I strongly urge you to oppose this legislation
and look forward to hearing your response.

Sincerely,

Mr. Nelson Vergel

*************************************************************************

WATSON PHARMACEUTICALS ABANDONS AIDS WASTING DRUG

FOR MORE INFORMATION ABOUT THIS GO TO http://watsonboycott.blogspot.com/

April 4, 2007



Allen Chao, PhD

Chairman and CEO

Watson Pharmaceuticals

Corporate Headquarters
311 Bonnie Circle
Corona, California 92880

Dear Dr Chao :





I am writing to ask you to reverse your decision of stopping the manufacture of nandrolone decanoate. I am a national treatment advocate and person living with AIDS who has used your product in the past to reverse wasting syndrome and sustain my lean body mass and quality of life. Several HIV studies have shown that nandrolone prevents and reverses the loss of lean body mass (LBM) that has been linked to increased risk of death in HIV while increasing strength and functional capacity. Your decision to abandon this compound affects me, my work, and thousands of people who needed it to keep living a productive life.



At an average cost of $200 a month for dose of 200 mg a week, nandrolone is a lot more cost effective and more tolerable wasting treatment than recombinant human growth hormone (Serostim) ( cost: $6000 a month). You are the sole supplier of several federal-funded AIDS Drug Assistance and Medicaid programs that have recognized its value and have included nandrolone in their formularies to treat thousands of low income HIV-positive patients nationwide.



I have been told by people in your company that you do not have a source of raw materials anymore. It seems that several raw material suppliers are still available. I certainly hope that your decision has not been originated by the DEA and media frenzy over anabolic steroid use in sports. This negative media exposure completely ignores the important medical uses of this medication. For whatever reason, it is irresponsible for Watson to stop supplying this product without a successor that can guarantee that patients in need get access to this important drug.



Thus, unless you decide to reverse your unfortunate decision of abandoning nandrolone decanoate, our organization and many key stakeholders will start a campaign to boycott Androderm and Watson's other products via press releases, emails and direct mailings to physicians. I certainly hope we do not have to go to these extreme measures and that you show compassion towards people living with HIV.



Please have someone from your medical and legal department call me directly at 713-539-1978 to discuss this matter before the patient and physician communities are activated.



Sincerely,









Nelson R. Vergel



Director







cc:



Mr Jeff Murray- Food and Drug Administration

Ms Karen Tandy- Drug Enforcement Administration
Mr Steve Baragona- HIV Medicine Association (HIVMA)

Mr Rob Banaszak- The American Academy of HIV Medicine (AAHIVM)

Ms. Cathy Olufs- President- The AIDS Treatment Activist Coalition (ATAC)

Free HIV lecture in Houston on April 19, 2007

Title: Latest Update on HIV Research

Seminar date : April 19, Thursday

Time: 6:00 pm til 8:30 pm

Free dinner and door prizes

Speakers: Shannon Schrader MD
Nelson Vergel (powerusa.org)


LOCATION:
United Way of the Texas Gulf Coast
50 Waugh Drive
Houston, Texas 77007

For more information email : nelsonvergel@yahoo.com

Letter to the FDA about ways to improve Expanded Access Programs of Investigational Drugs in HIV

From a meeting held by the Forum of Collaborative HIV Research. The list of participants is at the end of the letter. I certainly hope that the FDA encourages industry to implement these recommendations. Great ideas have died due to lack of action.

March 11, 2007





The Forum for Collaborative HIV Research, an independent public/private partnership that includes government agencies, pharmaceutical and diagnostic industries, HIV researchers and clinicians, payers, foundations, and the HIV patient advocacy community organized a roundtable discussion on February 16, 2007 to discuss how current and future HIV antiretroviral expanded access programs (EAPs) might be improved so that they best meet the needs of patients, clinicians, industry sponsors, and regulatory agencies. This roundtable meeting was the first opportunity for all of the relevant parties to talk about improving expanded access programs for antiretroviral agents. As such, it was a valuable opportunity not only to listen to the concerns and perspectives of the various constituencies, but also to realize how much their interests align in support of providing access to therapies for patients with few treatment options.



We submit the following comments and recommendations to the FDA Docket No. 2006N-0062 and RIN 0910-AF14.



