Genmab

http://www.atv.dk/index.php?lang=1&c=news&id=315 Til interesserede .... og kan I huske, at NOVO har talt om 3. ben og 10 mia biotekkøb !

Epidermal Growth Factor Receptor (EGFR) Antibody-Induced Antibody-Dependent Cellular Cytotoxicity Plays a Prominent Role in Inhibiting Tumorigenesis, Even of Tumor Cells Insensitive to EGFR Signaling Inhibition Marije B. Overdijk*, Sandra Verploegen*, Jeroen H. van den Brakel*, Jeroen J. Lammerts van Bueren*, Tom Vink*, Jan G. J. van de Winkel*†, Paul W. H. I. Parren* and Wim K. Bleeker* Ab-dependent cellular cytotoxicity (ADCC) is recognized as a prominent cytotoxic mechanism for therapeutic mAbs in vitro. However, the contribution of ADCC to in vivo efficacy, particularly for treatment of solid tumors, is still poorly understood. For zalutumumab, a therapeutic epidermal growth factor receptor (EGFR)-specific mAb currently in clinical development, previous studies have indicated signaling inhibition and ADCC induction as important therapeutic mechanisms of action. To investigate the in vivo role of ADCC, a panel of EGFR-specific mAbs lacking specific functionalities was generated. By comparing zalutumumab with mAb 018, an EGFR-specific mAb that induced ADCC with similar potency, but did not inhibit signaling, we observed that ADCC alone was insufficient for efficacy against established A431 xenografts. Interestingly, however, both zalutumumab and mAb 018 prevented tumor formation upon early treatment in this model. Zalutumumab and mAb 018 also completely prevented outgrowth of lung metastases, in A431 and MDA-MB-231-luc-D3H2LN experimental metastasis models, already when given at nonsaturating doses. Finally, tumor growth of mutant KRAS-expressing A431 tumor cells, which were resistant to EGFR signaling inhibition, was completely prevented by early treatment with zalutumumab and mAb 018, whereas ADCC-crippled N297Q-mutated variants of both mAbs did not show any inhibitory effects. In conclusion, ADCC induction by EGFR-specific mAbs represents an important mechanism of action in preventing tumor outgrowth or metastasis in vivo, even of cancers insensitive to EGFR signaling inhibition. The Journal of Immunology, 2011, 187: 000–000.

Anti-CD38 antibodies or antibody variants have been shown to provide therapeutics for the treatment of CD38-positive hematological malignancies.3, 4, 5, 6, 7 Introduction of the antibody against CD38 may, however, raise concerns of side effects such as an infusion reaction and pharmacological phenomena associated with the long half-life of the antibody. Although antibodies against CD38 have been administered to patients with myeloma or B-cell lymphoma, there has been no report of adverse effects.7, 8 Indeed, daratumumab, a novel therapeutic human CD38 antibody and humanized monoclonal CD38 antibody (SAR650984) (http://clinicaltrialsfeeds.org /clinical-trials/show/NCT01084252), is currently in clinical trials. This therapeutic option could be ready for use anytime without manipulation of cells and may be useful for most myeloma patients. http://www.nature.com/leu/journal/vaop/ncurrent/full/leu2011205a.html

Se også denne: http://onlinelibrary.wiley.com/doi/10.1002/pbc.23187/full

Link: http://ard.bmj.com/content/early/2011/08/22/ard.2011.151522.abstract

Results At week 24, a greater proportion of patients on ofatumumab compared with placebo achieved an ACR20 response (50% vs 27%, p<0.001) and a good or moderate EULAR response (67% vs 41%, p<0.001). All other key secondary efficacy endpoints were significantly improved on ofatumumab. Efficacy observed by 8 weeks was sustained throughout the study. The most common AE for ofatumumab versus placebo were rash (21% vs <1%) and urticaria (12% vs <1%), mostly occurring on the first infusion day. Overall, first-dose infusion reactions were 68% for ofatumumab and 6% for placebo, mostly mild to moderate; second-dose infusion reactions markedly declined (<1% and 0%). Serious AE were reported in 5% of ofatumumab versus 3% of placebo patients. Infection rates were 32% and 26% (serious infections <1% and 2%), respectively. One death (interstitial lung disease), unrelated to study drug, was reported on ofatumumab. No antidrug antibodies were detected in ofatumumab patients.

