Pipeline - Pharmaceutical Executive


Rays of Light

Pharmaceutical Executive

LIQUID CONDOMS: Gilead´s Tenofovir Puts HIV Protection in the Hands of Women
Merck ambitiously pitted MK-0518 in Phase III trials against Bristol-Myers Squibb market leader Sustiva (efavirenz), and 24-week data showed equal efficacy in both patients new to treatment and those struggling with resistant virus.

But given the disappointment of last year's pipeline darlings, the CCR5 entry inhibitors, a big question mark still remains. Plus, the drug's twice-daily dosing requirement poses a risk to patient adherence—and the development of HIV resistance. In the brave, new world of the once-daily, single-pill HIV treatment, introduced last summer as Atripla, MK-0518 may need to add convenience to muscle to elbow its way to number one.

Eash expects the first integrase inhibitor to get FDA approval by late 2008, and predicts that the class (Gilead has a Phase II candidate, followed by a GSK/Shionogi in Phase I) will break the blockbuster barrier by 2012. –WA

BRAIN FLOSS: Alzheimer's Meds Pick at the Root

Alzhemed Neurochem

TARGET INDICATION Alzheimer's disease

Canadian drug manufacturer Neurochem is slated to release the first disease-modifying drug for the treatment of Alzheimer's in 2008. Alzhemed (tramiprosate) is a beta-amyloid aggregation inhibitor that helps prevent molecules of amyloid from binding to each other and forming plaque that causes memory failure.

"The drugs on the market today address the symptoms of Alzheimer's, but aren't addressing the cause of neuronal death," says Andrea Witt, CNS analyst at Decision Resources. Alzhemed and other pipeline hopefuls may put the brakes on beta-amyloid accumulation in the brain, which causes neuronal death and Alzheimer's symptoms. "If a drug can prevent the build up of plaque, we have the potential to slow the onset and cognitive decline in Alzheimer's patients," says Witt. "This would be the first drug to hit the market that has an effect on the underlying cause of the disease."

Alzhemed has shown limited efficacy in Phase II trials, but has good tolerability levels in patients. Drug sales are expected to be between $2 and $3 billion by 2015. –GEORGE KORONEOS

TC-1734 AstraZeneca

TARGET INDICATION Cognition dysfunction

AstraZeneca has caused a stir with its nicotinic acetylcholine antagonist, TC-1734 (ispronicline), likely to be the first drug available to treat cognitive dysfunction associated with aging, schizophrenia, and other diseases. The drug, which AstraZeneca licensed from Targacept, shares the same method of action as cigarette-smoking addiction.

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"Compounds like TC activate nicotine receptor subtypes in the brain," says Jerry Buccafusco, professor of pharmacology and toxicology at the Medical College of Georgia. "By doing so they try to get some of the beneficial effects of nicotine in terms of cognition, without the cardiovascular side effects or addiction."

In Alzheimer's, the cells that produce the neurotransmitter acetycholine begin to die off, causing increasing deficits in cognition. Most existing Alzheimer's drugs target the enzyme that breaks down acetycholine. Nicotinic medication bypasses those neurons and acts directly on the acetycholine receptors, which could prevent the neurons from dying in the first place. Current medications can improve cognition performance in a certain number of people, but that benefit declines if they stop taking the drug. TC-1734 and others in development may not only manage symptoms, but arrest the disease.

Ispronicline also offers benefits in schizophrenia. "It's not so much addressing schizophrenia symptoms, as it is the cognitive impairment in schizophrenia," says Andrea Witt, CNS analyst at Decision Resources. It binds "to the nicotinic acetylcholine receptors and enhances cognition."–GK

SILVER BULLET: Oncology Drugs Hit Many Targets

Tasigna Novartis

TARGET INDICATION Chronic myeloid leukemia
DEVELOPMENT Preregistration

For patients with chronic myeloid leukemia, Gleevec (imatinib) has proven to be something of a wonder drug, with five-year survival rates surpassing 85 percent. But Novartis believes there is room for improvement, and is working to develop a second-generation version even more selective in targeting the cancer-causing Bcr-Abl gene and its mutations. Phase II results suggest that Tasgina (nilotinib) might be effective in 46 percent of Gleevec-resistant patients—potentially with fewer side effects. Like Gleevec, which is also approved for six additional indications, the drug's mechanism of action might mean that its approved indications only scratch the surface. Tasigna "has well over $1 billion in market potential," says Heather Brilliant, an analyst at Morningstar. One wrench in earnings could be Sprycel (dasatinib), Bristol-Myers Squibb's drug that targets the same gene and was approved in June. Sprycel nabbed sales of $11 million in the first quarter of 2006. –BH

Tykerb GlaxoSmithKline


6 Oncology Drugs to Watch
GSK's Tykerb (lapatinib) was the talk of the American Society of Clinical Oncology meeting this year. Phase III data showed that the drug could double the time of progression of HER-2 positive breast cancer compared with chemotherapy alone, and might also prevent the brain metastases that are associated with this type of cancer.

While Tykerb is being tested in women who are resistant to Genentech's blockbuster drug Herceptin (trastuzumab), the two drugs might one day compete head-to-head. Tykerb has the advantage of being a small molecule—so it can be given in a more patient-friendly pill form, rather than through an infusion. "What we're seeing in the field is efforts to move toward drugs that can be delivered orally," says David Johnson, MD, director of hematology/oncology at Vanderbilt University Medical Center. "Hopefully we'll be seeing more of these in the future."


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