Alzheimer's disease: physicians do not always practice what NICE preaches

The UK government's drug watchdog NICE has received a lot of publicity recently after publishing guidelines restricting the prescription of certain cognitive enhancers for Alzheimer's disease for reasons of cost. However, a recent survey of 181 neurologists by Datamonitor indicates that the NICE cost-benefit methodology may not reflect how the drug is actually used in the clinical setting.

Cognitive enhancers do not treat the cause of Alzheimer's, rather they seek to prevent the cognitive decline associated with it, and fall into two categories: acetycholinesterase inhibitors (AChEIs) including Aricept (donepezil), Exelon (rivastigmine) and Razadyne (galantamine), or the NMDA antagonist memantine, which is branded as Namenda and Ebixa in the US and Europe respectively.

The National Institute for Clinical Excellence (NICE) published guidelines in the UK in November of 2006, stating that AChEIs are recommended for moderate severity AD only, and that memantine is not recommended for any disease severity. Following the publication of these guidelines, stakeholder groups reacted angrily, and much of the media has condemned the NICE for suggesting that AD suffers should not be prescribed drugs which only cost around GBP2.50 a day.

NICE in practice

However, there is evidence to suggest that the guidelines do not necessarily reflect clinical practice. In the previous NICE guidelines published in 2001, AChEIs were not recommended for severe severity AD patients. Despite this, and a lack of marketing license, Datamonitor's neurologist survey showed that 54% of severe AD patients in the UK currently receive an AChEI (either alone or with memantine) as a first-line therapy. This not only indicates that neurologists are willing to prescribe AChEIs off-label, but that Aricept's recent approval for severe severity AD may not stimulate significant increased sales revenue.

In addition, Datamonitor found that 2.2 times more AD patients receive AChEI + memantine combination therapy than memantine monotherapy in the UK. The survey also indicated that the single most common second-line therapy was Aricept + memantine. NICE evaluated the cost-effectiveness of memantine and AChEI's separately, therefore, Datamonitor believes that the calculations do not always represent how the drugs are actually used in the clinic.

This finding suggests that pharmaceutical companies marketing AD drugs may benefit from further clinical trials investigating the benefit of AChEI + memantine combination therapy. Although this may be a risky strategy, as it is entirely possible that the combination therapy approach may be less cost-effective than monotherapy.

Positive future on horizon

The current treatments for AD are merely symptomatic, enhancing or rescuing some cognitive function. The efficacy of these treatments is modest, with one meta-analysis of AChEI clinical trials indicating that only 9% of patients significantly respond to treatment1. In addition, little scientific evidence exists to indicate that cognitive enhancers prolong life.

The future however, could be brighter for AD patients. Two potentially disease modifying drugs, Neurochem's Alzhemed and Myriad Genetics's Flurizan, are currently in phase III development. Their modes of action are centered on inhibiting the toxic beta-amyloid cascade believed to be responsible for the neuronal cell death found in AD.

Although it is difficult to assess until the current large-scale clinical trials are complete, hopefully these new drugs will prove to be significantly effective at prolonging cognition, and perhaps even prolong life. If that was the case, a much higher cost could be justified by the pharmaceutical companies when challenged by pharmacoeconomic bodies such as the UK's NICE.

Related research:

 Stakeholder Insight: Alzheimer's Disease - Prescribing trends indicate that neurologists are not adhering to guidelines
 Stakeholder Opinions: Parkinson's Disease - Review of Key Commercial Opportunities in the Symptomatic Treatment Market
 Stakeholder Insight: Major Depressive Disorder - Duloxetine - Fulfilling An Unmet Need?

Pfizer says HIV drug suppresses virus
A new study has revealed that Pfizer's HIV drug maraviroc achieved twice the levels of virus suppression compared to other treatments and suggests the drug could work in patients where all other therapies have failed.
Maraviroc is part of a class of drugs known as CCR5 inhibitors and works in a new way to existing therapies. The drug blocks the virus' entry to cells T cells, a type of white blood cell, so that the HIV virus can no longer replicate.

The drug was examined in two phase III trials. The first trial that showed 60.4% of those who took maraviroc achieved a level of less than 400 HIV copies per milliliter of blood, compared to 54.7% on a once-daily dose and 31.4% on background therapy.

The second trial found that 61.3% of twice-daily maraviroc patients achieved target HIV levels, compared with 55.5% on once-daily dose and 23.1% treated with other drugs.

"HIV therapies have, for so long, focused on people needing drugs for their initial treatment. But there is a huge and growing number of people who've failed on first and second-line therapies, who need other drugs later on", said Michael Carter, an HIV expert from the UK's National Aids Manual.

Related research

Pipeline Insight: HIV - Extending treatment options

Commercial Insight: HIV - Change of guard

An expert panel has recommended Sanofi-Aventis' avian flu vaccine to the FDA
Despite concerns over lack of efficacy, Sanofi-Aventis' experimental vaccine against the H5N1 influenza strain has become the first such product to receive backing from an FDA advisory panel. However, the vaccine may face significant competition in the long-term from several other companies developing H5N1 vaccines using more advanced adjuvant technology.
The vaccine was shown to trigger a response in only 45% of patients receiving the highest dose during clinical testing, which falls short of the agency's standards. While the advisory panel has acknowledged the vaccine's shortcomings, their backing of vaccine was based on the benefits of having a licensed vaccine against a potential influenza pandemic as opposed to having no vaccine at all.

In the US alone, there are an estimated 2550 million cases of influenza per year, leading to 150,000 hospitalizations and 30,00040,000 deaths. However, there are grave concerns at the health and economic devastation that could be caused by the influenza A subtype H5N1. It has spread rapidly from Asia to Africa and Europe, and although there have been no reported human-to-human transmissions, this threat alone has driven demand for proactive development of a suitable vaccine.

