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PharmaNews Bytes: Selected September press releases from the pharma/biotech sector

Posted on: 17 Sep 04


LeadDiscovery's intelligence service, DailyUpdates has evolved as a key tool to help all in the drug development sector keep track of breaking journal articles, press releases and pharmaceutical reports. Pharma NewsBytes features selected press releases recently featured on DailyUpdates and offers the reader a leisurely stroll through the past few weeks of activity from within the pharmaceutical industry.

LeadDiscovery's intelligence service, DailyUpdates has evolved as a key tool to help all in the drug development sector keep track of breaking journal articles, press releases and pharmaceutical reports. Pharma NewsBytes features selected press releases recently featured on DailyUpdates and offers the reader a leisurely stroll through the past few weeks of activity from within the pharmaceutical industry.

Selected press releases - September 1st-14th

  • News on asthma therapeutics presented at the European Respiratory Society [more]
  • Stroke prevention - good and bad news [more]
  • News from the European Association for the Study of Diabetes [more]
  • Long-awaited FDA decisions on pain therapeutics [more]
  • News listed on DailyUpdates September 1st onwards[more]

News on asthma therapeutics presented at the European Respiratory Society: From 1980 to 1996, the number of Americans afflicted with asthma more than doubled to almost 15 million, with children under five years old experiencing the highest rate of increase. The steady rise in the prevalence of asthma constitutes an epidemic, which by all indications is continuing. Even if rates were to stabilize, asthma would continue to be a profound public health problem, each year responsible for 9 million visits to health care providers, over 1.8 million emergency room visits, and over 460,000 hospitalizations. As well as placing a considerable burden in terms of direct medical costs, asthma is one of the leading causes of work or school absenteeism.

Paralleling the dramatic growth in its incidence, asthma is driving one of the most rapidly growing global therapeutic markets. The impact that increased incidence is having on therapeutic market values is further increased by a considerable degree of under-treatment of asthma. Global revenue for 2001 from asthma therapies has been reported by some to be as high as $11.7 billion and up until recently annual growth rates of 10-15% have been reported.

In terms of numbers and health care expenses the chronic obstructive pulmonary diseases (COPD), chronic obstructive bronchitis and emphysema, are event more serious than asthma. World-wide, 600 million people suffer from these disease with some three million dying as a result each year. COPD is caused by chronic respiratory inflammation, proteolytic breakdown of airway tissue and consequent loss of elastic recoil in the lungs. This serious healthcare problem is paralleled by global sales of around US$2.8 billion which will increase in value significantly over the next decade. This will be driven by the aging population, new approvals and increased awareness.

Since the anti-asthmatic market is well served by existing therapies, such as the beta2-agonists and corticosteroids which can treat 95% of asthma patients competition within the anti-asthmatic market will grow increasingly intense. Consequently, to attain commercial success, pipeline products need to offer significant advantages over currently marketed therapies. In stark contract to the situation for asthma, therapeutic options for the treatment of COPD are limited and this represents an unmet market.

In the short-term the lack of effective oral therapies in the pipeline for both asthma and COPD means that inhalation will remain the primary mode of delivery. Advair, GlaxoSmithKline's blockbuster was initially approved as an asthma therapeutic but was used off-label for the treatment of COPD. However Advair, a combination of the corticosteroid fluticasone and the beta2-agonist bronchodilator, salmeterol has now been approved for the treatment of COPD which will see prescribing rates rise above off-label levels contributing to growth in the market. The asthma/COPD market will increase by 35% to over $18 billion by 2011 largely due to the success of inhalation therapies.

Although the $3.9 billion in Advair revenue dwarfs its nearest competitor, AstraZenecca's Symbicort (annual sales of $549 million) the annual meeting of the European Respiratory Society in Glasgow heard how GlaxoSmithKline's dominance of respiratory medicine is being challenged by a raft of new drugs.

The looming threat to Advair and negative sounds coming from analysts resulted in shares in GSK, which generates 21% of its sales from respiratory drugs, falling 1.6%. Analyst Anthony Colletta said he had reduced his forecast for GSK sales in 2010 by $1.1 billion due the challenge posed to Advair by AstraZeneca Plc's Symbicort and two new therapeutics for COPD, Spiriva and Daxas.

