Strong safety and efficacy support approval in CLL
We attended the oral data presentation of Genmab’s ofatumumab phase III trial in relapsed/refractory CLL (a blood cancer) at the ASH clinical meeting. The data, described as "quite stunning" by a leading CLL clinician, showed impressive response rates across all patient subgroups, including patients previously exposed to Rituxan, another antibody commonly used to treat CLL. Clinicians also thought ofatumumab was safe and well tolerated. In our view the data strongly support approval of ofatumumab in relapsed/refractory CLL, for which Genmab and partner GSK plan to file in January 2009. We have increased our CLL peak sales forecasts from $350mn to $500mn and upgrade to Buy from Neutral.
High response rates across patient subgroups
Response rates were consistently high in all patient subgroup analyses performed (47-50+%), including prior exposure to the Rituxan. 54% of double refractory (DR) patients previously exposed to Rituxan achieved a response vs. 63% of those not exposed. The response rates in the Campath-ineligible (BFR) group were 44%
and 50%. It is not clear whether ofatumumab is effective in Rituxan refractory patients, however, as it is difficult to discern whether patients were refractory to the chemotherapy or to Rituxan itself.
Safety profile benign, impressive survival
Clinicians we spoke to had no concerns about ofatumumab's safety profile, and most thought it was comparable to Rituxan's. The 25% infection rate was not seen as an issue, as late-stage CLL patients are generally immunosuppressed and hence highly susceptible to infections regardless of therapy. Clinicians were both
surprised and impressed by the high response rates achieved. Historical analysis and their own data demonstrate that these patients do not respond to antibody therapy and survive for only 9-10 months (vs. 14-15 months in this study).
Duration of response slightly disappointing to some
Patients who responded to ofatumumab maintained their response for 6-7 months and experienced progression-free survival (PFS) of 5.7 (DR) and 5.9 (BFR) months. While this is well above the 3-4 months indicated by FDA for approval, some clinicians voiced disappointment, particularly given the strength of the response rates. However, it needs to be taken into account that the study enrolled
a very challenging patient population.
Upgrading to Buy from Neutral; PO unchanged at DKK325
Both the quality of the clinical data presented at ASH and clinicians’ reception of the data exceeded our expectations. Even though we see some potential longer term risks regarding commercial success in other indications (eg rheumatoid arthritis), we expect the shares to perform well over the near term.
We attended the oral data presentation of Genmab’s ofatumumab phase III trial in relapsed/refractory CLL (a blood cancer) at the ASH clinical meeting. The data, described as "quite stunning" by a leading CLL clinician, showed impressive response rates across all patient subgroups, including patients previously exposed to Rituxan, another antibody commonly used to treat CLL. Clinicians also thought ofatumumab was safe and well tolerated. In our view the data strongly support approval of ofatumumab in relapsed/refractory CLL, for which Genmab and partner GSK plan to file in January 2009. We have increased our CLL peak sales forecasts from $350mn to $500mn and upgrade to Buy from Neutral.
High response rates across patient subgroups
Response rates were consistently high in all patient subgroup analyses performed (47-50+%), including prior exposure to the Rituxan. 54% of double refractory (DR) patients previously exposed to Rituxan achieved a response vs. 63% of those not exposed. The response rates in the Campath-ineligible (BFR) group were 44%
and 50%. It is not clear whether ofatumumab is effective in Rituxan refractory patients, however, as it is difficult to discern whether patients were refractory to the chemotherapy or to Rituxan itself.
Safety profile benign, impressive survival
Clinicians we spoke to had no concerns about ofatumumab's safety profile, and most thought it was comparable to Rituxan's. The 25% infection rate was not seen as an issue, as late-stage CLL patients are generally immunosuppressed and hence highly susceptible to infections regardless of therapy. Clinicians were both
surprised and impressed by the high response rates achieved. Historical analysis and their own data demonstrate that these patients do not respond to antibody therapy and survive for only 9-10 months (vs. 14-15 months in this study).
