AIDS TREATMENT NEWS No. 055 - April 22, 1988
John S. James

We tape recorded part of the conversation, but we chose to quote most of the material indirectly rather than word for word, as we could not get back to Shinitzky by press time to verify the changes which would have been necessary to make our discussion clear to readers unfamiliar with AL 721. We used verbatim quotes when we could.

'AL 721' is a trademark of Ethigen Corporation, Los Angeles. The Compassionate Study In Israel

Shinitzky told us that there were two clinical trials now ongoing in Israel. The first is a compassionate trial started by Yehuda Skornick, M.D. This trial (now being conducted by other physicians because Dr. Skornick is working in the U.S.) has treated about 60 patients so far.

But this compassionate trial, Shinitzky explained, was not organized for obtaining scientific data; and therefore "the medical community will never accept such a trial for documentation".

A major problem has been the difficulty in followup. About 80 percent of the patients are from abroad. After laboratory work and diagnosis, they were given AL 721; the physicians asked them to send back data after they returned home. But most didn't comply and disappeared after they left Israel.

"We have data on only 12 of them. It's hard to make any real statement. But out of this 12 there was a clear-cut positive effect." A Scientific Trial

Shinitzky explained that in addition to this compassionate trial, Israeli researchers at the Tel Aviv Medical Center started a more scientific study with 16 patients about one year ago; the principal investigator is Dr. Yust. Unlike most U.S. studies, which try to select a more uniform groups of patients, this trial included persons with AIDS, persons with ARC, and asymptomatic seropositives within the group of 16.

Nine of the 16 were P24 antigen positive when they started; all 16 were HIV antibody positive of course. "In these nine, five showed clear-cut reduction to the basal detectable level" (apparently meaning they became antigen negative) on the Pasteur test kit used. Shinitzky noted that this result seemed compatible with the result of the only U.S. clinical trial of AL 721 completed so far, the St. Luke's/Roosevelt study in New York, in which about 60 percent of the patients showed a large reduction in reverse transcriptase (an earlier measure of viral activity, used before the P24 antigen test was available).

We asked how often the P24 antigen went negative without any treatment. Shinitzky said such cases were rare and would never happen five times out of nine.

For two of the other four patients who did not respond to AL 721, the researchers started AZT in addition to AL 721. These patients had a marked decrease in antigen; one, however, had a brain infection and died in two weeks. The other is alive and doing well. Shinitzky noted that while two cases could certainly not provide proof, it seemed that the drugs might be synergistic, working much better in combination than separately. Shinitzky also thought that the AL 721 might be reducing the side effects of the AZT.

The other two patients did not respond at all. Both of them had AIDS.

Of the five who did become antigen negative, three were asymptomatic, one had lymphadenopathy, and the other had KS, which has since disappeared. All of them feel far better than when they started.

We asked about the other seven of the 16, who had been P24 antigen negative at the start of the trial. Shinitzky said that all responded well to the treatment, but that it was hard to evaluate these cases because there was no biochemical measure to follow.

We asked if these results would be presented at the Stockholm AIDS conference in June. Shinitzky said the work had been submitted; if it is accepted the researchers will present it formally, otherwise they will finalize it for scientific publication elsewhere as soon as possible. French Study Planned

We asked Shinitzky about reports of an AL 721 study which has just begun in France.

"The French researchers, in particularly Dr. Montagnier of the Pasteur Institute, who is the key figure in AIDS research today probably in all of Europe, expressed his willingness to participate in such as study. As you know the French won't do it unless they are quite convinced.

"The head of the Israeli AIDS Association went to Dr. Montagnier's lab to learn the latest in antigen monitoring and so on. They developed good relations and together designed a protocol that later was given to other groups, including one from Marseilles. The study has just started.

"In this particular study a well defined group of people-- 100 to 200, I don't have the exact number--will be divided into equivalent groups. One will be given AZT for three months, the other will be given AL 721, and then there will be a crossover. With this design we avoid using a placebo for a control group. The results can be analyzed as a comparative study.