At the meeting AstraZeneca presented new data that it said reinforced the benefits of Symbicort over Advair and which analysts believe will strengthen the product's appeal when it finally goes on sale in the United States. Symbicort, while widely available in Europe, is not yet approved in the US. But a filing for marketing approval is expected to be submitted to the FDA in the first half of 2005. Analysts at Lehman Brothers said Symbicort would be a key mid-term focus for management and investors in coming months and would be in the spotlight at AstraZeneca's annual business review day on October 6.

Like Advair, AstraZeneca's drug combines a bronchodilator for short-term asthma relief with a corticosteroid to treat inflammation, but patients are able adjust their dose of Symbicort according to how they feel (click here for a full analysis of combination therapies). That flexibility has prompted rapid take-up in Europe, where the drug has captured more than a quarter of the market within three years. By 2010 Dresdner expects Symbicort to rake in $3.1 billion, significantly closing the gap on Adavir which is forcast to be generating $7.7 billion.

Providing further competition to Advair, Boehringer Ingelheim's recently launched anticholinergic Spiriva is the first specific drug for COPD and analysts forecast sales of $3.3 billion in 2010. PDE-4 inhibitors will be the next novel drug class to reach the respiratory market, with the launch of roflumilast (Daxas) expected to generate sales of $2 billion [more on this story]

Further news from European Respiratory Society emerged surrounding Novartis' Xolair which was reported to effectively control even very severe cases of asthma.

This new data will be used by the Swiss healthcare group to strengthen its case with European regulators for the drug to be approved as a treatment for people with uncontrolled, and sometimes life-threatening, asthma, a sub-type of this conditions that is largely unmet. A 419-patient study showed that Xolair reduced the rate of clinically significant asthma attacks by 26% during 28 weeks of treatment. Xolair, the first biotechnology treatment for asthma, was developed by Novartis, US biotechnology group Genentech and Tanox Inc and was approved in the United States last year making it the first biologic to be approved for asthma (click here for an evaluation of biologic therapies for inflammatory & autoimmune disorders). It was filed for EU approval in July. Xolair is a monoclonal antibody (click here for an evaluation of therapeutic antibodies) that works by blocking IgE thus treating the underlying cause of asthma triggered by allergies rather than the symptoms that inhaled corticosteroids address. However, it is less convenient then inhalers because the drug has to be injected. In the US, it is approved for treating moderate to severe asthma but Novartis is seeking approval in Europe for a narrower use among patients worst affected by asthma. Around 300 million people in the world have asthma, of whom an estimated 15 million have severe or life-threatening forms of the disease. Xolair generated US sales of $30 million in the first quarter of this year [more on this story]

Following the success of Xolair a number of other biotechs have focused on the development of antibody therapeutics in the respiratory tract arena. On Sept 8 one such company, Cambridge Antibody Technology, announced that it will be starting a Phase I clinical trial of CAT-354, a human anti-IL-13 monoclonal antibody, which is a potential treatment for severe asthma.

IL-13 is one of the molecules singled out as a target for future asthma therapeutics in LeadDiscovery's recent report "Asthma Therapeutics: New treatment options and emerging drug discovery targets". The Phase I trial is a placebo-controlled, rising single intravenous dose study of CAT-354 and will take place in the UK at the Marix Drug Development Clinical Research Centre. The objectives of the trial will be to study the safety, tolerability and pharmacokinetics of CAT- 354. Patient enrolment is expected to commence shortly and the results of the trial are likely to be available during the second quarter of 2005. Dr. David Glover, CAT's Chief Medical Officer, comments: "The initiation of this clinical trial represents a further milestone in the development of CAT as a biopharmaceutical company. CAT-354 is the fourth human monoclonal antibody that we have taken into clinical trials ourselves and makes a total of 11 human antibody drug candidates discovered using our technology that have entered clinical development. We are very optimistic about CAT-354 as a potential treatment for severe asthma." [more on this story]

Stroke prevention - good and bad news: About 700,000 Americans suffer a new or recurrent stroke each year usually due to atherosclerosis in the carotid/vertebral arteries. Recovery from stroke is unpredictable and rarely complete and consequently 15-30% of ischemic stroke victims are permanently disabled and 20% require prolonged institutional care. Stroke survivors are at high risk of suffering a further stroke - compared with the population as a whole, their risk of stroke is multiplied 15-fold.