Duration of response slightly disappointing to some
Patients who responded to ofatumumab maintained their response for 6-7 months and experienced progression-free survival (PFS) of 5.7 (DR) and 5.9 (BFR) months. While this is well above the 3-4 months indicated by FDA for approval, some clinicians voiced disappointment, particularly given the strength of the response rates. However, it needs to be taken into account that the study enrolled
a very challenging patient population.
Upgrading to Buy from Neutral; PO unchanged at DKK325
Both the quality of the clinical data presented at ASH and clinicians’ reception of the data exceeded our expectations. Even though we see some potential longer term risks regarding commercial success in other indications (eg rheumatoid arthritis), we expect the shares to perform well over the near term.
så må Erica altså bide i det sure æble. Genmab handles i 256, latterligt billigt. Håber bare at de institutionelle nu vil købe op
Så de gjorde det altså. Markedsføringen begyndte og lykkedes. Nu skal vi bare have det stof på banen
Det er så vigtigt en indikation, den ASH præsentation, netop fordi lægerne sidder dernede. Der er i mit sind ingen tvivl om at dette stof ville blive revet ned af hylderne for Late Stage patienter. Så hele det markedet skal nok blive penetreret hurtigt. Spørgsmålet er om man kan bruge det off-label til first stage? det kan man vel ikke. Hvad siger du trolmand??
9/12 2008 12:31 troldmanden 0
535 Uden at have specielt meget kendskab til kræft området så plejer der dog at være en hel del amerikanske læger der forsøger sig med off label indikationer. Men det afhænger selvfølgelig meget af hvor solide data er, og ikke mindst hvor sikkert et givent stof er.
Omkring sikkerheden så kan det måske godt vise sig at blive et problem at der var en patient der fik PML. Det er en alvorlig og potentiel livstruende sygdom. Og det er noget myndighederne vil se MEGET alvorligt på i behandling af ikke dødelige sygdomme. Så derfor giver de nye data nogle ridser i lakken hvad angår RA og psoriasis.
Hvis hyppigheden af PML ender med at blive en ud af 100-150 så bliver stoffet ikke godkendt i disse indikationer og dermed halveres det potentielle salg......
Omkring sikkerheden så kan det måske godt vise sig at blive et problem at der var en patient der fik PML. Det er en alvorlig og potentiel livstruende sygdom. Og det er noget myndighederne vil se MEGET alvorligt på i behandling af ikke dødelige sygdomme. Så derfor giver de nye data nogle ridser i lakken hvad angår RA og psoriasis.
Hvis hyppigheden af PML ender med at blive en ud af 100-150 så bliver stoffet ikke godkendt i disse indikationer og dermed halveres det potentielle salg......
1. Hvad skal de taler om ved telekonferencen idag? Kan der komme en hel stor nyhed?? Er der noget bedre tidspunkt for en takeover end nu??
2. Opjustering fra west lb til salg på 2,5-3 mia dkk i 2012. Synes dog det er lidt lavt, men dog alligevel rimeligt vildt taget dagens kurs i betragtning. Er dette kun for refractory patienter. Vi ved hele markedt for rituxian ligger i omegnen af 25-35 mia dkk. Jeg tror på at Arzerra får en væsentligt andel af markedet.
2. Opjustering fra west lb til salg på 2,5-3 mia dkk i 2012. Synes dog det er lidt lavt, men dog alligevel rimeligt vildt taget dagens kurs i betragtning. Er dette kun for refractory patienter. Vi ved hele markedt for rituxian ligger i omegnen af 25-35 mia dkk. Jeg tror på at Arzerra får en væsentligt andel af markedet.