"Since AZT is already approved as an effective drug, if you find that our material is as effective or even further, of course it has the advantage of being nontoxic.

"And after this study is finished, both groups will be kept on AL 721. Some of them will also be given a thymus hormone, assuming that the virus has been reduced.

"In those people in whom the virus has been reduced after six months of the trial, all will be kept on AL 721, and some of them will be given a thymus hormone; the one selected was THF, thymus humoral factor, which has been analyzed and characterized at the Weizmann Institute by Dr. Trainin. So it will be a combined-treatment study, even though the beginning and the most substantial part of the study will be our compound." AL 721 Vs "Workalike" Products--Background Note

AL 721 has looked promising for almost three years, and safety has never been an issue. Nevertheless for most of this time persons with AIDS or ARC have been unable to obtain the treatment, as it was tied up in the process of seeking approval from the U.S. Food and Drug Administration (FDA) as a drug--a process originally expected to take four years, but which will probably take longer than that (even if AL 721 is in fact effective). Both Ethigen Corporation (the company which holds worldwide rights to AL 721, under license from the Weizmann Institute), and the FDA, can make a case that the delays are not their fault. Meanwhile the treatment, known to be safe and widely suspected to be significantly helpful to many people, remained unavailable.

During the last 15 months, especially the last year, self- help groups of persons with AIDS and ARC have found sources of comparable products through food-processing and pharmaceutical companies. This treatment underground has grown almost overnight until now thousands of people are using these products, commonly called "egg lecithin lipids", or just "lipids". Several informal surveys, including one which this writer conducted of over 100 users of AL 721 workalike products, have all found comparable res ults: roughly half of those who have used them are convinced they are helping, less than a quarter are convinced they are not, and the others are uncertain. (For our survey results, see SF Sentinel, August 28 1987.)

We asked Dr. Shinitzky what he thought about how these products compared to the official AL 721 as he made it in Israel. The question puts him in a difficult position, as his institution licensed exclusive worldwide rights to AL 721, and he didn't have a simple answer. He did indicate that some of the "generic" products he has seen are considerably closer than others. But the only product named in our conversation, an egg- lecithin capsule sold in health-food stores, was a "straw man" as no one considers it an AL 721 equivalent.

Shinitzky has examined the manufacturing and quality control now used for the "official" AL 721, and is happy with it.

We asked what we should look at when comparing the generic products with AL 721:

"There are two important factors that contribute to the activity of this compound. The first one is obvious: the correct ratio, 7:2:1. But even if you have separate components hypothetically and you mix them together to get the ratio 7:2:1, it won't necessarily be as potent as the original AL, because the process of production of AL, the acetone extraction, is critical, in my view.

"There is a chemical rationale. The reason we started with acetone extraction is that if you take lecithin and dissolve it in acetone, and cool it, you get separation between two components; one precipitates and the other stays in solution. We collect just one of them, this is the part that is included in the 7:2:1. Other extractions do not discriminate. I didn't realize this could be a big difference between the materials, but it turns out it's indeed so. So both the composition and the process of m anufacturing are critical."

Shinitzky warned that acetone extraction can be dangerous because this solvent is highly flammable.

(At least one of the "workalike" products--the "Nutri PE9+" from Nutricology, Inc. in San Leandro, CA--does use an acetone extraction step in its manufacturing process.) Preparing AL 721

We asked Shinitzky if it was true that AL 721 may work better if well mixed with water or orange juice, as with a blender.

Shinitzky said that there were still unanswered questions about how AL 721 is absorbed from the small intestines. But he does think that mixing the substance well in liquid (orange juice or water are often used) may make it easier to absorb. He thought that one minute in a blender would be plenty--and that one can see a change visually when the lipids are mixed well, as the mixture takes on a lighter, milkier appearance.

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