Personalized medicine has been hailed for years as the medicine of the future. The future has arrived, in the form of trial successes with a pharmacogenomic test for determining optimum drug treatment for individual cancer patients, and with monoclonal antibody and anti-angiogenic drugs for:

• Lung cancer,
• Colon cancer and asthma,
• Thyroid cancer, and even
• A vaccine against one form of leukemia. We need these efforts, given that 76 million baby boomers in the US alone are reaching the age at which cancer rates start rising. If money talks truth, then a $15 billion increase in the value of just one biotech firm following promising trial results for just one of these drugs augurs well for those among the 76 million who need and can afford them, and for the development of similar drugs for other cancers and diseases.

A vaccine for malaria has also passed phase I safety trials, and the Aussies are hot on the trail of a melanoma cure, among other achievements. Parkinson’s is showing signs of succumbing to gene therapy, and Viagra to competition.

A less esoteric therapy — a superpill of common drugs — could have an even bigger impact on healthcare overall by preventing 80 percent or more of strokes and heart attacks.

Finally, there’s therapeutic help for stressed parents of cancer-stricken children, in the form of an artificially intelligent software robot.

Pharmacogenomics for Cancer

A new genetics-based cancer screening test helps prescribe the optimum drugs for treating cancer in an individual, and predicts the patient’s long-term prognosis. Promising preliminary results are being followed up by three large-scale trials, and the screening tests could be available to physicians within a year. Drug companies could also use the technology, to determine which patients are most likely to benefit from experimental drugs.

The technology determines which genes are activated in a specific tumor and helps make treatment decisions based on that information. In one small study, the technology revealed genetic evidence that could help determine which lung-cancer patients would be most likely to respond to the just-approved new-generation cancer drug Iressa. Iressa shrinks tumors in only ten percent of patients tested, but knowing who is likely to respond to the drug could double the success rate.

The technology can also be used to analyze the tumor specimens that have been routinely collected and stored following surgery at virtually every hospital in the country for 20 years or more. By comparing the patient’s disease progression (obtained from medical records) with what the tumor looked like at the time of diagnosis, the efficacy of their treatment can be assessed.

Reference: Jacobs, Paul (2003). “Biotech start-up takes step toward personalized cancer treatment.” Mercury News, June 3.

Promising Lung Cancer Drug

Following the success of its angiogenesis-based colon cancer drug Avastin, which extended trial patients’ lives by five months, Genentech intends to speed up the normal, slow, process of individually testing and awaiting approval of experimental cancer drugs by testing combinations of them in new tumor types. The hope is to replace chemotherapy with a less toxic but more effective cocktail of genetic drugs. Preliminary results of a small lung-cancer trial combining Avastin with another experimental drug, Tarceva, are promising. (Tarceva is similar to Iressa.) Used alone, Tarceva has shrunk tumors in roughly ten percent of lung cancer patients, while Avastin has barely been effective at all. Combined, however, the two drugs shrank tumors in 25 percent of 12 patients with advanced lung cancer and stabilized them in another 40 percent. Genentech also has Tarceva with Avastin in colon cancer trials, and with Herceptin in advanced breast cancer.

The experimental cancer drug Alimta, originally designed only for mesothelioma, proved as effective as Taxotere as a second-line treatment for non-small cell lung cancer as well. Survival was largely the same, at about eight months, for both Taxotere and Alimta patients, but Alimta caused far fewer side effects among the 571 lung cancer patients studied. Severe white blood cell loss occurred in five percent of patients taking Alimta, versus 40 percent of patients on Taxotere. Serious adverse drug effects were noted in ten percent of patients given Alimta, versus 24 percent of Taxotere patients. However, in the study, Alimta was supplemented with vitamin B-12 and folic acid.

References: Langreth, Robert (2003). “Genentech’s Next Move.” Forbes, June 10; Swiatek, Jeff (2003). “Lilly’s drug for cancer ‘exciting’.” Indianapolis Star, June 3.