GlaxoSmithKline, Baxter International Inc, and Novartis AG are also developing testing H5N1 influenza vaccines. However, they have focused development on increased efficacy through novel adjuvant technologies.

Novartis' alternative strategy is to have authorization in place that can be changed rapidly once the responsible pandemic virus strain has been identified and incorporated. Focetria has recently received EU recommendations for marketing authorization from the Committee for Medicinal Products for Human Use.

Sanofi's first-to-market status may be a short-term advantage, but adjuvant use will reduce antigen volume requirements. Sanofi's manufacturing capacity may initially offset this disadvantage, but competitor products are likely to be more cost effective to produce, leaving Sanofi reliant on developing a similar adjuvant delivery system to compete profitably.

Related Research

Pipeline Insight: Therapeutic Cancer Vaccines - A turbulent path from bench to bedside

Stakeholder Perspectives: Influenza Vaccines - Flying back Into Flu

Abbott cleared to market Crohn's drug in US
Abbott Laboratories has received FDA approval to market Humira as a treatment for reducing the symptoms and inducing clinical remission in adults with Crohn's disease who have had an inadequate response to conventional therapy.
Humira is also indicated for reducing the signs and symptoms and inducing clinical remission in these patients if they have also lost response to or are intolerant to infliximab, the only other approved biologic for treatment of Crohn's disease.

Crohn's disease is a serious chronic, inflammatory disease of the gastrointestinal tract. Common symptoms of Crohn's disease include diarrhea, cramping, abdominal pain, weight loss, fever, and in some cases, rectal bleeding.

Humira also comes with the strongest possible warning because the drug has been associated with serious infections, sepsis, tuberculosis and opportunistic infections, including fatalities.

This approval establishes Humira as the first and only self-administered biologic for the treatment of Crohn's disease. Crohn's disease is the fourth FDA approval in immune-mediated diseases for Humira.

"The approval in Crohn's disease extends the reach of Humira beyond rheumatology and dermatology to an underserved patient population in gastroenterology," said Eugene Sun, vice president, Global Pharmaceutical Clinical Development at Abbott.

"In addition to rapid and sustained response, Humira offers patients with moderate to severe Crohn's disease the convenience of self-injection in the comfort of their home."

Related research

Abbott: PharmaVitae Profile

Commercial and Pipeline Insight: Inflammatory Bowel Disease-Competition Increases for the Biologics

Strategic Perspectives: Inflammatory Bowel Disease - The Rise of Remicade

The FDA has approved Cymbalta to treat generalized anxiety disorder (GAD).
Eli Lilly's Cymbalta has gained the approval of the FDA for use in patients with GAD. The expanded indication is positive news for Cymbalta, which is already approved in the US for the treatment of major depressive disorder and the management of diabetic peripheral neuropathic pain.
Cymbalta (duloxetine HCl) is serotonin and norepinephrine reuptake inhibitor (SNRI), which is a class of drugs that is primarily indicated for the treatment of depression, but may also be prescribed for a variety of other mental health issues, including panic, anxiety and eating disorders.

The FDA's approval of Cymbalta to treat GAD as well as depression and neuropathic pain is based on three randomized, double-blind studies in non-depressed adults with the disorder. The results of these studies have shown that 46% of patients treated with Cymbalta had improved anxiety-related symptoms as compared to 32% of patients treated with a placebo. In addition, 46% of patients who took Cymbalta experienced an improvement in their abilities to perform everyday activities related to work, home and social situations as compared to 26% of patients in the placebo group.

With sales in 2006 of $1.316 billion, up from $680 million in 2005, Cymbalta is a promising driver of growth for Lilly. Despite the strength of this drug the market, it has not been without its opponents. Detractors point to both the exponential growth in the number of prescriptions for SNRIs in recent years and the link that has been made between these drugs and a potential for increased risk of suicide in children and teenagers. Cymbalta is not approved for use in pediatric patients.

It is estimated that approximately 6.5 million Americans are diagnosed with GAD each year. Many of those diagnosed will seek treatment in the form of cognitive behavior therapy. However, because of the chronic nature of the disorder and because GAD has been linked with irregular levels of neurotransmitters in the brains of those affected, many individuals find they are better able to manage the disorder with the help of pharmaceutical drugs.

Cymbalta's expanded indication is good news for adult patients and prescribers who are looking for additional pharmaceutical options for the treatment of generalized anxiety disorder and for Eli Lilly, which is counting on the drug to prove to be a safe and effective treatment for a wide range of mental and physician disorders related to serotonin and norepinephrine absorption.

Related Research

Neuropathic Pain - A Plethora of Patient Segmentation and Product Differentiation Opportunities

Bipolar Disorder - New treatments for bipolar depression set to drive near-term growth

GSK hay fever drug relieves symptoms
A GlaxoSmithKline allergy medicine currently under review by the FDA, was effective and well-tolerated in treating a range of nasal allergy symptoms such as congestion, sneezing, itchy and runny nose, according to phase III clinical studies.
In two separate phase III studies, fluticasone furoate nasal spray (FFNS) was more effective than placebo in relieving both the nasal and eye symptoms of patients 12 years and older with seasonal allergic rhinitis, commonly known as hay fever.

One additional phase III study among individuals with perennial allergic rhinitis (year-round nasal allergies) found FFNS to be more effective than placebo in relieving nasal symptoms. Moreover, the symptom-relief lasted 24 hours in all three studies.

"These are the first two prospectively-designed phase III studies to demonstrate consistent and significant improvement in eye-related allergy symptoms with an intranasal steroid," commented lead investigator William Lumry, Asthma & Allergy Specialists, Dallas.

Related Research

GlaxoSmithKline: PharmaVitae Profile