Published Online First 22 August 2011 Abstract Objectives To evaluate the efficacy and safety of intravenous ofatumumab, a fully human anti-CD20 monoclonal antibody, in biological-naive, active rheumatoid arthritis (RA) patients despite methotrexate treatment. Methods In this double-blind, placebo-controlled, phase III study, active RA patients on stable methotrexate were randomly assigned to one course of two infusions of ofatumumab 700 mg (n=130) or placebo (n=130), 2 weeks apart. The primary endpoint was the ACR20 response at week 24. Secondary endpoints included ACR50/70, EULAR response, disease activity score based on 28 joints using C-reactive protein, adverse events (AE) and immunogenicity. Results At week 24, a greater proportion of patients on ofatumumab compared with placebo achieved an ACR20 response (50% vs 27%, p<0.001) and a good or moderate EULAR response (67% vs 41%, p<0.001). All other key secondary efficacy endpoints were significantly improved on ofatumumab. Efficacy observed by 8 weeks was sustained throughout the study. The most common AE for ofatumumab versus placebo were rash (21% vs <1%) and urticaria (12% vs <1%), mostly occurring on the first infusion day. Overall, first-dose infusion reactions were 68% for ofatumumab and 6% for placebo, mostly mild to moderate; second-dose infusion reactions markedly declined (<1% and 0%). Serious AE were reported in 5% of ofatumumab versus 3% of placebo patients. Infection rates were 32% and 26% (serious infections <1% and 2%), respectively. One death (interstitial lung disease), unrelated to study drug, was reported on ofatumumab. No antidrug antibodies were detected in ofatumumab patients. Conclusions Ofatumumab significantly improved all clinical outcomes in biological-naive, active RA patients with no detectable immunogenicity at week 24. No unexpected safety findings were identified. Trial Registry clinical trials.gov registration number NCT00611455

Fra Dahanca (fra 24. marts 2011) DAHANCA 19 Der er indgået 412 patienter og antagelsen er, at studiet kan lukke foråret 2012. Generelt halter det med registrering af primær behandling og follow up.

Efterhånden er ganske mange studier på Clinical Trials opdateret til at have fuldt optag (aktive, men ikke længere rekrutterende): Active, not recruiting Ofatumumab Dose-finding in RRMS Patients Condition: Relapsing Remitting Multiple Sclerosis Intervention: Drug: ofatumumab/placebo Phases: Phase I / Phase II Last Updated Date: May 20, 2010 Primary Completion Date: September 2010 Active, not recruiting Ofatumumab + Chlorambucil vs Chlorambucil Monotherapy in Previously Untreated Patients With Chronic Lymphocytic Leukemia Condition: Chronic Lymphocytic Leukemia (CLL), Untreated Interventions: Drug: chlorambucil, tablets; Drug: ofatumumab (GSK1841157) infusion Phase: Phase III Last Updated Date: August 25, 2011 Primary Completion Date: March 2013 Active, not recruiting A Phase II Trial of Ofatumumab in Subjects With Waldenstrom's Macroglobulinemia Conditions: Waldenstrom's Macroglobulinemia; Waldenstrom Macroglobulinaemia Intervention: Biological: Ofatumumab Phase: Phase II Last Updated Date: August 11, 2011 Primary Completion Date: March 2013 Active, not recruiting Ofatumumab Retreatment and Maintenance Treatment in CLL Patients Condition: B-Cell Chronic Lymphocytic Leukemia Intervention: Drug: Ofatumumab Phase: Phase II Last Updated Date: July 21, 2011 Primary Completion Date: February 2012 Active, not recruiting Lenalidomide and Ofatumumab in Previously Treated Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma (CLL/SLL) Conditions: Chronic Lymphocytic Leukemia; Small Lymphocytic Lymphoma Interventions: Drug: Lenalidomide; Drug: Ofatumumab Phase: Phase II Last Updated Date: July 14, 2011 Primary Completion Date: November 2013 Active, not recruiting A Phase I/II, a Single Arm, Open-label Study of Ofatumumab (GSK1841157) in Patients With Previously Treated Chronic Lymphocytic Leukemia Condition: Leukaemia, Lymphocytic, Chronic Intervention: Drug: ofatumumab 100 mg, 1000 mg / vial Phase: Phase II Last Updated Date: April 21, 2011 Primary Completion Date: June 2011 Active, not recruiting Study to Evaluate the Efficacy and Safety of Treatment With Bendamustine in Combination With Ofatumumab in Previously Untreated Patients With Indolent B-Cell Non-Hodgkin's Lymphoma (NHL) Condition: Non-Hodgkin's Lymphoma (NHL) Intervention: Drug: Bendamustine and Ofatumumab Phase: Phase II Last Updated Date: April 15, 2011 Primary Completion Date: July 2011 Active, not recruiting Ofatumumab in Patients With Relapsed/Progressive Diffused Large B-Cell Lymphoma (DLBCL) Ineligible for or Relapse/Progression After Transplant Condition: Diffuse Large B Cell Lymphoma (DLBCL) Intervention: Drug: Ofatumumab Phase: Phase II Last Updated Date: July 7, 2011 Primary Completion Date: May 2010