After age, hypertension is the most powerful risk factor for stroke. Hypertension is a relatively well served therapeutic field, with a range of well-tolerated drug classes (click here for a full analysis of current and emerging classes of antihypertensives). Despite this, the majority of patients are not controlled. Results of large-scale outcome studies in the last decade suggest there is no longer a gold standard therapy for hypertension. Over recent years the angiotensin II receptor antagonists, or 'sartans', have been the fastest-growing antihypertensives with sales of losartan hitting $1.4 billion in the first half of 2004. According to the analysts DataMonitor the need for antihypertensives to do more that just lower blood pressure may confer a market advantage and effective protection against stroke represents an ovious opportunity.

In a press release circulated August 31 the established antihypertensive agent TEVETEN (eprosartan) was reported to offer effective protection against cerebrovascular and cardiovascular events in hypertensive patients with a previous stroke, over and above that offered by blood pressure reduction offering potential market opportunities for this antihypertensive.

Initial results from the landmark MOSES(1) study, presented by Professor Joachim Schrader at the XXVI Congress of the European Society of Cardiology in Munich, showed that blood pressure was equally well controlled when hypertensive patients with a history of stroke were treated with either TEVETEN-based or nitrendipine-based therapies. However, there was a significant reduction of 20% in the primary endpoint (total mortality and total cardiovascular and cerebrovascular events) in the TEVETEN group. In addition, there was a significant reduction of 25% in the recurrence of stroke and associated disease (transient ischemic attack and prolonged reversible neurological deficit, and a significant reduction of 30% in first-time cardiovascular events in patients treated with TEVETEN.

Other angiotensin-II receptor antagonists have previously demonstrated cardio- and cerebroprotective effects in patients at risk of stroke. However, earlier studies focused on patients who, although at risk, have not yet had a stroke. These studies helped to establish the value of antihypertensive treatment in primary stroke prevention, but until now there were few data on the effectiveness of these drugs in preventing recurrent stroke. MOSES is the first study to specifically compare the outcomes of alternative antihypertensive treatment in patients with a history of stroke. The calcium channel blocker nitrendipine was chosen as the comparator agent because of its success in the Syst-Eur study(2) where treatment reduced the risk of stroke by 42% in elderly patients with systolic hypertension. In the MOSES study, both nitrendipine and TEVETEN produced impressive reductions in blood pressure, with approximately 75% of patients in each group reaching the target blood pressure as determined by ambulatory blood pressure monitoring. Since both agents produced similar reductions in blood pressure, the reduced incidence of cerebrovascular and cardiovascular events in patients receiving TEVETEN indicates that these benefits are achieved independently of blood pressure reductions. [more on this story]

Not such good news for stroke sufferers was announced on Sept 9th when an FDA review of AstraZeneca's Exanta questioned the experimental drug's effectiveness as a stroke treatment and faulted the company's plan to manage possible toxic side effects.

The news, which came a day before a panel of outside experts met to discuss whether to recommend Exanta for approval by the FDA, shook widespread confidence among investors in the potential blockbuster. The company may have been "too liberal" in assessing the effectiveness of Exanta against the standard anticlotting treatment warfarin, according to FDA staff comments. Several reviewers expressed concern over AstraZeneca's decision to compare Exanta to warfarin rather than a placebo in some studies. Exanta is the first new anticoagulant pill since warfarin was introduced 60 years ago. A notoriously difficult drug to use, it is marketed by Bristol-Myers Squibb under the name Coumadin. Some industry analysts said the efficacy of the product had been considered a given and the questions about its effectiveness amounted to a setback for approval hopes.

Five clinical trials tested Exanta in nearly 18,000 patients and showed it takes effect more quickly and requires less frequent testing than warfarin, AstraZeneca officials have said. Company spokeswoman Rachel Bloom-Baglin said the studies showed a "strong, positive balance of benefit to risk." FDA officials also questioned the drug's possible toxic effects on the liver. The company's risk plan for the product did not address some possible concerns, including risks of delayed liver toxicity after short-term use, heart failure or excessive bleeding caused by Exanta, the reviewers said. Hamish Cameron, AstraZeneca's vice president of cardiovascular, said the company had been open about the liver problem. "We're happy to do more," Cameron said.