Smart Bombs for Cancer and Asthma

“There are real grounds for hope for cancer sufferers” said a senior executive of a biotechnology firm with regard to the relatively new class of monoclonal antibody drugs spearheaded, in the case of cancer, by Herceptin (for some breast cancers) and Rituxan (for lymphoma). The grounds for hope are not just therapeutic for the patient, but financial for the drugmakers: those two drugs alone are approaching sales of $2 billion a year, while Avastin, an experimental drug for colon cancer and possibly other tumors, is showing such promise that its maker’s market cap increased by $15 billion within days of an announcement of positive trial data. The financial success is causing a surge of activity in cancer drug development. Human Genome Sciences is developing nine potential cancer treatments. ImClone’s cancer drug, Erbitux, is back in favor following a bad start.

Monoclonal antibodies represent one of the first applied triumphs of the HGP. They are essentially artificial antibodies, proteins that can be targeted directly at tumor (and other) cells. They appear to be less toxic than chemotherapy, to which they might find their niche as adjuncts. Alternatively, and preferably from a therapeutic perspective, they might be able to hold tumor growth in check indefinitely, without chemotherapy. But from a financial perspective, unless the current $10-50,000 annual per-patient cost of the new treatments can be drastically reduced, turning cancer into a chronic disease could break the back of a health system already facing bankruptcy.

Another monoclonal antibody drug, Xolair, received FDA approval in June. It can stop asthma attacks before they start, and has potential for treating hay fever and food allergies as well. No less a personage than the president of the American College of Allergy, Asthma and Immunology called it “the most dramatic, innovative drug that we’ve seen brought on the market in the last 30 years.” However, FDA-imposed restrictions on its use limit the potential users to about 500,000 of the estimated 17 million asthma patients in the United States. It must be injected once or twice a month and costs $5-10,000 a year.

A clinical trial patient reported that Xolair not only helped his asthma but allowed him to touch his cat and eat seafood without suffering the severe allergic reactions he gets without the thrice-weekly Xolair injections. Sadly for him and perhaps his cat, he cannot afford the treatment now that it is on the market. Given the risks that trial patients take for the benefit not only of themselves but of others, one would expect that a civilized society could find a way to eliminate such unfairness.

References: Gillis, Justin; and Michael Barbaro (2003). “For Biotech Firms, Outlook Brightens on Cancer Drugs.” Washington Post, June 23, page A01. ; Pollack, Andrew (2003). “F.D.A. Clears Asthma Drug That Short-Circuits Attacks.” New York Times, June 21. (URL lost.)

Thyroid Cancer Drug

Oxigene has received FDA fast-track status from the Food and Drug Administration for an anti-angiogenisis drug to treat a hitherto untreatable form of thyroid cancer by cutting off the blood supply to the tumor. In a Phase I (safety) trial of the drug three years ago, five of nine patients with advanced anaplastic thyroid cancer showed some sort of positive effect, and one of them has been without symptoms ever since. The drug is now in Phase (efficacy) II trials.

Reference: Forelle, Charles (2003). “Oxigene Receives ‘Fast Track’ Status From the FDA for Its Thyroid Drug.” Wall Street Journal, June 4.

Cancer Vaccine

Antigenics’ AG-858 cancer vaccine has achieved positive early results in patients with chronic myelogenous leukemia (CML). The vaccine programs the immune system to recognize a “heat-shock protein” molecule present in many kinds of cancer. The vaccine must be laboriously tailored to the specific molecular biology of the individual patient’s cancer, but of eight patients tested so far, seven have “demonstrated a response,” according to Forbes correspondent Matthew Herper, though it is too soon to claim victory.

Reference: Matthew Herper, (2003). “Cancer Vaccine Finds A Proving Ground.” Forbes, June 3.

Malaria Vaccine

Researchers have made a vaccine for malaria by injecting human volunteers with one scrap of DNA and then another in a poxvirus. The vaccine tricks the immune system into producing enough cells to attack malaria. It worked well in Phase I safety trials.

