GlaxoSmithKline: progress for Rotarix in key US market
15 Aug 2007
GlaxoSmithKline’s rotavirus vaccine has been accepted for review by the FDA.
The FDA has accepted GSK’s application for Rotarix for review. Rotarix, a live attenuated vaccine derived from the most common human rotavirus strain, is used in infants to prevent rotavirus gastroenteritis. Rotavirus infects nearly every child worldwide by age five and is the leading cause of severe acute gastroenteritis in infants and young children.
The first rotavirus vaccine to be launched was Wyeth’s RotaShield in 1998, but the product was withdrawn from the US following its association with intussusception (an in-folding of the bowel). Subsequently, the FDA approved Rotarix’s main competitor in February 2006: Merck’s live, oral vaccine RotaTeq.
RotaTeq contains five live human-bovine reassortant serotypes (G1, G2, G3, G4, and P1), which account for at least 75% of rotavirus strains worldwide. RotaTeq is administered in a three-dose regimen beginning at the age of two months. GSK’s Rotarix, meanwhile, was first launched in Mexico in January 2005 and received EU approval in February 2006. Rotarix shows efficacy against the rotavirus serotypes G1, G2, G3, G4 and G9 and is administered in a two-dose regimen given at an age of six to 24 weeks.
Although both vaccines are highly effective in preventing rotavirus infection, their high price of approximately $200 for the full regimen has restricted integration into national immunization schedules. The US is the only major market that has recommended rotavirus vaccination for all infants, making it a crucial commercial opportunity for both RotaTeq and Rotarix.
Although RotaTeq, which has been available in the US for over a year, enjoys the first-to-market advantage, Rotarix has the potential to become a significant competitor upon US approval. While both drugs demonstrate good efficacy and safety, Rotarix’s more convenient dosing scheme and broader subtype coverage give it an edge over Merck’s product.
However, in the highly price-sensitive vaccines market, launching Rotarix at a lower price than RotaTeq would be the most promising approach to encourage physicians to switch from the established brand to a new product, and to guarantee rapid uptake in the US.
Wyeth: yet more bad news for Pristiq
10 Aug 2007
Wyeth has terminated the development of Pristiq for the treatment of fibromyalgia.
The termination of Pristiq for fibromyalgia represents another setback for Wyeth, which had high hopes for its follow-on drug to Effexor. However, all is not lost as Wyeth’s greatest commercial opportunity for Pristiq will be gained through indications for depression and menopausal symptoms, although heart and liver safety concerns added to regulatory delays may still limit the drug’s potential.
The development of Pristiq (desvenlafaxine succinate) for fibromyalgia was terminated during the enrollment of participants in a Phase III clinical trial after Wyeth reviewed a planned interim data analysis and concluded that Pristiq would not outperform a placebo in reducing pain. Pristiq is a metabolite of Wyeth’s successful antidepressant, Effexor (venlafaxine), and like Effexor, is a serotonin-norepinephrine reuptake inhibitor (SNRI).
Coupling a large patient population with high unmet medical need, fibromyalgia is one of the most keenly anticipated new CNS drug markets, with Pfizer’s Lyrica (pregabalin) becoming the first drug to receive approval from the FDA for the disease in June 2007. Close behind is Eli Lilly’s Cymbalta (duloxetine), which is also a SNRI.
However, unlike Pristiq, clinical trials have shown Cymbalta can provide significant pain relief for fibromyalgia patients. Datamonitor forecasts that the FDA will approve Cymbalta by 2008 and the drug will generate peak sales in this indication of $579 million in 2012.
The predicted success of Cymbalta in fibromyalgia hints at what Wyeth will now miss out on. Nevertheless, the company has not put all its eggs in one basket. Pristiq is in pre-registration for its primary focus markets of depression and vasomotor symptoms of menopause, although developments for these indications are not without drawbacks.
As part of its application for menopausal symptoms, the FDA has recently asked Wyeth to submit more data over concerns of potential liver and heart affects. The request stalls Wyeth’s plans to market Pristiq as the first non-hormonal drug for hot flushes and other menopause symptoms by at least a year and casts further doubt over its potential in this market.