Exanta is a pivotal product for AstraZeneca, which needs to make up for declining sales of its ulcer pill Losec/Prilosec, now facing generic competition. The drug is already approved in Europe to prevent blood clotting after orthopedic surgery, but analysts estimate nearly 80% in sales could lie in stroke prevention. Hence the decision to not approve Exanta announced the following day sent shares in AstraZeneca already down by 4% following the FDA review down still further. Despite the Committee members' recognition of the need for a new oral therapy to complement warfarin in the treatment of thrombotic disorders, the Committee advised that the indications for the prevention of strokes in patients with atrial fibrillation (AF), for the prevention of blood clots in patients undergoing knee replacement surgery, and for the long term secondary prevention of blood clots following standard treatment of a clot, should not be recommended on present data.

Sir Tom McKillop, Chief Executive of AstraZeneca, said "We are disappointed with the outcome of the Advisory Committee, particularly for patients who need an effective alternative therapy to warfarin, the only existing oral anticoagulant. We will now continue our discussions with the FDA on a way forward for Exanta." [more on this story]

News from the 40th Annual Meeting of the European Association for the Study of Diabetes (EASD)

According to WHO, there are some 130 million diagnosed diabetics in the world, a figure that is predicted to increase to 300 million by 2025. The majority of patients suffer from type 2 diabetes however type 1 diabetes (also known as insulin-dependent diabetes (IDDM) or juvenile-onset diabetes) is common affecting 10-15% of all diabetes sufferers.

The market for diabetes therapeutics is also rising with global sales reportedly topping $8.1 billion for the 12 months to September 2000, a 19% increase over the previous 12 months (for a full analysis of diabetes therapeutics and market opportunities click here). Oral antidiabetic drugs, the leading class of drugs used to treat the disease, accounted for almost 63% of sales during this period, while sales of insulin stand at around 30%. Further increases are inevitable and the market for diabetes medications could exceed $20 billion by 2006.

Associated with diabetes is the metabolic syndrome, a cluster of three or more metabolic risk factors, including abdominal obesity, low levels of HDL-C, increased levels of triglycerides, raised blood pressure and raised blood glucose. The condition is very common; indeed in a recent report published by the analysts DataMonitor, it was estimated that approximately 115 million individuals suffer from metabolic syndrome in the seven major markets. This patient population is set to grow rapidly in response to the rising obesity and diabetes epidemics (click here for the report).

The EASD held last month in Munich heard data from the COmparative study with rosuvastatin in subjects with METabolic Syndrome (COMETS).

Correcting dyslipidemia in these patients represents a clinical objective for the treatment of metabolic syndrome and will increasingly contribute to the market for anti-dyslipidemics which achieved global sales of $21.7 billion in 2002, a growth rate of 12.5% over 2001. Due to the maturing of the market, evidenced by the increasing availability of generic statins, growth in this market has slowed in recent years however grow is expected to continue as only around 35% of people with high cholesterol are aware of their condition and only 12% are currently treated . Crestor represents one of the newest anti-dyslipidemics to reach the US and EU (click here for an analysis of the statins). First approved in the Netherlands in 2002 CRESTOR has since been approved in more than 60 other countries. FDA approval was gained in 2003. CRESTOR has been successful in penetrating these markets, having achieved around a 30% market share although concerns over safety led to slower initial uptake.

CRESTOR and Pfizer's Lipitor (atorvastatin), the dyslipidemia market leader and the world's largest revenue-generating product with 2002 sales of $8 billion are currently two of the key players in the battle for the dyslipidemia market. The COMETS study which compares the two agents head to head is thus of considerable interest.

This study showed that at the 20mg dosages AstraZeneca's CRESTOR (rosuvastatin) reduced LDL 49% and raised HDL by more than 10%, a statistically significant finding compared to another commonly prescribed statin, atorvastatin, in patients with metabolic syndrome. COMETS is the first international prospective study of statin treatment in people with the metabolic syndrome.

"The rising number of people with the metabolic syndrome has serious implications for public health," said Dr. Christie Ballantyne of Baylor College of Medicine and COMETS study investigator. "Results from this study show that CRESTOR is an effective medication for this 'higher risk' patient group, offering significant benefits by correcting abnormal lipid levels, both lowering bad cholesterol and raising good cholesterol." COMETS is a twelve-week study conducted in 68 centers in seven countries to compare the efficacy and safety of CRESTOR to atorvastatin and placebo. Results showed CRESTOR at 10mg reduced LDL-C by 42% after six weeks compared with 36% for atorvastatin at the same dose. CRESTOR 20mg, at 12 weeks, reduced LDL-C by 49% compared with 43% with atorvastatin 20mg [more]

A second study featured in this edition of PharmaNews Bytes from the EASD underlines the potential benefits of liraglutide, Novo Nordisk's investigational GLP-1 analogue as a novel treatment for type 2 diabetes.

