Archives du mot-clé Lucentis

Rythme d’administration du Lucentis

Une publication très intéressante vient de sortir, confirmant l’intuition que certains d’entre nous commençaient à avoir quant au rythme d’administration du Lucentis.

Pour résumer la problématique : dans les études de phase III validant l’efficacité du Lucentis en traitement de la DMLA exsudative (MARINA et ANCHOR), et démontrant une amélioration de l’acuité visuelle, le rythme d’administration était d’une injection intra-oculaire mensuelle, pendant toute la durée de l’étude (1 à 2 ans).
Une troisième étude (PIER), évaluant un rythme différent (traitement d’attaque par 3 injections mensuelles puis traitement « d’entretien » par injections trimestrielles « systématiques »), a montré que si cette modalité permet d’éviter la perte de vision, elle ne permet plus d’observer une amélioration de l’acuité visuelle.
L’alternative testée ici est d’administrer le Lucentis non plus systématiquement (que ce soit tous les mois ou tous les 3 mois) après la période d’attaque de 3 injections, mais sur des critères de variation d’acuité visuelle et d’aspect OCT. Le résultat est une moyenne de 5,6 injections annuelles, et des résultats en terme d’acuité visuelle comparables aux études « pivot » !

Voilà l’abstract :

PURPOSE: To evaluate an optical coherence tomography (OCT)-guided, variable-dosing regimen with intravitreal ranibizumab for the treatment of patients with neovascular age-related macular degeneration (AMD).
DESIGN: Open-label, prospective, single-center, nonrandomized, investigator-sponsored clinical study.
METHODS: In this two-year study, neovascular AMD patients with subfoveal choroidal neovascularization (CNV) (n = 40) and a central retinal thickness of at least 300 mum as measured by OCT were enrolled to receive three consecutive monthly intravitreal injections of ranibizumab (0.5 mg). Thereafter, retreatment with ranibizumab was performed if one of the following changes was observed between visits: a loss of five letters in conjunction with fluid in the macula as detected by OCT, an increase in OCT central retinal thickness of at least 100 mum, new-onset classic CNV, new macular hemorrhage, or persistent macular fluid detected by OCT at least one month after the previous injection of ranibizumab.
RESULTS: At month 12, the mean visual acuity improved by 9.3 letters (P < .001) and the mean OCT central retinal thickness decreased by 178 mum (P < .001). Visual acuity improved 15 or more letters in 35% of patients. These visual acuity and OCT outcomes were achieved with an average of 5.6 injections over 12 months. After a fluid-free macula was achieved, the mean injection-free interval was 4.5 months before another reinjection was necessary.
CONCLUSION: This OCT-guided, variable-dosing regimen with ranibizumab resulted in visual acuity outcomes similar to the Phase III clinical studies, but required fewer intravitreal injections. OCT appears useful for determining when retreatment with ranibizumab is necessary.

Référence : Am J Ophthalmol. 2007 Apr;143(4):566-583. An Optical Coherence Tomography-Guided, Variable Dosing Regimen with Intravitreal Ranibizumab (Lucentis) for Neovascular Age-related Macular Degeneration. Fung AE, Lalwani GA, Rosenfeld PJ, Dubovy SR, Michels S, Feuer WJ, Puliafito CA, Davis JL, Flynn HW Jr, Esquiabro M.

Conditionnement du Lucentis

La dose recommandée par injection intra-vitréenne de Lucentis, selon l’AMM, est de 0,5 mg.

La présentation galénique du Lucentis est un flacon contenant 3 ml de solution à 10 mg/ml.
Sur ces 3 ml donc, seuls 0,05 ml seront effectivement injectés dans l’oeil…
Bien sûr, il convient de prélever un peu plus dans le flacon afin de purger la seringue et l’aiguille de toute bulle d’air…
Or, il me semble que 1,5 ml suffisent largement pour purger confortablement et avoir 0,05 ml à injecter !

Donc, en conditionnant différemment le Lucentis (flacon de 1,5 ml, voire seringue préremplie), la quantité de médicament fournie pour chaque injection pourrait être divisée par deux… et le prix aussi ?

Avastin vs. Lucentis dans Wall Street Journal

Lecture utile en complément de l’article du Figaro du 19 février, ce long article du Wall Street Journal du 22 février 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 :

  • l’impact financier de l’utilisation de l’un ou l’autre des traitements, pour les patients ou la collectivité d’une part, et le laboratoire d’autre part :
  • 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.

  • le développement du Lucentis, dérivé de l’Avastin :
  • « 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.

  • l’origine de l’utilisation de l’Avastin « off-label » en ophtalmologie :
  • 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.

  • l’équivalence apparente entre les deux traitements, tant sur le plan de l’efficacité qu’en terme de tolérance :
  • 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%).

  • la nécessité d’une étude comparative… et la difficulté de son financement, auquel on ne peut attendre aucune aide des firmes pharmaceutiques :
  • 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.

    Risque d’accident vasculaire cérébral et Lucentis : précisions

    Fin janvier, Genentech avait diffusé aux prescripteurs de Lucentis les résultats d’une analyse intermédiaire de l’étude SAILOR, qui montraient une différence statistiquement significative pour l’incidence des accidents vasculaires cérébraux (AVC) entre un groupe traité par 0.3 mg et un autre traité par 0.5 mg (taux d’AVC respectifs de 1.2% et 0.3%), ces taux restant cependant « cohérents avec les études cliniques pivots, et ne sont pas plus élevées que le taux d’AVC dans la population générale d’âge et profil similaire ». Par ailleurs, les patients aux antécédents d’AVC présentaient un risque plus élevé de récidive d’AVC.

    Dans un courrier daté du 23 février, Novartis donne les résultats d’une nouvelle analyse intermédiaire (données cloturées au 10 janvier 2007) :

    Dans cette nouvelle analyse, le déséquilibre concernant l’incidence des AVC entre le groupe recevant Lucentis à la dose de 0.5 mg par rapport à celui recevant Lucentis à 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 à la dose de 0.5 mg et 0.3 mg.

    En attendant les résultats finaux de cette étude (deuxième semestre 2007), qui seuls permettront de conclure, il est certainement prudent de vérifier les antécédents d’AVC des patients susceptibles de recevoir Lucentis…

    Avastin et Lucentis dans le Figaro

    Un article paru ce matin dans le Figaro pose bien le dilemme auquel nous sommes confrontés au moment du choix d’un anti-VEGF pour nos patients atteints de DMLA : soit un médicament validé par de sérieuses études randomisées mais vendu plus de 1200€ par injection, soit la « molécule-mère » du précédent (fabriquée par le même laboratoire), utilisée largement en raison de son prix 30 fois moindre, mais non « validée » pour un usage intra-oculaire… :

    Continue la lecture