9/12 2008 12:35 troldmanden 0537 Her er data fra Roches 3. generations CD20. Omend der kun er tale om et lille fase 1/2 studie så er det dog ret interessant at der er 205 (4 patienter) der oplever CR. Jeg kan forstå fase 3 HTH med Rituximab vil starte ultimo 09
08.12.2008 | 16:08 Uhr
First Glycoengineered, Humanized, Type II CD20 Monoclonal Antibody to Enter Clinical Trials Could Offer Hope for Difficult to Treat Lymphoma Patients
Basel, Switzerland (ots/PRNewswire) - - For Non-US Media Only
- Abstract 234
- Roche and GlycArt Showcase Promising Early Results for its Next-Generation Lymphoma Treatment, R7159/GA101
Data presented for the first time today, at the 50th Annual Meeting of the American Society of Hematology (ASH), show that R7159/GA101, a new monoclonal CD20 antibody in development, could offer powerful benefits in treating patients with relapsed or refractory types of CD20 positive non-Hodgkin's lymphoma (NHL), recognised as a difficult to treat patient population.
Results from the phase I, dose escalation portion of this phase I/IIa study demonstrate that of the 21 heavily pre-treated B-cell NHL patients that were enrolled (3 median prior therapies), nine showed an objective response to treatment with R7159/GA101 monotherapy. Of these, four patients were regarded as being in complete remission following treatment, and five experienced a partial response. A further five showed stabilization of their disease. Of the 11 patients whose treatment had included prior hematopoietic stem cell transplant (transplant of stem cells from the bone marrow to produce new blood cells), six were responders. As well as demonstrating strong efficacy data, the results also indicate that R7159/GA101 is well tolerated.
"There are undoubtedly excellent lymphoma treatments already in existence, but some patients still fail to be cured," said Professor Gilles Salles, Centre Hospitalier Lyon-Sud, France and lead investigator of the study. "We need to continue to look to the future so that we can offer patients innovative treatments for every stage of lymphoma. R7159/ GA101 is the first in a new class of anti-CD20 antibodies to enter clinical trials and, so far, the results are really very encouraging indeed. We are eager to pursue clinical trials with R7159/GA101, as single agent or combined with chemotherapy, to further characterize its activity in B-cell lymphoma."
This data presented at ASH will be supplemented by further dosing studies and further clinical data is expected in 2009.
"Although GA101 is still in the early stages of development, we are excited by these early data," said Manfred Heinzer, Head Strategic Marketing Oncology, Roche. "MabThera has revolutionised the management of NHL, with over 1.5 million people treated with the drug to date and we hope that R7159/ GA101 will provide another option for those patients requiring more therapeutic choices."
About the study
The study is a phase I/IIa study designed to assess R7159/GA101 in patients with CD20+ malignant disease. 21 NHL patients, 20 of whom previously received MabThera (rituximab) have been involved the phase I dose escalation portion of the study. The endpoints in the phase I portion included safety and tolerability, dose-limiting toxicity, pharmacokinetics, preliminary efficacy. The phase II portion in NHL is now recruiting.
A dose escalation in CLL patients has been performed separately in this study and will be reported later. The safety profile of R7159/GA101 has been shown to be very similar to that of rituximab.
About R7159/ GA101
R7159/GA101 is the first humanised and glycoengineered monoclonal anti-CD20 antibody to enter clinical trials. It is a novel type II anti-CD20 antibody with increased direct cell death vs rituximab and enhanced ADCC. R7159/GA101 has shown a similar safety profile to MabThera (rituximab) and promising efficacy in patients with CD20-positive malignant disease. Preclinical in vivo lymphoma models show that R7159/GA101 has superior efficacy to MabThera.
08.12.2008 | 16:08 Uhr
First Glycoengineered, Humanized, Type II CD20 Monoclonal Antibody to Enter Clinical Trials Could Offer Hope for Difficult to Treat Lymphoma Patients
Basel, Switzerland (ots/PRNewswire) - - For Non-US Media Only
- Abstract 234
- Roche and GlycArt Showcase Promising Early Results for its Next-Generation Lymphoma Treatment, R7159/GA101
Data presented for the first time today, at the 50th Annual Meeting of the American Society of Hematology (ASH), show that R7159/GA101, a new monoclonal CD20 antibody in development, could offer powerful benefits in treating patients with relapsed or refractory types of CD20 positive non-Hodgkin's lymphoma (NHL), recognised as a difficult to treat patient population.
