Genmabs præsentationer på ASCO offentliggjordes her til aften og der ser for så vidt angår Arzerra ikke ud til at være noget spændende i vente, da det alene drejer sig om poster sessions. Zalutumumab derimod præsenteres på en oral session som et "late breaking abstract" så måske får vi endelig lidt mere at vide med hensyn til de lovede analyser af forårets fejlslagne forsøg i hoved-halskræft.
"Data vedrørende ofatumumab og zalutumumab præsenteres på ASCO
Resumé: Data fra adskillige studier præsenteres på ASCOs årsmøde 2010.
København, Danmark, 10. maj 2010 - Genmab A/S (OMX: GEN) offentliggjorde i dag,
at fire abstracts er blevet accepteret til præsentation på 2010 årsmødet i
American Society of Clinical Oncology (ASCO), som afholdes fra den 1.-8. juni i
Chicago, Illinois. Desuden er to andre abstracts blevet accepteret til
offentliggørelse.
Ofatumumab - Poster-session, 4. juni fra kl. 14 til 18 lokal tid.
Abstract #8042 Ofatumumab i kombination med CHOP hos tidligere ubehandlede
patienter med follikulært lymfom (FL).
Ofatumumab - Poster-session, 5. juni fra kl. 8 til 12 lokal tid.
Abstract #8095 Aktiviteten i ofatumumab (O), et nyt humant monoklonalt antistof
(mAb), der retter sig mod CD20, mod rituximab-følsomme cellelinier (RSCL),
rituximab-resistente cellelinier (RRCL), lymfom xenografter og primære
tumorceller, som stammer fra patienter med B-celle lymfom.
Ofatumumab - Poster-session, 7. juni fra kl. 14 til 18 lokal tid.
Abstract #6520 Kemoimmunterapi med ofatumumab, fludarabin og cyklofosfamid
(O-FC) hos tidligere ubehandlede patienter med kronisk lymfatisk leukæmi (CLL).
Ofatumumab - Kun online offentliggørelse
Abstract #e18525 Fase I undersøgelse i ofatumumab for japanske patienter med
recidiverende eller refraktær kronisk lymfatisk leukæmi (CLL) og småcellet
lymfatisk lymfom (SLL).
Zalutumumab - Kun online offentliggørelse
Abstract #e13102 ADCCs rolle i in vivo anti-tumor effekten af zalutumumab, et
humant anti-EGF receptor antistof.
De komplette abstracts vil være tilgængelige på www.asco.org den 20. maj 2010
kl. 18 lokal tid.
Genmab vil også præsentere det følgende, som er blevet accepteret til
præsentation under kate-gorien ?late breaking abstract?:
Zalutumumab - Mundtlig præsentation af abstract, 7. juni fra kl. 15 til 18 lokal
tid.
Abstract #LBA5506 Et ikke blindet, randomiseret, fase III studie med
zalutumumab, et humant monoklonalt EGF receptor antistof, mod bedste
understøttende behandling hos patienter med uhelbredelig pladecellecarcinom i
hoved og hals, der ikke har haft effekt af standard platinbaseret kemoterapi
(ZALUTE).
Det komplette abstract vil være tilgængeligt den 5. juni 2010 kl. 8 lokal tid.
Dette abstract vil også blive præsenteret på 2010 Best of ASCO San Francisco
mødet den 16.-17. juli 2010."
"Data vedrørende ofatumumab og zalutumumab præsenteres på ASCO
Resumé: Data fra adskillige studier præsenteres på ASCOs årsmøde 2010.
København, Danmark, 10. maj 2010 - Genmab A/S (OMX: GEN) offentliggjorde i dag,
at fire abstracts er blevet accepteret til præsentation på 2010 årsmødet i
American Society of Clinical Oncology (ASCO), som afholdes fra den 1.-8. juni i
Chicago, Illinois. Desuden er to andre abstracts blevet accepteret til
offentliggørelse.