Although Wyeth claims these safety concerns are unlikely to impact on the drug’s application for depression, it will hurt an already unconvincing lifecycle management strategy. Pristiq is not expected to maintain revenues of Wyeth’s depression franchise following generic incursion of Effexor XR in 2010 and is forecast to generate depression specific sales of $644 million by 2016 in the seven major markets.
Bristol-Myers Squibb: Orencia is rejected by NICE in the UK
03 Aug 2007
The NHS’ cost watchdog has rejected Bristol-Myers Squibb’s Orencia for rheumatoid arthritis.
The initial recommendation from the National Institute for Health and Clinical Excellence (NICE), which was made over grounds of Orencia (abatacept) not being cost-effective, is only a preliminary judgment and the final decision to fund the therapy will be discussed at the second appraisal committee meeting in September 2007. Orencia, produced and marketed by Bristol-Myers Squibb, is a T cell co-stimulation modulator that targets CD28 preventing the interaction with CD80/86 on antigen presenting cells. Orencia, which is the first in its class, is administered by intravenous infusion over 30 minutes.
Launched in the US market in Q1 2006, Orencia is aimed at refractory rheumatoid arthritis (RA) patients who have failed anti-TNF treatment and have responded inadequately to methotrexate. BMS submitted an application for Orencia in the EU in January 2006. After EU approval in May 2007, BMS launched Orencia in the UK in June 2007, where it is licensed for use in combination with methotrexate for the treatment of moderate-to-severe RA patients who have not responded to disease modifying drugs, including at least one anti-TNF, for example Wyeth’s Enbrel (etanercept), which is currently the UK market leader.
NICE has investigated the effectiveness of Orencia based on data from six randomized controlled clinical trials, many of which were conducted in patients who failed anti-TNF therapy. Overall, NICE concluded that Orencia was not cost-effective because it would cost over GBP30,000 per quality adjusted life year (QALY) gained.
Datamonitor estimates that the UK is the third largest RA population, behind the US and Germany, and has close to 500,000 patients. Therefore, the draft decision by NICE not to fund Orencia will come as a blow to both BMS and to RA patients. However, it is not over for Orencia in the UK as the appraisal committee will review their decision in September 2007.
The Scottish Medicines Consortium, Scotland’s equivalent of NICE, will announce their decision concerning Orencia on September 10, 2007.The outcome of this decision may be a predictive factor of NICE’s future decision. And despite this initial obstacle, Datamonitor believes that Orencia will achieve sales of around $1.2 billion in the seven major markets by 2016.
Eli Lilly: closer to expanding Evista brand
31 Jul 2007
An FDA panel has voted in favor of extending the approved indications for Eli Lilly’s Evista.
Lilly sought approval for the breast cancer risk reduction indication for Evista, currently marketed for osteoporosis, following the results of the STAR trial, which have now been published extensively. Initial findings indicated that in 19,747 women randomized to 60mg of Evista (raloxifene) or 20mg of tamoxifen over four years, raloxifene was as effective as tamoxifen for preventing breast cancer in high-risk women.
However, later analyses revealed that more cases of lobular and ductal carcinoma arose in women treated with Evista than with tamoxifen. Additionally, women with intact uteri and those sexually active while receiving raloxifene were more likely to suffer dose-limiting side effects than those receiving tamoxifen.
The RUTH trial also indicated an increase in the risk of stroke mortality while taking raloxifene.While researchers have downplayed these findings, the American Cancer Society, patient advocacy groups and some FDA panelists have voiced their concern.
In 2006, Evista returned $739 million for Eli Lilly as a key product in its women’s health franchise. The company operates a careful lifecycle management strategy of Evista, marketing the brand alongside another key product, Forteo (teriparatide), also indicated for the treatment of osteoporosis. With the 2012 patent expiry of raloxifene in the US impending, events in the lifecycle of both brands, including the acquisition of the breast cancer risk reduction indication, have been strategically timed in collaboration with each other to optimize the osteoporosis market revenue stream.
The menace of safety fears and the imminent launch of Wyeth’s rival selective estrogen receptor modulator bazedoxifene, which is forecast to generate brand sales of $601 million in 2016, have been worrying for Lilly. Consequently, the decision reached by the advisory panel should come as a relief to the company. Approval of the additional indication, which looks likely, would strengthen Lilly’s position in the women’s health market, and is expected to boost the company’s revenue from the osteoporosis market, to reach $1.12 billion in 2016.