Amy Baldwin attended the BIO International 2011 Convention in Washington, DC as part of the Minnesota delegation. The delegation was comprised of over 50 individuals representing 25 organizations throughout Minnesota. The convention had over 15,000 attendees and 1,900 exhibitors from around the world. While at this convention Ms. Baldwin met with Genmab/PDL’s broker who is working with two to?three parties that have shown an interest in acquiring the property. An acquisition may happen before year end. http://citysearch.brooklynpark.org/currentedaep.pdf

FORTSAT: A total of 27 patients with a median age of 65 (range 48–83) years were treated. The median disease duration was 6 years (range 3–15), with a median number of three previous treatments (range 0–6). 22·2% of patients were Rai stage I–II, the remainder stage III–IV. There were no Binet stage A patients, with 25% being Binet stage B and 75% Binet stage C. Cytogenetic data was available on 24 patients. Six patients had no discernible abnormality, two patients had trisomy 12, two patients del13q14.3, seven patients del11q22.3 and six patients del17p13.1. Twelve patients had bulky refractory disease, four had double refractory disease, five had both bulky refractory and double refractory disease and six were considered unsuitable for Alemtuzumab therapy. Three patients died after receiving one or two infusions. These were classified as non-responders. 11/12 patients, who were red cell dependent prior to Ofatumumab therapy, became transfusion independent. The median time to reach a haemoglobin level >110 g/l was 21 days. Twelve patients had a platelet count 100 × 109/l (Table I). The median follow up was 8·0 months (range 1–23 months) from the onset of the Ofatumumab infusions. Three patients achieved a clinical complete remission (CR) and 10 patients a partial remission (PR). Nine patients had progressive disease, two stable disease and three died. The overall response rate was therefore 48% (13/27). The median time-to-next-treatment (TTNT) when calculated from the first Ofatumumab infusion was 5·5 months (range 1·5–18) (Table I and Fig 1).