Ofatumumab - Poster-session, 4. juni fra kl. 14 til 18 lokal tid.
Abstract #8042 Ofatumumab i kombination med CHOP hos tidligere ubehandlede
patienter med follikulært lymfom (FL).
Ofatumumab - Poster-session, 5. juni fra kl. 8 til 12 lokal tid.
Abstract #8095 Aktiviteten i ofatumumab (O), et nyt humant monoklonalt antistof
(mAb), der retter sig mod CD20, mod rituximab-følsomme cellelinier (RSCL),
rituximab-resistente cellelinier (RRCL), lymfom xenografter og primære
tumorceller, som stammer fra patienter med B-celle lymfom.
Ofatumumab - Poster-session, 7. juni fra kl. 14 til 18 lokal tid.
Abstract #6520 Kemoimmunterapi med ofatumumab, fludarabin og cyklofosfamid
(O-FC) hos tidligere ubehandlede patienter med kronisk lymfatisk leukæmi (CLL).
Ofatumumab - Kun online offentliggørelse
Abstract #e18525 Fase I undersøgelse i ofatumumab for japanske patienter med
recidiverende eller refraktær kronisk lymfatisk leukæmi (CLL) og småcellet
lymfatisk lymfom (SLL).
Zalutumumab - Kun online offentliggørelse
Abstract #e13102 ADCCs rolle i in vivo anti-tumor effekten af zalutumumab, et
humant anti-EGF receptor antistof.
De komplette abstracts vil være tilgængelige på www.asco.org den 20. maj 2010
kl. 18 lokal tid.
Genmab vil også præsentere det følgende, som er blevet accepteret til
præsentation under kate-gorien ?late breaking abstract?:
Zalutumumab - Mundtlig præsentation af abstract, 7. juni fra kl. 15 til 18 lokal
tid.
Abstract #LBA5506 Et ikke blindet, randomiseret, fase III studie med
zalutumumab, et humant monoklonalt EGF receptor antistof, mod bedste
understøttende behandling hos patienter med uhelbredelig pladecellecarcinom i
hoved og hals, der ikke har haft effekt af standard platinbaseret kemoterapi
(ZALUTE).
Det komplette abstract vil være tilgængeligt den 5. juni 2010 kl. 8 lokal tid.
Dette abstract vil også blive præsenteret på 2010 Best of ASCO San Francisco
mødet den 16.-17. juli 2010."
Nedenstående artikel giver i øvrigt lidt stof til eftertanke mht det mulige resultat af den filing, som Genmab hævder forstat at overveje.
Det omhandlede Erlotinib-studie viste ganske vist statistisk signifikans, hvilket jo ikke var tilfældet for Zalutumumab i det primære endpoint, survival. Når det ihukommes, at Zalutumumab gav en forbedret medianoverlevelse på 30% (6,7 mdr mod 5,2 for BSC-armen) og en forbedring i den progressionsfri overlevelse på 61%, ser resultaterne i Erlotinibforsøget dog ikke prangende ud: "29% reduction in risk of progression. Overall survival, a secondary end point, reached a median of 12 months with erlotinib and 11 months with placebo".
Netop dette var til syneladende også årsagen til, at advisory komitéen stemte mod at indstille Erlotinib til godkendelse
Når FDA alligevel godkendte Erlotinib skyldtes dette angiveligt medicineringen af placeboarmen samt en manglende "comparative effectiveness standard", hvilket vel ikke er helt uinteressant for så vidt som anvendelsen af anden medicinering i Zalutumumab-studiet jo blev oplyst at have været hyppigere forekommende i BSC-armen. Ligeledes kan man næppe sige at der forligger nogen effectiveness standard blandt de døende SCCHNpatienter, der har fejlet PCT-behandlingen.
