Lecture utile en complÃ©ment de l’article du Figaro du 19 fÃ©vrier, ce long article du Wall Street Journal du 22 fÃ©vrier expose l’histoire de la « guerre » Lucentis vs. Avastin, repris sur HealthDecisions.org ou sur le blog de I. Arons.
Cet article revient notamment sur :
Over the recommended two-year course of monthly injections into the eye, the bill for Lucentis reaches nearly $50,000. While Medicare covers 80% of the treatment cost for the elderly, some patients must pay the rest themselves.
Officials at the center, which administers Medicare, project that Lucentis could over time cost taxpayers more than $1 billion a year and possibly as much as $3 billion annually.
The Lucentis-Avastin showdown has thrown the pharmaceutical world into a tizzy. Genentech, fearful that a potential billion-dollar-a-year product could be headed down the tubes, is urging doctors to stick to Lucentis and its proven efficacy in treating age-related macular degeneration. Doctors are weighing benefit and cost — and often choosing to roll the dice with Avastin, although it is approved only as a cancer treatment, to ensure that less well-off patients get treatment.
Now the federal government is hoping to settle the dispute by funding a head-to-head comparison of the two biotechnology drugs, the first such trial by the National Institutes of Health. If Avastin works as well as Lucentis, the government’s Medicare program for the elderly could save $1 billion or more a year, officials say.
For Genentech, the world’s second-largest biotechnology company by revenue after Amgen Inc., the stakes are high. Lucentis was a surprise hit after its June 30 launch, logging $10 million in sales on its first day and $371 million in the second half of 2006. Eric Schmidt, an analyst at Cowen & Co., estimates the figure could reach $900 million this year and rise to $1.3 billion by 2011.
« This isn’t Avastin Jr., » insists Dr. Semba, the Lucentis development leader.
Genentech, in justifying the cost of Lucentis, says its trials of the drug included more than 6,000 patients who received vision tests, retinal scans and monthly doctor checkups. It was « one of the more expensive clinical trials we’ve run, » says Ronald Park, team leader for pricing. He notes that older drugs for AMD cost nearly $1,000 a dose without improving vision. Lucentis « is a breakthrough drug for a very bad disease, » says Dr. Park.
Joining Genentech in 1989, Dr. Ferrara and colleagues reported they had isolated the vessel stimulant VEGF, or vascular endothelial growth factor. Later they sequenced the gene for VEGF and worked on protein molecules called monoclonal antibodies that block it. That led to Avastin.
In addition to the monkey studies that suggested Avastin molecules couldn’t reach the retina, there were other reasons Genentech didn’t push the drug hard as an eye treatment. Avastin was designed for cancer patients who need the drug to stick around in their bodies to do its work. Although that could raise the risk of cardiovascular problems associated with Avastin, it was worth it for cancer patients facing a terminal disease.
For elderly people with eye disease, Genentech wanted a drug that would home in on the retina, do its work and quickly get eliminated from the body. The drug it found, Lucentis, binds 20 times better to VEGF in retinal cells and is safer, Dr. Ferrara says.
In July 2005, Genentech reported the results of a big Phase III study of Lucentis before a hushed crowd of 2,000 at a medical meeting in Montreal. The studies showed it halted blindness in 90% of people with AMD and improved vision in 30%.[…] The only problem: Approval would take another year.
Then came an apparent solution: At the same meeting, Philip Rosenfeld, a professor at the Bascom Palmer Eye Institute of the University of Miami Medical School, presented a case of a patient who had been going blind and was injected with Avastin. The patient’s retinal scans dramatically improved a week after treatment and vision began to regain sharpness over six months. […] Rather than wait until Lucentis was approved by the FDA, many doctors grasped at the next best thing. With the help of compounding pharmacists who siphoned tiny doses of Avastin into small syringes, eye doctors tried it in thousands of patients. In large doses for cancer, Avastin costs $55,000 a year. The dose used in the eye costs just $20 to $100.
But some specialists say the two drugs, despite their differences, might be equally effective. Dr. Avery, who has a research appointment at the University of California, Santa Barbara, decided in 2005 to do the kind of study Genentech had long ago lost interest in performing. He and Israeli colleague Anat Loewenstein injected Avastin into rabbits’ eyes. The conclusion, says Dr. Avery: « Hey, this does get through the retina. » They published the findings in the journal Retina in February 2006.
Moreover, in a safety challenge to Genentech, Dr. Fung in San Francisco teamed up with Dr. Rosenfeld in Miami, devising an Internet survey to seek swift reports of serious side effects from Avastin.
In a snapshot of more than 5,200 eye patients on Avastin, their survey found four strokes including one death in a person with risk factors, an unsurprising rate for older people, the doctors reported in the British Journal of Ophthalmology in November 2006.