MedImmune: FluMist recommendation represents crucial milestone
17 May 2007
An FDA advisory committee has recommended MedImmune’s FluMist in children aged one to five.
According to the FDA Vaccines and Related Biological Products Advisory Committee (VRBPAC), clinical data supported efficacy of the vaccine in healthy children aged 12 to 59 months. Despite earlier safety concerns about the use of FluMist in children with a history of wheezing, VRBPAC voted in favor of the risk-benefit profile of FluMist in children 24 to 59 months of age regardless of a history of wheeze. Following the meeting, the FDA is expected to officially approve FluMist in children aged one to five years by its Prescription Drug User Fee Act date on May 28, 2007.
This expansion of FluMist’s target population is a crucial milestone for the Gaithersburg, Maryland-based company. Ever since its original approval in 2003 as the first and only inhaled influenza vaccine, FluMist’s commercial uptake has been hampered by the approved age range: the 5-49 year olds constitute the least attractive target group. Influenza high-risk groups such as young children and the elderly have been excluded.
Disappointing sales in the first influenza season after launch (2003/2004) caused Wyeth, the original marketing partner, to terminate the agreement in 2004. FluMist’s revenues have barely moved since: MedImmune reported sales of $21 million and $36 million in 2005 and 2006, respectively. During the past flu season, FluMist had a market share of 2.5% by volume in the US.
Due to its high efficacy and its convenient, needle-free mode of administration, MedImmune expected FluMist to be particularly suitable for childhood vaccination and has been conducting numerous studies to prove the vaccine’s efficacy and safety in young children in order to gain access to this patient group and multiply FluMist revenues. Indeed, yesterday’s FDA recommendation is timely: following its $15.6 billion acquisition of MedImmune in April 2007, AstraZeneca indicated plans to conduct “one final push” in marketing FluMist and to potentially offload the flu vaccine business in case of another failure.
Astellas Pharma: telavancin enters EU battle for MRSA market share
02 May 2007
Astellas has submitted a Marketing Authorization Application to the EU for antibacterial telavancin.
Following the US NDA filing of telavancin in February 2007, Astellas has now followed up with a European application. Its latest treatment for serious bacterial infections should strengthen its portfolio of products targeting the hospital market. Akin to many late stage pipeline products currently in development, trial design objectives have been explicitly oriented towards the management of methicillin-resistant Staphylococcus aureus (MRSA).
MRSA has become one of the most common causes of nosocomial infections worldwide. One study demonstrated that some 50% of infectious morbidity in intensive care units were partially due to MRSA. More recently, it has been acknowledged that the pathogen is increasingly being isolated in community-acquired infections, and has been associated with life-threatening conditions including necrotizing pneumonia and necrotizing fasciitis.
There are products on the market for MRSA already.Vancomycin remains a drug of choice, but the risks associated with treatment failure and rising rates of vancomycin resistance have led to clinicians reverting to older drugs, such as co-trimoxazole, clindamycin, minocycline, fluoroquinolones and doxicycline, none of which provide a comprehensive solution to MRSA management.
There are also newer competitors already on the market. If approved, telavancin will enter the market behind a number of key competitors: Pfizer’s Zyvox, (linezolid) first launched in the EU in 2001 (and is already exhibiting resistance, but available orally), Cubist and Novartis’ Cubicin (daptomycin, shows limited tissue penetration and requires patient monitoring but dosed once daily) and Wyeth’s Tygacil (tigecycline, good empiric activity apart from Pseudomonas aeruginosa) in 2006 and Pfizer’s Zeven (dalbavancin, available once weekly, but with limited patent coverage left) is likely to launch months before Telavancin.
Nevertheless, if it is approved within expected timelines, telavancin will beat several other key competitors to the EU market, namely Johnson & Johnson’s in-licensed compounds ceftobiprole and doripenem (originating at Basilea and Shionogi, respectively), Advanced Life Sciences’ cethromycin and Arpida’s iclaprim. This offers Astellas crucial time in which to establish its core message:Telavancin is a valuable weapon against MRSA that can be administered at dosing levels that enable rapid bactericidal activity and has a predictable pharmacokinetic profile, making it an effective and safe choice.