"FDA Explains Erlotinib Approval After ODAC Advised Against It 12-1
Elsevier Global Medical News. 2010 Apr 21, E Mechcatie
Why did the Food and Drug Administration go against the advice of its own advisory panel to approve erlotinib tablets as a maintenance therapy for patients with locally advanced or metastatic non-small cell lung cancer?
Regulatory precedents, trial design, and lack of a comparative effectiveness standard all played a part in the unusual decision, according to Dr. Robert Justice, director of the Center for Drug Evaluation's Division of Oncology Drug Products.
The Oncologic Drugs Advisory Committee (ODAC) voted 12-1 against the FDA's giving a maintenance indication to erlotinib (Tarceva) at a meeting in December 2009. Members cited concerns about the modest effect in the study that manufacturer OSI Pharmaceuticals Inc. had submitted for approval, and the fact that only one study was available to support the new indication.
"After the December meeting there were extensive discussions within FDA regarding the application, and the ODAC's recommendation was carefully considered," Dr. Justice responded to an inquiry by this news organization following the approval announcement on April 19.
One issue was regulatory precedent, he said. The agency had approved bevacizumab (Avastin) in a regimen for nonsquamous non-small cell lung cancer (NSCLC) based on a 20% reduction in the risk of death, compared with chemotherapy alone. It had also accepted pemetrexed (Alimta) as a maintenance treatment for nonsquamous NSCLC "based on a 30% reduction in the risk of death compared to no maintenance therapy and a 21% reduction in the risk of death in patients with all types of NSCLC," noted Dr. Justice.
"The reduction in the risk of death with erlotinib maintenance treatment compared to no maintenance therapy was similar at 19%," he said.
The double-blind, international SATURN (Sequential Tarceva in Unresectable NSCLC) trial that formed the basis of the erlotinib application had randomized almost 900 patients with locally advanced or metastatic NSCLC that did not progress during first-line, platinum-based chemotherapy.
Median progression-free survival was 2.8 months in patients who were given erlotinib as maintenance therapy vs. 2.6 months in a placebo arm - a statistically significant difference that represented a 29% reduction in risk of progression. Overall survival, a secondary end point, reached a median of 12 months with erlotinib and 11 months with placebo - again, a statistically significant difference.
A second issue was trial design, Dr. Justice said. He cited general agreement "that the optimal trial design would have been erlotinib maintenance vs. erlotinib at progression of disease." Although OSI has agreed to do such a study as part of its postmarketing commitment, he suggested that "this may not reflect what will actually happen in practice."
In the SATURN trial, he noted, 259 patients (57%) of the placebo group received second-line treatments for NSCLC vs. 47% of the erlotinib group. Among those who received second-line treatments in the placebo group, 59% received an FDA-approved therapy: erlotinib or gefitinib (Iressa) at first progression in 14%, docetaxel (Taxotere) in 31%, and pemetrexed in 14%.
"Therefore the trial did test the value of maintenance therapy with erlotinib vs. treatment at progression with a second-line therapy in patients who chose to receive it and demonstrated a survival benefit," said Dr. Justice.
The absence of an FDA comparative effectiveness standard also played a role in the agency's decision, he added. "Once safety and effectiveness have been demonstrated, it is up to patients in consultation with their physicians to determine the treatment that is most appropriate for them," he said.
The new indication endorses erlotinib tablets for maintenance treatment of patients with locally advanced or metastatic NSCLC that has not progressed after four cycles of platinum-based, first-line chemotherapy. Erlotinib is also approved as a second-line treatment for locally advanced or metastatic NSCLC and, in combination with gemcitabine (Gemzar), as a first-line treatment of locally advanced, unresectable, or metastatic pancreatic cancer.
The approved dose of erlotinib, an epidermal growth factor receptor (EGFR) inhibitor, is 150 mg/day in NSCLC and 100 mg/day in pancreatic cancer. Rashlike events and diarrhea are the most common adverse events, experienced by more than 20% of NSCLC patients treated, according to the agency.