Results from the phase I, dose escalation portion of this phase I/IIa study demonstrate that of the 21 heavily pre-treated B-cell NHL patients that were enrolled (3 median prior therapies), nine showed an objective response to treatment with R7159/GA101 monotherapy. Of these, four patients were regarded as being in complete remission following treatment, and five experienced a partial response. A further five showed stabilization of their disease. Of the 11 patients whose treatment had included prior hematopoietic stem cell transplant (transplant of stem cells from the bone marrow to produce new blood cells), six were responders. As well as demonstrating strong efficacy data, the results also indicate that R7159/GA101 is well tolerated.
"There are undoubtedly excellent lymphoma treatments already in existence, but some patients still fail to be cured," said Professor Gilles Salles, Centre Hospitalier Lyon-Sud, France and lead investigator of the study. "We need to continue to look to the future so that we can offer patients innovative treatments for every stage of lymphoma. R7159/ GA101 is the first in a new class of anti-CD20 antibodies to enter clinical trials and, so far, the results are really very encouraging indeed. We are eager to pursue clinical trials with R7159/GA101, as single agent or combined with chemotherapy, to further characterize its activity in B-cell lymphoma."
This data presented at ASH will be supplemented by further dosing studies and further clinical data is expected in 2009.
"Although GA101 is still in the early stages of development, we are excited by these early data," said Manfred Heinzer, Head Strategic Marketing Oncology, Roche. "MabThera has revolutionised the management of NHL, with over 1.5 million people treated with the drug to date and we hope that R7159/ GA101 will provide another option for those patients requiring more therapeutic choices."
About the study
The study is a phase I/IIa study designed to assess R7159/GA101 in patients with CD20+ malignant disease. 21 NHL patients, 20 of whom previously received MabThera (rituximab) have been involved the phase I dose escalation portion of the study. The endpoints in the phase I portion included safety and tolerability, dose-limiting toxicity, pharmacokinetics, preliminary efficacy. The phase II portion in NHL is now recruiting.
A dose escalation in CLL patients has been performed separately in this study and will be reported later. The safety profile of R7159/GA101 has been shown to be very similar to that of rituximab.
About R7159/ GA101
R7159/GA101 is the first humanised and glycoengineered monoclonal anti-CD20 antibody to enter clinical trials. It is a novel type II anti-CD20 antibody with increased direct cell death vs rituximab and enhanced ADCC. R7159/GA101 has shown a similar safety profile to MabThera (rituximab) and promising efficacy in patients with CD20-positive malignant disease. Preclinical in vivo lymphoma models show that R7159/GA101 has superior efficacy to MabThera.
9/12 2008 13:06 Solsen 0538 Nu er CLL kendt for ikke at udtrykke CD20 særlig kraftigt - derfor vil CR være mere sandsynlig i NHL - mener ikke Rituxan nogen sinde har give CR i CLL i disse senstadiepatienter.
Men PML kan give mig kuldegysninger, idet det er hvad jeg har frygtet - Tysabri blev forsinket meget pga. mistanke omkring årsag til denne sygdom i et par patienter med MS - latent virus der vækkes til live i patienter med lav immunstatus. Rituxan fremkalder også PML.
Denne patientgruppe er meget udsatte og det kan være forklaringen - det kunne blive et hot emne på dagens CC
Men PML kan give mig kuldegysninger, idet det er hvad jeg har frygtet - Tysabri blev forsinket meget pga. mistanke omkring årsag til denne sygdom i et par patienter med MS - latent virus der vækkes til live i patienter med lav immunstatus. Rituxan fremkalder også PML.