Approximately 60% of diabetes patients do not achieve target A1C levels with their current treatment regimen. According to the ADA, patients with A1Cs above target are more likely to develop diabetes-related complications, such as kidney disease, blindness and heart disease. This evidence of suboptimal diabetes therapeutics has prompted the drug development sector to develop new and improved therapeutic options.

Oral antidiabetic drugs, the leading class of drugs used to treat diabetes, were up until recently synonymous with focused on metformin and sulphonylurea. The explosion of drugs available for controlling blood glucose began when Glucophage (metformin) became available in 1995, quickly followed by the approval of the insulinotropic agent Repaglinide in 1997 and the thiazolidinedione insulin sensitizers such as Avandia and Actos, which were both launched in 1999.

GLP-1 has attracted attention of researchers as a new approach to treat diabetes. GLP-1 is a gut hormone, also known as incretin, released after food consumption to stimulate insulin secretion and mimics of this hormone or molecules that prevent its breakdown are of considerable therapeutic potential as anti-diabetic drugs. Although GLP-1 demonstrates a number of potential benefits for type 2 diabetes, in its natural state it is rapidly broken down and is not practical as a therapeutic agent. Liraglutide is a once-daily long-acting analogue of this naturally occurring hormone and has already completed phase 2 clinical trials. Novo Nordisk expects to initiate phase 3 clinical trials by the end of 2004.

The study presented at the EASD showed that liraglutide, used alone or in combination with metformin, improves glycemic control (fasting serum glucose) compared to using metformin alone. In combination with metformin, liraglutide improved both glycaemic control (fasting serum glucose and HbA1c) and weight control when compared to glimepiride with metformin.

In the randomised, double-blind clinical study of 144 subjects with type 2 diabetes, liraglutide when used alone, resulted in a significant reduction in fasting serum glucose. In combination with metformin, liraglutide demonstrated improved glycemic and weight control compared with glimepiride and had a considerably greater impact on HbA1c than either agents administered as a monotherapy. These new findings add to the growing body of data supporting the potential of liraglutide as a promising and valuable therapy for treating type 2 diabetes, said Professor Michael Nauck, Diabeteszentrum, Bad Lauterberg, Germany, who presented these latest clinical data on liraglutide. He explained that the treatment of type 2 diabetes is complicated by the need to treat frequent co-morbid conditions such as obesity, but that none of the currently available medications result in weight loss [more on this story]

New data announced on Sept 7th showed that the oral insulin formulation, EXUBERA was effective and well tolerated in controlling blood glucose levels over a two-year period in patients with Type 2 diabetes.

The largest unmet need in the diabetes market is improved delivery of insulin. Currently, the predominant mode of insulin administration is subcutaneous injection, which is extremely unpopular among patients. This, in part, explains why only 13-28% of drug-treated type 2 diabetes patients receive insulin therapy. Analysts believe however that there will be a shift towards earlier initiation of insulin in the future, along with increased uptake, following the introduction of non-injected insulin (for an in depth analysis click here). Consequently much effort is being placed on identifying new insulin delivery technologies, with inhaled and oral formulations both representing strategies under development. Most experience with inhaled insulin has been obtained using Exubera. Although phase III studies were completed in July 2001, further studies were initiated due to changes in FDA guidelines governing inhaled therapeutics. Following the report of this potential delay in regulatory filing, analysts predicted that launch would take place between 2002 and 2003, generating peak sales of anywhere between $250 million and $1.25 billion by 2006. Launch has yet to take place. In February 2004, Pfizer and Aventis submitted EXUBERA for review by the European Medicines Agency for marketing approval in the European Union. Interactions with the European regulatory authorities are ongoing.

The results, presented at the EASD, were combined results from two six-month clinical studies in patients with type 2 diabetes that were designed to assess the efficacy of EXUBERA when added to either sulfonylurea or metformin as compared to the combination of these oral agents without EXUBERA. Following the initial six-month trials, patients continued into extensions of up to an additional 18 months, where the primary objective was to assess long-term pulmonary safety. A total of 304 patients completed the two-year period.