"We are delighted that lung cancer patients and their physicians will have the option of beginning Tarceva therapy in the first-line maintenance setting. We believe that Tarceva, as the only medicine approved in the maintenance setting" for the squamous and nonsquamous forms of NSCLC, "offers a valuable treatment option for these patients," said Colin Goddard, Ph.D., chief executive officer of OSI Pharmaceuticals in a statement on the company's Web site.
The company is committed, he added, to pursuing additional uses for erlotinib, "including as a first-line treatment for lung cancer patients with an activating EGFR mutation, as an adjuvant therapy in NSCLC, and in other tumor types such as ovarian cancer and hepatocellular carcinoma."
The European Medicines Agency announced on March 19 that it has issued a positive opinion on erlotinib as a maintenance treatment. The EMEA's positive opinion on extending the indication for erlotinib was expected to be endorsed by the European Commission within 45 days.
Jane Salodof MacNeil contributed to this report."
http://www.oncologystat.com/news/FDA_Explains_Erlotinib_Approval_After_ODAC_Advised_Against_It_12-1_US.html
Det omhandlede Erlotinib-studie viste ganske vist statistisk signifikans, hvilket jo ikke var tilfældet for Zalutumumab i det primære endpoint, survival. Når det ihukommes, at Zalutumumab gav en forbedret medianoverlevelse på 30% (6,7 mdr mod 5,2 for BSC-armen) og en forbedring i den progressionsfri overlevelse på 61%, ser resultaterne i Erlotinibforsøget dog ikke prangende ud: "29% reduction in risk of progression. Overall survival, a secondary end point, reached a median of 12 months with erlotinib and 11 months with placebo".
Netop dette var til syneladende også årsagen til, at advisory komitéen stemte mod at indstille Erlotinib til godkendelse
Når FDA alligevel godkendte Erlotinib skyldtes dette angiveligt medicineringen af placeboarmen samt en manglende "comparative effectiveness standard", hvilket vel ikke er helt uinteressant for så vidt som anvendelsen af anden medicinering i Zalutumumab-studiet jo blev oplyst at have været hyppigere forekommende i BSC-armen. Ligeledes kan man næppe sige at der forligger nogen effectiveness standard blandt de døende SCCHNpatienter, der har fejlet PCT-behandlingen.
"FDA Explains Erlotinib Approval After ODAC Advised Against It 12-1
Elsevier Global Medical News. 2010 Apr 21, E Mechcatie
Why did the Food and Drug Administration go against the advice of its own advisory panel to approve erlotinib tablets as a maintenance therapy for patients with locally advanced or metastatic non-small cell lung cancer?
Regulatory precedents, trial design, and lack of a comparative effectiveness standard all played a part in the unusual decision, according to Dr. Robert Justice, director of the Center for Drug Evaluation's Division of Oncology Drug Products.
The Oncologic Drugs Advisory Committee (ODAC) voted 12-1 against the FDA's giving a maintenance indication to erlotinib (Tarceva) at a meeting in December 2009. Members cited concerns about the modest effect in the study that manufacturer OSI Pharmaceuticals Inc. had submitted for approval, and the fact that only one study was available to support the new indication.
"After the December meeting there were extensive discussions within FDA regarding the application, and the ODAC's recommendation was carefully considered," Dr. Justice responded to an inquiry by this news organization following the approval announcement on April 19.
One issue was regulatory precedent, he said. The agency had approved bevacizumab (Avastin) in a regimen for nonsquamous non-small cell lung cancer (NSCLC) based on a 20% reduction in the risk of death, compared with chemotherapy alone. It had also accepted pemetrexed (Alimta) as a maintenance treatment for nonsquamous NSCLC "based on a 30% reduction in the risk of death compared to no maintenance therapy and a 21% reduction in the risk of death in patients with all types of NSCLC," noted Dr. Justice.