Denne patientgruppe er meget udsatte og det kan være forklaringen - det kunne blive et hot emne på dagens CC
9/12 2008 13:26 troldmanden 0539 ok var ikke klar over at Rituxan også kan give PML i enkelte tilfælde.
I cancer indikationerne bliver det ikke noget problem. Men i alle andre indikationer komplicere det her uden tvivl casen
I cancer indikationerne bliver det ikke noget problem. Men i alle andre indikationer komplicere det her uden tvivl casen
9/12 2008 13:32 Solsen 0540 http://en.wikipedia.org/wiki/Progressive_multifocal_leukoencephalopathy
Ja heldigvis er det ikke set tidligere !
Ja heldigvis er det ikke set tidligere !
9/12 2008 14:31 Solsen 0544 linket virker ikke:
December 19, 2006 — The US Food and Drug Administration (FDA) is warning healthcare professionals regarding the risk for progressive multifocal leukoencephalopathy (PML) in patients receiving rituximab intravenous infusion (Rituxan, made by Genentech, Inc, and Biogen Idec, Inc) for the treatment of systemic lupus erythematosus (SLE), an off-label indication.
The warning was based on 2 fatal cases of PML in patients with SLE receiving rituximab, according to an alert sent today from MedWatch, the FDA's safety information and adverse event reporting program. The drug manufacturers estimate that approximately 10,000 patients with SLE have received rituximab therapy.
PML is a rare and frequently fatal demyelinating disease of the central nervous system that primarily affects patients whose immune systems are compromised by disease or medical treatments. It is caused by reactivation of the JC virus, which remains latent in up to 80% of healthy adults. There are no known effective treatments for PML.
The first death occurred during March 2006 in a woman aged 70 years with a history of lupus nephritis and hemolytic anemia. She had received prior treatment with cyclophosphamide, azathioprine, and long-term corticosteroid therapy. After receiving multiple infusions of rituximab (4 in 2004 and 2 in 2005), she developed vertigo, tongue biting, and difficulty walking. Magnetic resonance imaging (MRI) revealed multiple brain lesions, and brain autopsy showed characteristics of PML.
The second death, in July 2006, involved a woman aged 45 years with a 24-year history of SLE and prior treatment with cyclophosphamide and intravenous methylprednisolone. After receiving 3 courses of rituximab from 2002 to 2005, she developed neurologic signs and symptoms. MRI revealed multiple brain lesions, and tests of cerebrospinal fluid were positive for JC virus.
Because rituximab targets CD20-positive lymphocytes, its use is associated with an increased vulnerability to infection regardless of the indication. Postmarketing reports of serious viral illness have included 23 confirmed cases of PML in patients with lymphoid malignancies either during treatment or as long as 1 year after the last dose. The FDA notes that the majority of affected patients had also received other immunosuppressive drugs.
Healthcare professionals are advised to maintain a high index of suspicion for PML in patients receiving rituximab therapy, particularly those who develop new neurologic signs or symptoms.
Patients receiving rituximab therapy should be advised to promptly contact their healthcare professional if they develop any major changes in vision, balance/coordination, or experience disorientation/confusion.
Rituximab intravenous infusion is approved for use in combination with methotrexate to reduce signs and symptoms of moderately to severely active rheumatoid arthritis in adults who have had an inadequate response to one or more tumor necrosis factor–alpha inhibitor therapies.
It is also indicated for use with cyclophosphamide, vincristine, and prednisolone chemotherapy in the first-line treatment of follicular, CD20-positive B-cell non-Hodgkin's lymphoma (NHL), and for the treatment of low-grade NHL in patients with stable disease who achieve a partial or complete response to first-line treatment with CVP chemotherapy.
In addition, rituximab can be used for the treatment of patients with relapsed or refractory low-grade or follicular CD20-positive B-cell NHL, and for the first-line treatment of CD20-positive diffuse large B-cell non-Hodgkin's lymphoma in combination with cyclophosphamide, doxorubicin, vincristine, and prednisone or other anthracycline-based chemotherapy regimens.