During the two year period, patients in both the EXUBERA and the control treatment groups experienced declines in pulmonary function from baseline measured as FEV1and DLCO (carbon monoxide diffusing capacity). At week 24, small differences in declines in FEV1 and DLCO in favor of oral agents were observed. After two years of treatment, though, no significant differences between treatment groups were found. In addition, study results showed that HbA1c, an indirect way to measure blood glucose levels over time, decreased from 9.6% to 7.7% after two years for patients receiving EXUBERA and to 8.1% for patients in the control group. The most common adverse event in the Exubera-treated group was cough, which was considered to be transient and mild.

"These data show that small pulmonary function differences between the two groups occurred early after treatment initiation, had no identified clinical relevance, and did not progress with two years of continued inhaled insulin treatment," said Professor Manfred Dreyer, lead study investigator, Bethanien Krankenhaus, Hamburg, Germany [more on this story]

A second release on the same day announced results from Generex's pharmacodynamics and pharmacokinetics study of its oral insulin treatment, Oralin.

The purpose of the study was to compare Oralin, a buccal spray insulin formulation, with sub-cutaneous administration of insulin in healthy subjects. In this randomized crossover study, seven healthy volunteers received four different doses of buccal spray and a single dose of s.c. insulin under euglycemic clamp. Oralin had an earlier onset of action, more rapidly produced peak plasma insulin concentrations and had a shorter duration of action. The maximum insulin levels were comparable in the s.c. vs the highest dose of Oralin. In a second study presented at the EASD, Oralin was compared to s.c. regular insulin and to placebo spray in patients with type 1 diabetes. As in control subjects, Oralin had a faster onset and a shorter duration of action compared to s.c. regular insulin. It is mainly absorbed and effective in the first two hours after administration and therefore Oralin is well suited for the management of postprandial glucose excursions in type I diabetics [more on this story]

Long-awaited FDA decisions on pain therapeutics

Approximately 9% of the US population suffers from moderate to severe non-cancer-related pain, a figure that includes 40-70 million individuals with chronic pain. This condition precipitates other serious pathologies such as depression and is associated with an estimated pharmaceuticals market of US$18.7 billion worldwide. Since chronic pain is notoriously difficult to treat using currently available therapeutics, the development of analgesics has represented a major pharmaceutical objective.

The origins of pain range from nociceptive (caused by tissue injury or inflammation) to neuropathic. Approximately 26 million patients worldwide (10 million in the US) suffer from some form of neuropathic pain, spending an estimated $2-3 billion annually on treatments.

Neuropathic pain represents a problem associated with a wide variety of conditions including trauma, HIV infection, shingles, diabetes, immune disorders, and toxic neuropathies (for example following treatment with chemotherapeutics). The drug development community is starting to approach the various sub-types of neuropathic pain as separate etiologies in order to facilitate entry into this massive market and also in an attempt to improve therapeutic efficacy (Editor's note: LeadDiscovery has a portfolio of specialist reports evaluating opportunities surrounding the sub-types of neuropathic pain - click here for a full listing).

In the absence of specific treatments of neuropathic pain this market has been led by Pfizer's gabapentin (Neurontin). Gabapentin was originally approved by the FDA as an anti-convulsant for use in the treatment of epilepsy, and in 2003 it led the global anti-convulsant market with global sales across all indications of over $2.7 billion. This represented 19% growth compared to 2002 sales. It is however estimated that a significant proportion of gabapentin's sales are for neuropathic pain indications despite never receiving official approval for this indication in the US apart from postherpetic neuralgia. Diabetic neuropathic pain, a key symptom of diabetic neuropathy caused by chronic glycemia affects over 3.7 million patients in the US alone and represents one of the major off-label uses of gabapentin (for further information on emerging treatments of diabetic neuropathic pain click here). This situation is about to change as result of two key events.

Firstly, Ivax received final approval of its abbreviated new drug application for gabapentin tablets from the FDA in April, 2004. Pfizer has attempted to prevent IVAX from selling gabapentin however legal appeals were blocked by US courts and IVAX went to market earlier this month. Secondly, in July, 2004, Pfizer won EU approval to market the follow-up to gabapentin, pregabalin (Lyrica) for the treatment of peripheral neuropathic pain and as an adjunctive therapy for partial seizures in patients with epilepsy. This drug is currently undergoing review by the FDA for the management of neuropathic pain associated with diabetic neuropathy and postherpetic neuralgia, as adjunctive therapy for partial seizures, and for the treatment of generalized anxiety disorder.

