Journal Country: United Kingdom .
Authors: Mascilini F, Amadio G, Di Stefano MG, Ludovisi M, Di Legge A, Conte C, De Vincenzo R, Ricci C, Masciullo V, Salutari V, Scambia G, Ferrandina G .
Date of Publication : 2014 July .
Published in: OncoTargets and Therapy, Vol 2014 // Pp 1273-1284 (2014) .
Clinical Utility of Trabectedin For the Treatment of Ovarian Cancer : Current Evidence.
Abstract :
Among the pharmaceutical options available for treatment of ovarian cancer, attention has been increasingly focused on trabectedin (ET-743), a drug which displays a unique mechanism of action and has been shown to be active in several human malignancies.
Currently, single agent trabectedin is approved for treatment of patients with advanced soft tissue sarcoma after failure of anthracyclines and ifosfamide, and in association with pegylated liposomal doxorubicin for treatment of patients with relapsed partially platinum-sensitive ovarian cancer.
This review aims at summarizing the available evidence about the clinical role of trabectedin in the management of patients with epithelial ovarian cancer.
Novel perspectives coming from a better understanding of trabectedin mechanisms of action and definition of patients subgroups likely susceptible to benefit of trabectedin treatment are also presented.
ZELTIA INFORMA:
PharmaMar inicia un ensayo de fase I con Aplidin® en combinación con bortezomib y dexametasona en pacientes con mieloma múltiple recurrente y/o refractario .
Madrid, 23 de julio del 2014:
Zeltia (Grupo Zeltia, ZEL.MC) ha anunciado hoy que su filial de oncología, PharmaMar SA, ha iniciado un ensayo clínico de fase I con Aplidin® (plitidepsina) en combinación con bortezomib y dexametasona en pacientes con mieloma múltiple recurrente y/o refractario.
El objetivo primario de este estudio es determinar la dosis recomendada de Aplidin® en combinación con bortezomib y dexametasona y evaluar la eficacia de la combinación en pacientes con mieloma múltiple.
El ensayo se llevará a cabo en 6 centros en España y Francia y participarán 30 pacientes.
Una vez se alcance el objetivo de determinar la dosis recomendada, está planeada una expansión de pacientes para evaluar la eficacia de Aplidin® en estadíos más iniciales del tratamiento de la enfermedad.
Este ensayo se enmarca dentro del plan de desarrollo de Aplidin® como una opción temprana de tratamiento para pacientes con mieloma múltiple. El compuesto está también siendo evaluado en un estudio en marcha de fase III para pacientes con mieloma múltiple que hayan recibido, al menos, tres líneas previas de tratamiento.
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* Aplidin® es un agente antitumoral descubierto en el tunicado mediterráneo Aplidium albicans y obtenido actualmente por síntesis química. Es el segundo compuesto más avanzado en desarrollo clínico de PharmaMar.
* Actualmente se encuentra en fase II para neoplasisas malignas sólidas y hematológicas como linfoma de células T y en fase III para mieloma múltiple.
*^Aplidin® ha sido designado fármaco huérfano por la Comisión Europea (CE) y por la Food and Drug Administration (FDA) para múltiple mieloma.
* Aplidin® está licenciado a Chugai Pharmaceutical para copromoción en Europa.
Mariano Barbacid, oncólogo de gran prestigio internacional, ha acudido desanimado a su cita en la Universidad Internacional Menéndez Pelayo de Santander. El motivo lo ha dejado claro nada más comenzar: “Cuando me he enterado de que el Estado ha perdido 13.000 millones de euros con la gestión de Catalunya Banc me han dado ganas de volverme a la cama”. El exdirector del Centro Nacional de Investigaciones Oncológicas (CNIO) ha criticado este martes que mientras se gasta (“o malgasta”) el dinero público en apoyar a las entidades bancarias, los recortes en investigación no cesan.
"Con esa cuantía la ciencia española daría un vuelco”, ha declarado el investigador, que en 1983 descubrió el primer oncogén humano —un gen mutado que provoca cáncer—. Barbacid, que ha ido a la Menéndez Pelayo para participar en unas jornadas sobre biología molecular, ha criticado también que no exista un plan nacional específico para la oncología u otras ramas de la investigación. “A principios de siglo se crearon centros como el IRB (Instituto de Investigación Biomédica), el CSIC (Consejo Superior de Investigaciones Científicas) o el CNIO. Ahora eso se está acabando, hemos perdido el lustre”.