Adverse events potentially related to rituximab therapy, including PML, should be reported to the FDA's MedWatch reporting program by phone at 1-800-FDA-1088, by fax at 1-800-FDA-0178, online at http://www.fda.gov/medwatch, or by mail to 5600 Fishers Lane, Rockville, MD 20852-9787.
December 19, 2006 — The US Food and Drug Administration (FDA) is warning healthcare professionals regarding the risk for progressive multifocal leukoencephalopathy (PML) in patients receiving rituximab intravenous infusion (Rituxan, made by Genentech, Inc, and Biogen Idec, Inc) for the treatment of systemic lupus erythematosus (SLE), an off-label indication.
The warning was based on 2 fatal cases of PML in patients with SLE receiving rituximab, according to an alert sent today from MedWatch, the FDA's safety information and adverse event reporting program. The drug manufacturers estimate that approximately 10,000 patients with SLE have received rituximab therapy.
PML is a rare and frequently fatal demyelinating disease of the central nervous system that primarily affects patients whose immune systems are compromised by disease or medical treatments. It is caused by reactivation of the JC virus, which remains latent in up to 80% of healthy adults. There are no known effective treatments for PML.
The first death occurred during March 2006 in a woman aged 70 years with a history of lupus nephritis and hemolytic anemia. She had received prior treatment with cyclophosphamide, azathioprine, and long-term corticosteroid therapy. After receiving multiple infusions of rituximab (4 in 2004 and 2 in 2005), she developed vertigo, tongue biting, and difficulty walking. Magnetic resonance imaging (MRI) revealed multiple brain lesions, and brain autopsy showed characteristics of PML.
The second death, in July 2006, involved a woman aged 45 years with a 24-year history of SLE and prior treatment with cyclophosphamide and intravenous methylprednisolone. After receiving 3 courses of rituximab from 2002 to 2005, she developed neurologic signs and symptoms. MRI revealed multiple brain lesions, and tests of cerebrospinal fluid were positive for JC virus.
Because rituximab targets CD20-positive lymphocytes, its use is associated with an increased vulnerability to infection regardless of the indication. Postmarketing reports of serious viral illness have included 23 confirmed cases of PML in patients with lymphoid malignancies either during treatment or as long as 1 year after the last dose. The FDA notes that the majority of affected patients had also received other immunosuppressive drugs.
Healthcare professionals are advised to maintain a high index of suspicion for PML in patients receiving rituximab therapy, particularly those who develop new neurologic signs or symptoms.
Patients receiving rituximab therapy should be advised to promptly contact their healthcare professional if they develop any major changes in vision, balance/coordination, or experience disorientation/confusion.
Rituximab intravenous infusion is approved for use in combination with methotrexate to reduce signs and symptoms of moderately to severely active rheumatoid arthritis in adults who have had an inadequate response to one or more tumor necrosis factor–alpha inhibitor therapies.
It is also indicated for use with cyclophosphamide, vincristine, and prednisolone chemotherapy in the first-line treatment of follicular, CD20-positive B-cell non-Hodgkin's lymphoma (NHL), and for the treatment of low-grade NHL in patients with stable disease who achieve a partial or complete response to first-line treatment with CVP chemotherapy.
In addition, rituximab can be used for the treatment of patients with relapsed or refractory low-grade or follicular CD20-positive B-cell NHL, and for the first-line treatment of CD20-positive diffuse large B-cell non-Hodgkin's lymphoma in combination with cyclophosphamide, doxorubicin, vincristine, and prednisone or other anthracycline-based chemotherapy regimens.
Adverse events potentially related to rituximab therapy, including PML, should be reported to the FDA's MedWatch reporting program by phone at 1-800-FDA-1088, by fax at 1-800-FDA-0178, online at http://www.fda.gov/medwatch, or by mail to 5600 Fishers Lane, Rockville, MD 20852-9787.