Introductory comments:



Expanded access programs were developed in order to make promising treatments available to patients who need them as early in the drug evaluation process as possible. In particular, the goal is to make such drugs available to patients who have exhausted all currently approved therapies. Early in the HIV epidemic, HIV activist organizations challenged the existing drug approval system as too cautious, particularly in the face of a deadly epidemic that was claiming thousands of lives for lack of effective therapies. Their efforts shifted the balance from the strictly protective model with an emphasis on preventing harm to patients toward increasing access to potentially effective therapies for patients who are in need.



The HIV field likely has the most experience with expanded access programs compared to other diseases. Twenty-one drugs have previously been made available through expanded access programs in the United States and an additional three drugs are currently available through expanded access programs for people living with HIV.



At present, the approach to EAPs is to have each company’s program (independent of other companies) precede the release of new antiretrovirals prior to FDA approval. Major concerns to this approach within the HIV scientific, medical and activist communities include the increased risk of drug resistance when adding a single new agent to a failing regimen (or “virtual monotherapy”), potentially leading to a transient response but reduced long-term durability; and the risks associated with using untested combinations of drugs before the potential for drug interactions has been systematically studied.



Key issues in HIV-therapy related EAPs:



The size of the patient population that currently needs access to investigational antiretroviral drugs is difficult to estimate. We recognize that such patients do still exist and that the size of the population is probably decreasing, but convincing data to indicate the number of patients in need of early access is lacking. In addition to the criteria of failing a third regimen, a key factor in the equation is the urgency of the patient’s need for new therapy.
Tension exists between the clinical and research aspects of EAPs. While the primary rationale for EAPs is to provide early access to drugs for patients in need, there are secondary competing interests in terms of the requirements to collect useful safety data on emerging compounds that might identify unknown safety issues and ultimately help guide treatment strategies. However, current data collection practices rarely yield useful information.
EAPs are associated with a heavy administrative burden that limits the ability of some sites to participate and these programs are unfunded or underfunded. This burden appears to be particularly acute in the academic research setting, where intensive IRB approval and oversight combined with the data collection requirements of the protocols has forced some centers to forego participation in EAPs until they can find a way to pay for them. As sites refuse to participate, this limits patient access to the EAP.
EAPs need to be conceived of within the context of clinical strategies overall. As the HIV epidemic and antiretroviral treatment strategies have evolved, it is no longer advisable to give patients new drugs without ensuring other active agents in the regimen. Otherwise patients would effectively be receiving virtual monotherapy and risk the development of drug resistance and subsequent regimen failure.
Geographic limitations continue to impede access for patients in small cities and in rural areas. Ideally, the system should be able to provide access to experimental drugs for all patients who need them and qualify for EAPs regardless of where they live.
Information about the EAPs can be quite difficult to find. Some companies do not list sites participating in their EAP on their own websites or on database websites like clinicaltrials.gov, making it very difficult for patients and their physicians to know where they might access experimental agents outside of clinical trials. Similarly, companies may not adequately advertise the existence of their EAPs. Industry is particularly concerned about the perceived appearance of pre-approval marketing.




Specific Recommendations:



· Explore the potential for standardization of EAP data collection requirements and safety reporting. This could reduce the redundancy in the current system and simplify participation in multiple simultaneous EAPs.

· Consider further collaboration between regulatory agencies and the pharmaceutical companies in the design of EAPs to include the simultaneous use of multiple investigational agents and to identify creative study designs that will limit the use of virtual monotherapy and address the evolving therapeutic needs of patients.

· Explore standardizing EAP protocols so that some of the administrative work (example being submission to IRBs) can be lessened.

· Explore the potential collaboration between the FDA and other regulatory bodies to standardize and minimize the burden, as much as possible, for the very complex and variable regulatory requirements for EAPs.

· Explore how the pharmaceutical companies can standardize their EAPs in terms of development of case report forms and adverse events reporting.

· Provide guidance to contract research organizations (CROs) on data collection requirements such that the administrative burden for an EAP is reduced compared to a standard clinical trial.

· Apply and take advantage of technological modernization in adverse event reporting. For example, a centralized electronic database could provide access to basic tabulation and analysis of the voluminous serious adverse event reports that in their present form are virtually useless to the individual site investigators and site IRBs.

· Consider a two tiered expanded access approach: one would be an actual research protocol designed to address specific questions leading to approval, and which would be appropriately reimbursed like any other clinical trial. Such a protocol could address the types of issues normally studied in Phase 4 studies. These could be designed to target underrepresented patient populations. The second parallel approach could be a simplified protocol, similar to the current EAP protocols. However, both tiers likely would need reimbursement to participating institutions due to non-recovered costs of participation in the EAP.