Otra cuestión que preocupa a Barbacid son las pésimas perspectivas para las nuevas generaciones. La edad media del personal del CSIC, por ejemplo, es peligrosamente alta para el ámbito científico: 54 años. La situación, ha lamentado, no va a cambiar en un futuro próximo. “Me produce zozobra la gente joven, personas bien formadas en las que se ha invertido mucho dinero y que ahora no encuentran trabajo ni financiación para sus proyectos. No se ve un final a esta etapa de decadencia en la inversión en I+D”.
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Today's Issue /// 22-07-2014 .
In this sense, says The Pharma Letter’s Spanish correspondent, it is important to note the last announcements they have made during the last weeks, related to new agreements with Spanish GP Pharm, and Japanese Chugai (TYO: 4519, owned 60% by Roche) to buy and sell, respectively, licenses for commercialization of pharmaceuticals products around the world.
With the first of these agreements, PharmaMar bought the license for Politrate (leuproreline), for prostatic cancer, to distribute exclusively in Italy from October. “The goal of this operation is optimizing the commercial structure they have there, taking into account the synergies between the products and our network of sales,” said Luis Mora, general manager of PharmaMar, adding: “We had said before that we are negotiating with other companies to maximize the value of our commercial structures in countries as Italy, and we are going to continue doing the same”.
In the case of Politrate, the Spanish biotech is expecting to gain entrance into a market valued in 35 million euros ($47.3 million), where there are also other competitors. And, anyway, it is not going to have a big impact over its finances, Mora said, remembering the importance of revenues for a small company who needs cash to continue investigating.
Agreement with Chugai
On the other hand, PharmaMar announced a new agreement with Japan’s Chugai, which acquires the license to commercialize Aplidin (plitidepsin) for the treatment of patients with multiple myeloma in eight European countries (France, Germany, UK, Belgium, Netherlands, Luxemburg, Ireland and Austria.
To acquire these rights, Chugai will pay an upfront of 5 million euros, although it could add 30 million euros more according to development, regulatory and commercial milestones. Also, Zeltia’s affiliate will receive royalties from sales and have revenues of selling the products in the rest of European countries (Spain, Italy and Nordics, mainly) where it is going to sell it through its solid commercial structure. It could be possible from the last quarter of 2015, when the company expects all regulatory process could have finish in Europe. “It is important for us receiving the confidence of a company as Chugai, which has put its trust in a product which is still being developed. It creates a good and serious image from PharmaMar,” explained Jose Luis Moreno, responsible for capital markets at PharmaMar.
Nowadays, the product has shown strong data of safety and efficacy, and PharmaMar has recently initiated the Phase III ADMYRE study to confirm it is a valid candidate to treat patients with multiple myeloma. “If final results are positive, it is important to note that European approval it is recognized by other 40 countries, so we are evaluating agreements with other partners to commercialize Aplidin in all of them", said Mr Moreno.
Once again, expert on financials of PharmaMar could not give an exact estimation of the share of the market they could reach with this product, although they calculate it could be near to 300-400 million euros in Europe (Aplidin would be applied in third/quarter line of treatment), taking into account it will compete with other protosome inhibitors and lenalidomide.
PharmaMar’s pipeline: PM01183 :
As has been said before, all resources that PharmaMar can extract from licensing in both directions and with products with low level revenues are thought as useful for financing big innovations with wide indications. One of these, as Moreno pointed out, is PM1183, a new molecular entity that could be used for treatments of several types of cancers.
One proof of that are the results which were presented in American Society of Clinical Oncology annual meeting, held last June in Chicago. In a multicenter Phase II trial, patients with platinum-resistant/refractory ovarian cancer (PRROC) patients received PM1183 in monotherapy, compared with topotecan.
According to data published by PharmaMar, PRROC patients treated with topotecan did not register any objective response, whereas 30% of patients treated with PM1183 exhibited a clinically-significant response. Clinical benefit (objective response or disease stabilization) was observed in 71% of patients treated with PM1183, and in 52% of those who were administered topotecan. Also, median progression free survival in randomized PRROC patients treated with PM1183 was 5.7 months, compared with 1.7 months in patients with topotecan.
Finally, a statistically significant difference of over four months was observed in overall survival between randomized patients treated with PM1183 and those in the control arm. Results could be better because 50% of patients treated with PM1183 are still being monitored for survival. So according to this data, and predictable and manageable safety profile, PharmaMar confirmed that is planning a pivotal Phase III trial with this compound for this indication.