Lucentis itself may raise stroke risk. In late January, Genentech sent out a « Dear Doctor » letter noting that patients taking the recommended dose of Lucentis had a higher rate of strokes (1.2%) than patients taking a smaller dose (0.3%).
With billions of dollars at stake and medical questions unanswered, the National Eye Institute plans to start a two-year trial in May or June to compare safety and efficacy of Avastin versus Lucentis. While the NIH has previously run tests comparing newer brand-name drugs against older and cheaper generics, this is the first time it is pitting two brand-name biotech drugs against each other, says Dr. Ferris, the eye institute’s clinical director. He says the government must conduct the study because it needs to ensure that the widespread use of Avastin is safe.
However, funding for the trial remains uncertain. In part because the government has to purchase all of its Lucentis and Avastin supplies, the eye institute says it can’t afford to fund the trial on its own and is seeking help from Medicare.
Fin janvier, Genentech avait diffusÃ© aux prescripteurs de Lucentis les rÃ©sultats d’une analyse intermÃ©diaire de l’Ã©tude SAILOR, qui montraient une diffÃ©rence statistiquement significative pour l’incidence des accidents vasculaires cÃ©rÃ©braux (AVC) entre un groupe traitÃ© par 0.3 mg et un autre traitÃ© par 0.5 mg (taux d’AVC respectifs de 1.2% et 0.3%), ces taux restant cependant « cohÃ©rents avec les Ã©tudes cliniques pivots, et ne sont pas plus Ã©levÃ©es que le taux d’AVC dans la population gÃ©nÃ©rale d’Ã¢ge et profil similaire ». Par ailleurs, les patients aux antÃ©cÃ©dents d’AVC prÃ©sentaient un risque plus Ã©levÃ© de rÃ©cidive d’AVC.
Dans un courrier datÃ© du 23 fÃ©vrier, Novartis donne les rÃ©sultats d’une nouvelle analyse intermÃ©diaire (donnÃ©es cloturÃ©es au 10 janvier 2007) :
Dans cette nouvelle analyse, le dÃ©sÃ©quilibre concernant l’incidence des AVC entre le groupe recevant Lucentis Ã la dose de 0.5 mg par rapport Ã celui recevant Lucentis Ã la dose de 0.3 mg n’est plus statistiquement significatif. Les taux d’AVC etaient respectivement de 1.3% (13/1217) et de 0.6% (7/1176) pour les patients recevant Lucentis Ã la dose de 0.5 mg et 0.3 mg.
En attendant les rÃ©sultats finaux de cette Ã©tude (deuxiÃ¨me semestre 2007), qui seuls permettront de conclure, il est certainement prudent de vÃ©rifier les antÃ©cÃ©dents d’AVC des patients susceptibles de recevoir Lucentis…
Ceci est le premier billet d’une sÃ©rie sur les outils de veille bibliographique (ou comment surveiller les nouvelle publications).
La procÃ©dure est trÃ¨s simple :
AprÃ¨s avoir choisi sur la page d’accueil un sujet (par exemple… 16. Ophthalmology), il suffit de cocher les journaux dont on veut recevoir la table des matiÃ¨res, puis remplir le formulaire. C’est tout !
Vous retrouverez alors rÃ©guliÃ¨rement dans votre boite email les titres des derniÃ¨res publications, avec un lien direct vers PubMed pour consultter l’abstract. Par ailleurs, les derniers envois sont « archivÃ©s » sur une page internet « personnelle », permettant de choisir et consulter tous les rÃ©sumÃ©s intÃ©ressants en lots.
A noter que l’Ã©diteur d’Amedeo, Bernd Sebastian Kamps, dÃ©fenseur des publications en accÃ¨s gratuit sur internet (nous aurons certainement l’occasion d’en reparler…) est Ã l’origine de nombreux autres services, que je vous trouverez sur sa page d’accueil.
L’expÃ©rience consistait Ã comparer les performances visuelles de deux groupes d’Ã©tudiants, aprÃ¨s un mois de pratique quotidienne soit d’un jeu vidÃ©o d’action (Unreal Tournament 2004), soit de Tetris.
Ainsi, une heure par jour Ã tirer aux quatre coins de lâ€™Ã©cran augmente de 20 % les performances aux tests mesurant la rÃ©solution spatiale. En revanche, Tetris ne modifie en rien les performances visuelles.
Les jeux dâ€™actions entraÃ®neraient le cerveau Ã analyser rapidement des images. Si Tetris exige une bonne vitesse de traitement, les formes Ã reconnaÃ®tre sont graphiquement simples, alors quâ€™un jeu dâ€™action prÃ©sente des scÃ¨nes complexes, au sein desquelles il faut Ãªtre attentif Ã tout.
Le jeu vidÃ©o dâ€™action pourrait-il servir au traitement de lâ€™amblyopie ?