Like gabapentin, pregabalin, a 3-substituted analogue of gamma-amino butyric acid (GABA) binds to calcium channels and modulates calcium influx as well as influencing GABergic neurotransmission. This mode of action translates into anti-epileptic, analgesic and anxiolytic effects. Because it is more potent than gabapentin, pregabalin achieves efficacy at lower doses. This increases its therapeutic index with respect to gabapentin and should lead to fewer dose-related side effects.

Pregabalin has long been under review by the FDA for the management of neuropathic pain associated with diabetic neuropathic pain, shingles, as adjunctive therapy in the treatment of partial seizures, and for the treatment of generalized anxiety disorder in adults. Although Pregabalin has been approved in the EU, safety concerns have severly delayed the FDA decision.

On Sept 2 however, Pfizer announced that US regulators had approved pregabalin if certain conditions are met.

Pfizer said the FDA had issued "approvable letters" indicating the drug, Lyrica, could be approved for partial seizures in adults, neuropathic pain caused by diabetes and pain following herpes infections, if the agency's conditions are met. The FDA however issued a "non-approvable letter" for use of the drug to treat generalized anxiety disorder, which makes approval for that indication less likely in the foreseeable future (for an analysis of anxiety therapeutics click here).

A company spokesman said he was not able to specify the FDA's conditions for approval or other details involving the agency review of pregabalin which Wall Street expects to become a blockbuster treatment if it wins final approval. "This is certainly not positive," said David Moskowitz, an analyst for Friedman, Billings, Ramsey, who added that his 2004 pregabalin revenue projection of $130 million was now at risk. "The fact that they got a non-approvable letter for generalized anxiety disorder is a negative since Lyrica was expected to get approved for all the off-label indications that Neurontin is being used for," Moskowitz said. SG Cowen analyst Steve Scala had estimated Lyrica would generate sales of $500 million in 2005, growing to $2 billion by 2008. But those numbers may now be revised downward. Other analysts including Sena Lund, at Cathay Financial were more upbeat commenting "At least it shows Pfizer is on track to get pregabalin out of the FDA and get it to market". Investors did not seem overly concerned by the apparent setback, moving Pfizer shares 1% higher on Thursday. Pfizer closed up 35 cents at $32.70 on the New York Stock Exchange. [More on this story]

A few days later on Sept. 7 Lilly announced that FDA has approved their neuropathic pain treatment, the antidepressant Cymbalta (duloxetine), judging it safe and effective for the management of diabetic peripheral neuropathic pain.

This announcement means that Lilly has beaten Pfizer to the post, with Cymbalta becoming the first FDA-approved treatment for pain caused by diabetic peripheral neuropathy. This approval came after a six-month priority review. This is the second time in a month that the FDA has judged Cymbalta, a balanced and potent serotonin and norepinephrine reuptake inhibitor, a safe and effective therapy for a major medical disorder. On Aug. 3, the agency approved Cymbalta as a treatment for major depression in adults (click here for an analysis of the antidepressant market). With the global antidepressant market valued at $16.6 billion in 2002, drugs for the treatment of depression have historically provided huge returns on investment. Several of the leading brands are expecting patent expiries over the next five years and the approval of Cymbalta for this indication means a predicted revenue of $2.1 billion by 2011. It's available immediately by prescription in pharmacies across the United States for the treatment of major depression or pain associated with diabetic peripheral neuropathy.

Lilly proved Cymbalta's safety and efficacy in the treatment of pain caused by diabetic peripheral neuropathy at doses of 60 and 120 mg per day in two randomized, 12-week, double-blind, placebo-controlled, fixed-dose studies in non-depressed adults who had the disorder for at least 6 months. Although both doses were safe and effective, 120 mg was not as well tolerated as 60 mg per day. In both studies, Cymbalta significantly reduced 24-hour average pain, compared with placebo. Improvements were noted as early as the first week of treatment and continued for the duration of the studies. In addition, Cymbalta showed rapid onset of action and sustained effect in reducing pain caused by diabetic neuropathy at both 60 mg per day and 120 mg per day, and was effective in relieving pain at night. Nighttime pain is especially troublesome to many patients with diabetic neuropathy, because it can interfere with sleep. [More on this story].


Last updated on: 27/08/2010 11:40:18

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