Wyeth: optimizing bazedoxifene’s lifecycle strategy
25 Apr 2007
The FDA has granted conditional approval to Wyeth’s bazedoxifene molecule.
Conditions for approval include an appraisal of Wyeth’s manufacturing and testing facilities for the drug and a final examination of safety and efficacy data from pivotal clinical trials.The company has already indicated that the approvable letter places bazedoxifene on track for launch, which Datamonitor predicts to be in Q3 of 2007.
However, the uptake of Viviant with a prevention indication alone will be fairly limited. Wyeth intends to maximize patient potential with the launch of a reformulation combining bazedoxifene with Premarin, a conjugated equine estrogen. The combined therapy, Aprela, should be effective in treating osteoporosis while reducing menopausal symptoms. This would open up bazedoxifene/Premarin therapy to the whole postmenopausal market by providing a continuum of care throughout the menopausal period.
The third step of the strategy will see bazedoxifene sales receiving a further boost if it is approved as a treatment of postmenopausal osteoporosis, which is predicted to come in Q1 2009, around three months after the expected launch of the reformulation.
These strategies, coupled with the fact that bazedoxifene will be only the second selective estrogen receptor modulator (SERM) to market, have led Datamonitor to forecast that by 2010 total sales generated by the bazedoxifene brand will reach $557 million in the seven major markets. Forecast sales climb to $601 million in 2016, making it the third highest selling brand in the osteoporosis market at this time.
Denosumab (Amgen, phase III) and Aclasta (Novartis, preregistration) are expected to lead the market in 2016, generating blockbuster revenues.Their success will be driven by favorable intermittent dosing, which is something bazedoxifene does not benefit from. Other challenges to bazedoxifene in the osteoporosis market include the potential gain, by class competitor Evista, (raloxifene, Eli Lilly), of a label for breast cancer risk reduction and eventually the entry of generic SERMs as Evista loses patent in 2012. In spite of these and other challenges, the lifecycle strategy adopted by Wyeth is expected optimize bazedoxifene’s potential in the osteoporosis market.
Antibacterials: narrow-spectrum strategy could change market
28 Mar 2007
Narrow spectrum antibiotics found to reduce Clostridium difficile infections in hospitals.
A new study published in the Journal of Antimicrobial Chemotherapy illustrates a correlation between the use of broad spectrum antibiotics and increasing rates of Clostridium difficile infections. The research demonstrates that equipping doctors with a pocket sized laminated card listing antibiotic usage guidance, implementing a narrow spectrum policy across the hospital and utilizing feedback on antibiotics use and CDI rates, led to a significant drop in prescriptions of broad spectrum antibiotics and an accompanying decline in C. difficile infections.
C. difficile is a gram-positive anaerobic, spore-forming bacillus and the most commonly recognized cause of antimicrobial drug-associated diarrhea. C. difficile infections are becoming increasingly common among patients of long-term care facilities and even within the community environment. However, it mainly affects patients in short-stay hospitals, where epidemic strains of C. difficile may be transmitted extensively both within and between facilities. These infections are associated with substantially increased healthcare costs and prolonged hospital-stay.
Antimicrobial exposure is the greatest risk factor for patients, especially broad spectrum agents such as clindamycin, cephalosporins and penicillins. Antibiotic therapy alters the levels of beneficial bacteria in the colon, consequently facilitating colonization by C. difficile if it is present in the environment. Cases of infection un-associated with prior antimicrobial usage are rare.
Recently there has been a notable rise in C. difficile infections associated with a more virulent strain. The majority of these cases have been across North America, although outbreaks of this strain have also been reported in the UK.
Despite the study’s finding that most C. difficile cases would be preventable through disciplined use of narrow spectrum agents, to replicate such success across the hospital sector would require improved diagnostic methods and the availability of effective narrow spectrum agents.
This would offer further potential benefits resulting from the reduced selective pressure for multi-drug resistant bacteria. Since the majority of more recently introduced hospital antibacterials are broad spectrum agents – such as Wyeth’s Tigecycline and Cubist/Novartis’ Daptomycin – a widespread adoption of narrow spectrum policies, similar to the Royal Free’s, could have a substantial negative effect on hospital antibacterial market sales through a reduction in the market opportunity for broad spectrum antibacterials.