"The reduction in the risk of death with erlotinib maintenance treatment compared to no maintenance therapy was similar at 19%," he said.
The double-blind, international SATURN (Sequential Tarceva in Unresectable NSCLC) trial that formed the basis of the erlotinib application had randomized almost 900 patients with locally advanced or metastatic NSCLC that did not progress during first-line, platinum-based chemotherapy.
Median progression-free survival was 2.8 months in patients who were given erlotinib as maintenance therapy vs. 2.6 months in a placebo arm - a statistically significant difference that represented a 29% reduction in risk of progression. Overall survival, a secondary end point, reached a median of 12 months with erlotinib and 11 months with placebo - again, a statistically significant difference.
A second issue was trial design, Dr. Justice said. He cited general agreement "that the optimal trial design would have been erlotinib maintenance vs. erlotinib at progression of disease." Although OSI has agreed to do such a study as part of its postmarketing commitment, he suggested that "this may not reflect what will actually happen in practice."
In the SATURN trial, he noted, 259 patients (57%) of the placebo group received second-line treatments for NSCLC vs. 47% of the erlotinib group. Among those who received second-line treatments in the placebo group, 59% received an FDA-approved therapy: erlotinib or gefitinib (Iressa) at first progression in 14%, docetaxel (Taxotere) in 31%, and pemetrexed in 14%.
"Therefore the trial did test the value of maintenance therapy with erlotinib vs. treatment at progression with a second-line therapy in patients who chose to receive it and demonstrated a survival benefit," said Dr. Justice.
The absence of an FDA comparative effectiveness standard also played a role in the agency's decision, he added. "Once safety and effectiveness have been demonstrated, it is up to patients in consultation with their physicians to determine the treatment that is most appropriate for them," he said.
The new indication endorses erlotinib tablets for maintenance treatment of patients with locally advanced or metastatic NSCLC that has not progressed after four cycles of platinum-based, first-line chemotherapy. Erlotinib is also approved as a second-line treatment for locally advanced or metastatic NSCLC and, in combination with gemcitabine (Gemzar), as a first-line treatment of locally advanced, unresectable, or metastatic pancreatic cancer.
The approved dose of erlotinib, an epidermal growth factor receptor (EGFR) inhibitor, is 150 mg/day in NSCLC and 100 mg/day in pancreatic cancer. Rashlike events and diarrhea are the most common adverse events, experienced by more than 20% of NSCLC patients treated, according to the agency.
"We are delighted that lung cancer patients and their physicians will have the option of beginning Tarceva therapy in the first-line maintenance setting. We believe that Tarceva, as the only medicine approved in the maintenance setting" for the squamous and nonsquamous forms of NSCLC, "offers a valuable treatment option for these patients," said Colin Goddard, Ph.D., chief executive officer of OSI Pharmaceuticals in a statement on the company's Web site.
The company is committed, he added, to pursuing additional uses for erlotinib, "including as a first-line treatment for lung cancer patients with an activating EGFR mutation, as an adjuvant therapy in NSCLC, and in other tumor types such as ovarian cancer and hepatocellular carcinoma."
The European Medicines Agency announced on March 19 that it has issued a positive opinion on erlotinib as a maintenance treatment. The EMEA's positive opinion on extending the indication for erlotinib was expected to be endorsed by the European Commission within 45 days.
Jane Salodof MacNeil contributed to this report."
http://www.oncologystat.com/news/FDA_Explains_Erlotinib_Approval_After_ODAC_Advised_Against_It_12-1_US.html
10/5 2010 23:16 gentogen 0
29103 Tak for link. Super super interessant. På mange måder overraskende, at FDA helt konsekvent anlægger en positiv synsvinkel på alle diskussionspunkterne.
Det åbner jo også op for ganske meget at sige:
"Once safety and effectiveness have been demonstrated, it is up to patients in consultation with their physicians to determine the treatment that is most appropriate for them,".
