Health Spectator

Reuters is reporting that a Senate panel has voted today to approve a path for getting generic biologic drugs to market faster. Biologics—unlike synthetics—are drugs that are derived from living things and are consequently often quite difficult and expensive to make. Because their manufacture is so sensitive to the slightest changes in starting substances or altered processes, there has to date been no mechanism in the U.S. for generic biologics to be produced, unlike the case with the more common “small molecule” drugs such as aspirin.

Perhaps the most commonly known examples of biologics would be vaccines. Less well known would be epoeitin alpha, a member of the class of erythropoietic proteins, marketed as Procrit (sold by Johnson and Johnson) and as Epogen, sold by Amgen.

The entire subject is fraught with controversy, with manufacturers who hold patents for biologics arguing that they cannot be duplicated in the same way that small-molecule drugs subject to traditional chemical manufacturing techniques are.

The area is also one with strong political overtones, as evidenced by the current Senate bill’s authors: Senators Edward Kennedy (D, Mass.), Hilary Clinton (D., N.Y.), Mike Enzi (R, Wyo.), and Orrin Hatch (R, Utah). No doubt democrats see a political windfall in breaking into the previously sacrosanct area of biologics.

The current Senate version of the bill would require generics manufacturers to run at least one clinical trial to demonstrate that their version of the drug was medically no different from the name-brand equivalent. However, a provision that may alarm the name-brand manufacturers allows the FDA to waive the clinical testing by relying on animal testing or other data.

What’s more, the FDA would have the power to declare a copycat drug as interchangeable, meaning that it could be substituted for its name-brand equivalent.

In order to qualify to become a generic, a drug must have been manufactured for at least 12 years and its patent must have expired. Most of the current controversy centers on the 12-year manufacturing requirement. Traditional drug-industry supporters see the time as too short, while generics manufacturers and consumer support groups argue it is too long.

We felt glued to our seats. My wife and I were sitting in a small cafe in southern New Hampshire—the only diners in the place—and on the TV in the corner was Neil Cavuto on Fox TV conducting an interview (a debate, really) about the new over-the-counter weight-loss pill just approved by the Food and Drug Administration: Alli.

A fitness expert was trying valiantly to argue, in effect, that Alli was the work of the devil, pointing out its negative side effects and advocating a saner approach to weight loss that might involve, say, proper diet and exercise. But she was outgunned—outgunned by Cavuto himself and his MD interviewee, Fox’s own health commentator, Dr. Manny.

While watching this one-sided boxing match in which the underdog was throwing all the right punches and still couldn’t seem to score at round’s end, we had an epiphany: What’s most noticeable about all the publicity Alli is getting is that the medical community seems to be bending over backwards to remain neutral or to find positive things to say about the drug.

It may be they’re nonplussed by all the hubbub and by the fact that a prescription drug (Xenical) that had not been particularly popular has now obtained FDA approval for over-the-counter use at half the prescription dosage. In fact, such a move could indicate that manufacturers are trying to perform an end run around doctors themselves. (”Doctors don’t seem to be pushing it, so let’s try direct marketing to consumers ourselves.”) And the FDA has lent its imprimatur to the whole proceeding.

Or perhaps we’ve just not caught the right members of the medical community yet. (After all, drug companies do advertise on TV, which may explain the free-for-all we witnessed on Fox.)

But we’ll be happy to point out that there are negatives to a weight-loss program that depends upon not absorbing fats, which is what orlistat, Alli’s active ingredient, is all about. It works by preventing the pancreas from releasing an enzyme (lipase) that enables the breakdown and absorption of triglycerides by the gut. In simple terms, the fat you eat doesn’t get digested and absorbed by your body. It just passes through to be eliminated by the bowel.

Since triglycerides in the blood are one of those things—along with cholesterol—that your doctor is probably trying to get you to reduce, that’s a good thing, right? Well, not exactly. Actually, the high levels of serum triglycerides your doctor is worried about are caused by eating carbohydrates.

And fats, as it turns out, are an important part of the diet. Ever hear the phrase “essential fatty acids?” In case you haven’t, there are essential fatty acids (EFAs) and essential amino acids, neither of which can be produced by the body, which is what makes them essential in the first place. As T.S. Wiley and Bent Formby, authors of the book Lights Out point out, there is no such thing as an essential carbohydrate. So cutting carbohydrates to lose weight actually makes more sense.

What’s more, as these authors point out, fat-soluble vitamins such as A, K, D and E enter the body by hitching a ride with fatty acids in the gut. If you don’t absorb those fatty acids, you may have to do without those fat-soluble vitamins. The information supplied about Alli clearly states that users are urged to take a multivitamin as a part of the accompanying diet regimen. (Much has been made of the manufacturer’s forthrightness in presenting this warning.) What may not be so clear is that the multivitamin likely will have little effect in increasing the absorption of the fat-soluble vitamins if the body is busy not absorbing fats.

We’ve no doubt that Glaxo SmithKline has a winner with Alli. Since the entry cost to try it is around $50, the curiosity factor alone should account for blockbuster sales. But we won’t personally be tempted, given the pill’s health downside and potentially nasty side effects, which include incontinence and get worse from there. (Let’s just say there are worse ways you can be “glued” to your seat.)

We’ll try to cut back on the carbs and treat our bodies to some “burst” exercise. Anybody have a set of kettlebells they’d like to donate?

In the wake of our report on links between atrial fibrillation and bisphosphonate drugs such as Fosamax and Reclast, Health Spectator performed a routine follow-up investigation of the health claims and side effects of this class of drugs. We discovered that, contrary to the majority of reports we had read when researching the initial story, other complications from treatment with bisphosphonates were already known.

Specifically, a condition known as osteonecrosis of the jaw (a condition in which the bone tissue of the jaw literally dies) had previously been linked to taking Fosamax. A check of the Merck website on May 6 showed no mention of this possible complication either under side effects or dosing information. Nevertheless, we found that no less prestigious a group than the New York Academy of Science is sponsoring a conference on bisphosphonates and osteonecrosis of the jaw (ONJ) later this month. In fact, that conference is partially funded by Merck & Co., Inc, Novartis, and Procter & Gamble Pharmaceuticals, the major manufacturers of bisphosphonates.

What’s more, it turns out that the bisphosphonates have been associated with cases of osteonecrosis of the jaw since 2003. That’s when reports surfaced of bisphosphonate-associated osteonecrosis of the jaw (BON) linked to use of Zometa (zolendronic acid) and Aredia (pamidronate). Novartis manufactures pamidronate, as well as zolendronic acid under the names Zometa and Reclast. Zometa is used to treat bone loss in cancer patients and others who are undergoing a more rapid form of bone disintegration than occurs in osteoporosis. Reclast has been approved by the FDA for Paget’s disease and is being considered for treating osteoporosis.

For the most part, early reports of BON were associated with dental work, especially dental work that directly affected the jaw, such as tooth extraction. But then it became apparent that some BON episodes were spontaneous and not the result of dental intervention. The odds of suffering from BON are much greater as a result of dental intervention, so patients who are about to undergo therapy with zolendronic acid (or any bisphosphonate, for that matter) are urged to take care of any essential dental work before beginning treatment.

At this point, the possible complications of treatment with bisphosphonates are unfamiliar to many medical professionals, hence the interest in symposia such as the NYAS educational conference on ONJ and bisphosphonates.