Reference: Clarke, Tom (2003). “Malaria Vaccine Gets a Boost.” Nature, May 26 (citing McConkey, S. J. et al. Enhanced T-cell immunogenicity of plasmid DNA vaccines boosted by recombinant modified vaccina virus Ankara in humans. Nature Medicine, Advance online publication DOI:10.1038/nm881, 2003.)

Emerging from Down Under

Australian organizations:

• Are conducting human trials of a world-first detection method for detecting deep vein thrombosis;
• Are further testing a melanoma treatment that has already cured several terminally ill patients;
• Have discovered a way of regenerating the immune system of leukemia patients by blocking the body’s sex steroids, or hormones.Reference: Bachelard, Michael, and Scott Emerson (2003). “Booster shot for biotech.” (Source lost), June 24.

Gene Therapy for Parkinson’s

Levodopa, a treatment for Parkinson’s disease, eventually stops working. A new gene therapy could maintain the drug’s effectiveness over much longer periods than at present, and that would have a major beneficial impact on the lives of advanced Parkinson’s sufferers. Over a three and a half year period in which a virus carrying an enzyme-producing gene called AADC was injected into the brains of monkeys with a (chemically induced) severe form of the disease, the enzyme continued to transform levodopa into dopamine, the neurotransmitter whose absence is the hallmark of the disease. There were known no adverse effects. A small-scale human trial could begin in late 2003. Clinical trials involving another gene, GDNF, that could help slow or halt the disease at an earlier stage, could begin within three years.

Reference: Jonietz, Erika (2003). “Gene Therapy Advances on Parkinson’s.” Innovation, July/August.

Viagra Competition

In phase I clinical trials, an erectile dysfunction drug called PT-141 produced sustained erections lasting up to three hours. Some patients who didn’t achieve an erection taking Viagra did with PT-141. Unlike Viagra, PT-141 is administered via nasal spray, works with or without visual or tactile stimulation, and is safe for people who take nitrates for heart conditions. PT-141 will also be tested in women later this year.

Reference: Philipkoski, Kristen (2003). “Impotence Drug Takes on Viagra.” Wired News, June 17.

Superpill

An international team of researchers proposes that a “Polypill” containing six active components — aspirin, folic acid, a cholesterol-lowering drug and three drugs to lower blood pressure at half the normal dose — could prevent 88 percent of heart attacks and 80 percent of strokes, and would therefore have a greater impact on the prevention of disease in the Western world than any other single intervention. About one in three people would gain an average of 11-12 years of life without heart attack or stroke. The Polypill could be inexpensive, safe, have few side-effects, and be sold without prescription, they reckon.

Reference: Horton, Julia (2003). “Medics unveil ‘wonderpill.’” Edinburgh Evening News, June 26.

Bot Therapy

In a clinical trial of “Carmen’s Bright IDEAS” (CBI) developed by the University of Southern California and funded by the National Cancer Institute, animated cartoon-like software robots or “bots” endowed with artificial intelligence helped mothers of children with cancer cope with the stresses of caring for them.

The bots are familiar with an established problem-solving method for stressed people called IDEAS (‘Identify a solvable problem, Develop possible solutions…”). Their responses are not canned, but created on the fly by complex and sophisticated AI algorithms, and are based on the specifics of the situation at any given moment.

The real mother controls the interactions of her surrogate bot mother with her two sick child bots and a counselor bot. Essentially, the real mother acts out her decisions through the mother bot, and the other bots respond in accord with IDEAS’ principles. If the real mother begins to make the mother bot respond positively to the other bots’ counseling, then the system is deemed to have succeeded in teaching the real mother best coping skills.

The researchers concluded from the 26-mother trial that “overall the results were uniformly positive.” A next step may be to create a version of CBI for handhelds, so that mothers can carry “a counselor in a purse or pocket.”

Reference: University Of Southern California (2003). “Robo-thespians Help Mothers Of Kids With Cancer.” ScienceDaily Magazine, June 12.