Det er da lige til højrebenet. Så lad dog patienterne få muligheden for Zalu også...........
Det åbner jo også op for ganske meget at sige:
"Once safety and effectiveness have been demonstrated, it is up to patients in consultation with their physicians to determine the treatment that is most appropriate for them,".
Det er da lige til højrebenet. Så lad dog patienterne få muligheden for Zalu også...........
11/5 2010 08:15 Solsen 029110 Genmab har fået positive tilkendegivelse ved samtaler med opinionsdannere - kloge og indflydelsesrige folk bl.a. ODAC medlemmer.
De har ikke udmeldt hvad FDA har sagt eller om de har haft møder - forhåbentlig kan CC i forbindelse med regnskab måske afklare det spørgsmål.
Herefter kan partnerforhandlingerne åbnes - her må GSK komme i første alvorlige overvejelser om køb af hele butikken, hvis de ikke har været det før.
Jeg tror stadig, at Zalutumumab kan være bedre end Erbitux, der har alvorlige bivirkninger og 1-2% dødsfald der er infusionsrelateret.
De har ikke udmeldt hvad FDA har sagt eller om de har haft møder - forhåbentlig kan CC i forbindelse med regnskab måske afklare det spørgsmål.
Herefter kan partnerforhandlingerne åbnes - her må GSK komme i første alvorlige overvejelser om køb af hele butikken, hvis de ikke har været det før.
Jeg tror stadig, at Zalutumumab kan være bedre end Erbitux, der har alvorlige bivirkninger og 1-2% dødsfald der er infusionsrelateret.
12/5 2010 12:22 Stinker 029191 I dagens update på Genmab retter Danske også fokus mod Zalutumumab:
"Genmab (Buy) Genmab has maintained its outlook for 2010 while still excluding any full year guidance on royalties. The upcoming ASCO conference could restore some confidence in Zalutumumab and attract potential partners. However, the current focus is on the sale of the company?s manufacturing facility. We maintain our Buy recommendation and 12-month target price of DKK100 as we feel the current share price reflects far too large a discount of the pipeline."
"Genmab (Buy) Genmab has maintained its outlook for 2010 while still excluding any full year guidance on royalties. The upcoming ASCO conference could restore some confidence in Zalutumumab and attract potential partners. However, the current focus is on the sale of the company?s manufacturing facility. We maintain our Buy recommendation and 12-month target price of DKK100 as we feel the current share price reflects far too large a discount of the pipeline."
12/5 2010 12:47 collersteen 029192 NDA er også ude med en update idag - der er ikke sket det store og man fastholder buy med target 100.
Der er også hos NDA stor fokus på fabrikken og salget af denne. Man virker ret optimisk mht. at et salg gennemføres, men omtaler dog muligheden for at salgsprisen bliver noget lavere end hvad Genmab har meldt ud indtil videre.
Omkring Zalu har man ikke de store håb og det er også værdiansat til 0 i deres modeller.
"There was little news on the R&D side. The company states that there will
be an oral abstract session on zalutumumab at the American Society of
Clinical Oncology (ASCO) annual meeting in June. Genmab has not made
the final decision to cancel zalutumumab yet, but we believe it is unlikely
that zalutuumumab will make it to market."
Der er også hos NDA stor fokus på fabrikken og salget af denne. Man virker ret optimisk mht. at et salg gennemføres, men omtaler dog muligheden for at salgsprisen bliver noget lavere end hvad Genmab har meldt ud indtil videre.
Omkring Zalu har man ikke de store håb og det er også værdiansat til 0 i deres modeller.
"There was little news on the R&D side. The company states that there will
be an oral abstract session on zalutumumab at the American Society of
Clinical Oncology (ASCO) annual meeting in June. Genmab has not made
the final decision to cancel zalutumumab yet, but we believe it is unlikely
that zalutuumumab will make it to market."