MRSA: superbug expected to drive growth of niche market
20 Dec 2006
First cases of multi-drug resistant superbug CA-MRSA have been reported in a UK hospital setting.
UK newspaper The Times recently reported the death of a healthy young hospital worker who had contracted a new, particularly virulent Panton-Valentine Leukocidin positive strain of methicillin-resistant Staphylococcus aureus (MRSA). According to the Health Protection Agency, this case is the most recent in a series of eight cases of infection with this usually community-associated (CA) MRSA strain in a West-Midlands hospital.
However, these fatalities are not isolated cases, but just the most recent development in a long history of MRSA in the UK. First discovered in 1961, the multi-resistant superbug has emerged to become a public health concern in the following decades. The percentage of MRSA in death certificates mentioning S. aureus has risen from 12% in 1993 to 66% in 2002, and by 2004/05, MRSA accounted for 44% of all S. aureus bacteremia cases, this being the highest share throughout all EU countries.
The spread of a CA-MRSA strain into the hospital setting, as observed in the West Midlands, has occurred before, particularly in the US. Indeed, the US tends to be a good indicator for future infection trends with regards to MRSA.
As a result of the overall rising incidence of MRSA, the market for antibiotics for this indication is experiencing a significant growth and has become highly attractive for pharma companies. Pfizer’s Zyvox (linezolid) has become the second most popular treatment option after vancomycin and reported global sales of $609 million in 2005, according to IMS Health. Wyeth’s Tygacil (tigecycline) and Cubist’s Cubicin (daptomycin) are establishing themselves as alternative regimens.
With several other candidates such as Theravance’s Telavancin or Pfizer’s Zeven (dalbavancin) in late stage development, Datamonitor predicts that MRSA drugs will achieve sales exceeding $200 million in 2010 in the UK alone, growing at 41% CAGR from 2005. However, especially in the light of the increasing CA-MRSA incidence, oral MRSA drugs remain a key unmet need that has not been addressed by any drug developer yet, indicating that there is still room in the dense market.
Solvay, Wyeth and Lundbeck: high expectations for schizophrenia drug
07 Dec 2006
Clinical data demonstrates that bifeprunox improved stability in patients with schizophrenia
In a six-month, placebo-controlled, phase III study involving patients with stable schizophrenia, Solvay, Wyeth and Lundbeck’s investigational drug bifeprunox demonstrated superiority over placebo in preventing deterioration of symptoms. In another study, bifeprunox improved symptoms in patients with acute exacerbations of schizophrenia, although a smaller mean effect was demonstrated than for active references versus placebo. The most common side effects reported with bifeprunox in these studies were gastrointestinal in nature. In October 2006, Solvay and Wyeth filed an application to the FDA for the use of bifeprunox in schizophrenia.
Schizophrenia is a chronic form of psychosis characterized by profound disruption in cognition and emotion. Symptoms are typically divided into positive and negative symptoms and include hallucinations, delusions, poverty of speech, disorganized thought and emotional blunting. Schizophrenia has a prevalence rate of approximately 1.1% in the US population.
A key unmet need in the treatment of schizophrenia is improving patient compliance. According to opinion leaders interviewed by Datamonitor for its recently published schizophrenia pipeline insight report, many patients stop taking their medication for extended periods of time, primarily due to drug side effects; which seriously compromises their treatment. These side effects include weight gain and metabolic disturbances such as glucose and triglyceride elevations. In the recently completed clinical studies, a positive therapeutic profile was reported, with bifeprunox conferring a favorable weight and metabolic profile versus placebo or active references.
In view of the fact that the side effect profile of atypical antipsychotics remains a highly problematic feature of their drug profile, Datamonitor believes that the favorable weight and metabolic profile of bifeprunox will lead to improved patient compliance. Given that prospective players in this market will face stiff competition from both established brands and cheaper generics, the side-effect profile of bifeprunox will serve as a key factor differentiating it from other atypical antipsychotics.
Solvay/Wyeth/Lundbeck’s combined psychiatry marketing experience, in conjunction with Lundbeck’s marketing of Serdolect in Europe bodes well for future development and commercial success of bifeprunox, which is expected to be launched in 2008 in the US.