A full report from this roundtable discussion will be available on the Forum for Collaborative HIV Research’s website at http://hivforum.org/projects/Expanded%20Access.htm





Forum for Collaborative HIV Research

Rethinking the Approach to Expanded Access Programs

February 16, 2007

Washington, D.C.





Valerianna Amorosa, M.D.

University of Pennsylvania


Christine Balt, M.S., R.N., APRN-BC, AACRN
Indiana University Division of Infectious Diseases

Association of Nurses in AIDS Care



Debra Birnkrant, M.D.

FDA


Rob Camp

ACTG NCAB



Ben Cheng, M.Sc.

Forum for Collaborative HIV Research


Joel Gallant, M.D., M.P.H.

Johns Hopkins University School of Medicine



Roy Gulick, M.D., M.P.H.

Cornell University


Michael Horberg, M.D., M.A.S., F.A.C.P.

Kaiser Permanente



Ernest Igwacho

Forum for Collaborative HIV Research


Daniel Kuritzkes, M.D.

Harvard Medical School



Katherine Laessig, M.D.

FDA


Randi Leavitt, M.D., Ph.D.

Merck & Co., Inc.



Meagan Lyon, M.P.H

Forum for Collaborative HIV Research


Bill Mannion, R.N., B.S.N.

Pfizer, Inc.



Karen Manson

Tibotec BVBA


Kendall Marcus, M.D.

FDA



Scott McCallister, M.D.

Panacos Pharmaceuticals


Marita McDonough, R.N., M.P.A.

Boehringer Ingelheim Pharmaceuticals, Inc.



Luis Mendao

European Aids Treatment Group


Veronica Miller, Ph.D.

Forum for Collaborative HIV Research



Nathalie Morgensztejn

EMEA representative for the HIV Forum


Jeff Murray, M.D., M.P.H.

FDA



Linda Onaga
Forum for Collaborative HIV Research


Frederick Schmid, D.V.M., M.B.A.
Panacos Pharmaceuticals


Kimberly Struble, Pharm.D.
FDA
Pablo Tebas, M.D.
University of Pennsylvania



Randall Tressler, M.D.
Pfizer, Inc.



Nelson Vergel, B.Ch.E., M.B.A

Salvagetherapies.org



Douglas Ward, M.D.

Dupont Circle Physicians Group


Eric Zechman

Medical Writer

Do not do as I did

Please read the article written by Enid Vazquez in the latest Positively Aware, one of the main free HIV magazines distributed around the U.S.


My comments are in the last part in the section called "Don't do as I did"

I want to make sure that people who are applying for TMC 125 expanded access are very careful when assuming that this medication will be represent an "active" agent. No genotype test for EAP drugs is available, so we are in danger of assuming that a new drug is an active drug (this assumption may not be true when starting drugs in existing classes). An active drug is one that is shown in your resistance test (genotype or phenotype) to have a good chance to work in controlling your virus. Another danger with TMC 125 is that it is a NNRTI and we know that prior NNRTI resistance can be archived and not show up in genotype tests. Many patients like myself with extensive NNRTI resistance in the past show activity to that class in our genotype test. If the doctor does not carefully review prior medication history and asks the right questions to the patient, both the doctor and patient will assume that there is no archived prior resistance. So be very careful!

If you are to start a new combo with MK 518 integrase inhibitor, a drug that is showing more promise than most for patients with multidrug resistance, make sure that you start it with Fuzeon (if you are Fuzeon naive) and/or Maraviroc (if you have a R5 tropic virus) unless you can be 100 % certain that TMC 125 will work on your virus. With all the hype surrounding TMC 114, I made the terrible assumption about the activity of TMC 114 (Darunavir, Prezista) when I got that drug via EAP to start it with MK 518 as part of Merck's phase III study. Read more in the link below.


Around 30 % of people who have extensive Kaletra and protease resistance may have pre-existing resistance to Aptivus (Tipranavir) and/or Prezista (Darunavir). No one is talking about this and there are a few conference posters on the subject but not discussed by anyone. Do not fall prey of the hype that is built around new medications, unless they are in a new class that you have never taken before and that show great response. This is the best chance for many of us to attain undetectable virus and hopefully keep it that way for a long time, if you do it right the first time.

http://www.tpan.com/publications/pa/07_02/tales_of_salvage.shtml