Ofatumumab in advanced stage chronic lymphocytic leukaemia: results of the UK named patient compassionate use programme. Article first published online: 12 MAY 2011 We report our ‘real life’ experience of the use of Ofatumumab in chronic lymphocytic leukaemia (CLL) in the UK compassionate use programme. In addition to patients with bulky fludarabine refractory (BF ref) disease (n = 12) or fludarabine and alemtuzumab refractory (FA ref) disease (n = 4), patients unsuitable for alemtuzumab were included (n = 6). 91% of transfusion dependent patients became transfusion independent. The overall response rate (ORR) was 48% (3/27 clinical CR; 10/27 PR). 4/6 patients with TP53 deletion/mutations responded to Ofatumumab. This is the first series of UK patients confirming that single agent Ofatumumab has efficacy in relapsed refractory CLL and will complement on-going clinical studies. Although thought to be an indolent disease of the elderly, a significant number of patients with chronic lymphocytic leukaemia (CLL) develop chemotherapy resistance and die from bone marrow failure and infectious complications. Ofatumumab (HuMax-CD20) is a fully humanized anti-CD20 monoclonal antibody with promising activity in B-cell disorders including CLL. It binds to a different epitope to Rituximab and is thought to confer greater complement-mediated cellular cytotoxicity with some additional antibody-dependent cellular cytotoxicity (Cheson, 2010). A recent interim analysis of the first 138 patients entered into the single arm Phase II study Hx CD20 406, evaluated its safety and efficacy in BF ref or FA ref disease (Wierda et al, 2010). Patients unsuitable for alemtuzumab were excluded. The overall response rate (ORR) was 58% in the FA ref group and 47% in the BF ref group. Perhaps the most significant improvement was in overall survival, which was 13·7 and 15·4 months in the FA ref and BF ref responder groups respectively, compared to 9·8 and 10·2 months in non-responders. The present analysis included patients recruited into the subsequent UK compassionate use programme by five centres after informed consent, which specified that Ofatumumab was not licensed in the UK, was obtained. Twenty-eight patients were screened but only 27 patients received treatment as one patient died before treatment was commenced. Cytogenetic data was available on 24 patients. Ofatumumab [GlaxoSmithKline (GSK), Uxbridge, UK] was given weekly for eight infusions and then monthly to complete 12 infusions. The first infusion was given at a dose of 300 mg with all subsequent doses being 2000 mg. Adverse events were communicated to GSK. Response was evaluated clinically and by blood counts according to the International Workshop on Chronic Lymphocytic Leukemia guidelines (Hallek et al, 2008). Improvement of peripheral blood cytopenias and reduction in red cell and platelet transfusion requirements were recorded. A total of 27 patients with a median age of 65 (range 48–83) years were tre

hvornår kommer genmab regnskab, skulle det ikke komme ud idag ?

Nemlig, og hvis stresstesten baserer sig på, at der vil være fuld dækning minus selvrisiko, så er den test værdiløs !

Noget nyere om det omtalte CORAL kan for eksempel findes her: http://www.asco.org/ascov2/Meetings/Abstracts?&vmview=abst_detail_view&confID=65&abstractID=30637 Citat:"Patients with prior exposure to rituximab had more refractory disease and adverse prognostic factors."

Idag kom så DLBCL indikationen også som skrevet ud. Det er en meget spændende og stor indikation indenfor NHL, hvor der som der står nedenfor ikke rigtigt er fundet en guld standard terapi for relapsed patienter. http://www.haematologica.org/cgi/content/full/93/12/1776 Man er oppe imod 2 med betydeligt lavere ORR i indikationen. Conclusions The treatment paradigm in patients with relapsed and refractory diffuse large B cell lymphoma is still being defined. Outcome after failure of R-CHOP induction chemotherapy continues to be dismal, and efforts to define patients with refractory disease and early relapse will be crucial. Autologous stem cell transplant following high-dose chemotherapy remains the standard of care but will need to be revisited in the post-rituximab era. Salvage therapy of choice and the role of rituximab remain to be elucidated, and the results from the CORAL study are eagerly anticipated. Novel targeted therapeutics are evolving, and further incorporation of these agents into induction or salvage treatments will be the key in future.

til gruppen. Jan kommer og taler for os eksklusivt den 8. august!

Copenhagen, Denmark; July 26, 2011 – Genmab A/S (OMX: GEN) announced today that the Arzerra (ofatumumab) net sales during the second quarter of 2011 were GBP 10.5 million (approximately DKK 88.6 million). This figure consists of net sales in the U.S. of GBP 7.4 million (approximately DKK 62.4 million) and in the rest of the world GBP 3.1 million (approximately DKK 26.2 million). Under the terms of the collaboration with GlaxoSmithKline (GSK), Genmab expects to receive a royalty payment of approximately DKK 17.7 million. http://www.genmab.com/Press Center/RecentNewsReleases/23ArzerraSecondQuarter2011NetSalesFigures.aspx

så det er ikke derfra der vil komme de store påvirkninger....

Jeg mener, at nummer 60 var denne: Anti-CD20 Therapy to Treat Metastatic Melanoma This study is currently recruiting participants. Verified on June 2011 by Medical University of Vienna First Received on June 16, 2011. Last Updated on June 20, 2011 History of Changes Men det er jo efterhånden svært at følge med....