Dice Novartis tener la autorización de la Comisión Europea para Kymriah, aunque en la página de la Ema, a día de hoy, aún aparece como pendiente.
The EC approval is based on the first global CAR-T registration trials, which included patients from eight European countries and demonstrated durable responses and a consistent safety profile in r/r pediatric B-cell ALL and r/r DLBCL.
Novartis is the only company with an approved CAR-T cell therapy for pediatric r/r B-cell ALL and the first to receive approval in two distinct indications, both in the EU and the US
El informe favorable estaría basado en los ensayos clínicos ELIANA para la recidiva de LLA en menores de 25 años:
The EC approval of Kymriah in pediatric and young adult patients with r/r B-cell ALL is based on the pivotal Phase II ELIANA clinical trial, the first pediatric global CAR-T cell therapy registration study for Kymriah in children and young adults with r/r B-cell ALL. ELIANA was conducted in collaboration with the University of Pennsylvania and Children’s Hospital of Philadelphia, evaluating Kymriah in patients in 25 centers in the US, Canada, Australia, Japan, and in Europe, in Austria, Belgium, France, Germany, Italy, Norway and Spain.
In this Novartis-sponsored, global, multi-center study evaluating 75 patients infused with Kymriah with three or more months of follow-up, 81% of patients achieved overall remission (95% CI: 71% - 89%) with 80% of responders still in remission at 6 months. Sixty percent of patients achieved complete response (CR) and 21% of patients achieved CR with incomplete blood count recovery (CRi). Of those patients in remission, 100% had no minimal residual disease (MRD) detected in the bone marrow1. Overall survival (OS) was 90% at six months, and 76% at 12 months. Median OS was 19.1 months (95% CI: 15.2 - NE) in this difficult-to-treat patient population.
y JULIET para los linfomas difusos de células B grandes en adultos:
The EC approval of Kymriah in adult patients with r/r DLBCL is based on the pivotal Phase II JULIET clinical trial, the first multi-center global registration study for Kymriah in adult patients with r/r DLBCL. JULIET was conducted in collaboration with the University of Pennsylvania, and is the largest study examining a CAR-T therapy in DLBCL, enrolling patients from 27 sites in 10 countries across the US, Canada, Australia, Japan, and Europe in Austria, France, Germany, Italy, Norway and the Netherlands.
In the JULIET trial, patients were infused in the inpatient and outpatient setting. In this Novartis-sponsored, global, multi-center study, among 93 evaluable patients who were followed for at least three months or discontinued earlier, Kymriah demonstrated an overall response rate (ORR) of 52% (95% confidence interval [CI], 41% - 62%), with 40% achieving a complete response (CR) and 12% achieving a partial response (PR). The relapse-free probability at 6 and 12 months was 68% and 65%, respectively; and the median duration of response was not reached at the time of data cut-off, indicating sustainability of response1. The OS rate at 12 months was 49% and median OS was 11.7 months among all infused patients (n=111) (95% CI, 6.6-NE).
Hace muy pocos días, el NATIONAL INSTITUTE FOR HEALTH AND CARE EXCELLENCE (NICE) inglés ha publicado un documento para pública consulta sobre la efectiviad de Yescarta en su indicación solicitada: tratamiento de adultos con linfoma difuso de células B grandes o mediástinico primario con fracaso tras al menos dos líneas de tratamientos.
Este documento concluye, de modo provisional:
1.1 Axicabtagene ciloleucel is not recommended, within its anticipated marketing authorisation, for treating relapsed or refractory diffuse large Bcell lymphoma or primary mediastinal large B-cell lymphoma in adults after 2 or more systemic therapies.
1.2 This recommendation is not intended to affect treatment with axicabtagene ciloleucel that was started in the NHS before this guidance was published. People having treatment outside this recommendation may continue without change to the funding arrangements in place for them before this guidance was published, until they and their NHS clinician consider it appropriate to stop. Why the committee made these recommendations
Why the committee made these recommendations
There is no standard treatment for relapsed or refractory diffuse large Bcell lymphoma or primary mediastinal large B-cell lymphoma after 2 or more systemic therapies. Best supportive care is used and usually includes salvage chemotherapy. Evidence from a small, single-arm study suggests that people having axicabtagene ciloleucel have good response rates, overall survival and progression-free survival. But, there are no direct data comparing axicabtagene ciloleucel with salvage chemotherapy (referred to as best supportive care by the company). This means that the exact size of the benefit of axicabtagene ciloleucel compared with salvage chemotherapy is unknown. Axicabtagene ciloleucel meets NICE’s criteria to be considered a lifeextending treatment at the end of life. However, all the cost-effectiveness estimates are above the range normally considered to be a cost-effective use of NHS resources. Axicabtagene ciloleucel does not meet the criteria for inclusion in the Cancer Drugs Fund. Because of this, axicabtagene ciloleucel is not recommended.
The range of the cost-effectiveness estimates is wide and all are above £50,000 per QALY gained
3.23 The company’s deterministic base case showed that the incremental costeffectiveness ratio (ICER) for axicabtagene ciloleucel compared with salvage chemotherapy was over £50,000 per QALY gained. The exact ICER is commercial in confidence and cannot be reported here. The ERG made some changes to the company’s model to reflect its preferred basecase analysis, specifically:
These changes resulted in an ERG exploratory base-case ICER that was over £100,000 per QALY gained. The committee noted the wide range between the company’s and ERG’s base-case ICERs. It agreed that there was a high degree of uncertainty associated with both the company’s and ERG’s estimates because of the limitations in the data for the comparator and the immature survival data for axicabtagene ciloleucel. The committee concluded that based on the data and analyses presented to it, the cost-effectiveness estimates were all above £50,000 per QALY gained.
MolMed ha presentado los resultados del primer semestre de 2018 y en dicho informe se puede leer en la página 33:
Contrariamente alle previsioni, le vendite non sono ancora iniziate né in Italia né in Germania a causa delle difficoltà riscontrate nelle fasi iniziali della commercializzazione del prodotto. Tale situazione è al momento oggetto di un attento esame da parte di MolMed al fine di valutare le opportune azioni da intraprendere, anche in relazione a talune divergenze sorte in merito all’adempimento del contratto di commercializzazione stipulato con Dompé, i cui esiti ad oggi non sono prevedibili.
En la página 20:
ricavi dal prodotto Zalmoxis ® pari a Euro 2.224 migliaia, derivanti dall’accordo di licenza e distribuzione di Zalmoxis® siglato in data 26 luglio 2017 con Dompé e alla vendita del prodotto in regime di fondo Aifa
El informe presenta una descripción amplísima de los riesgos financieros.
A partir de informes anuales y trimestrales he reconstruido la serie de valores trimestrales que abajo se presenta en la gráfica. En el Q4-2017 hay valores "raros" como ventas negativas, pero no encuentro el error si lo hay.
|Datos de ingresos generados por los CART autorizados durante
2018 (millones de dólares)