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Ny aftale for Genmab


57766 investor1989 4/6 2012 08:01
Oversigt

http://borsen.dk/nyheder/investor/artikel/1/234190/ge..

Genmab indgår endnu en aftale´.. Denne gang en aftale, med et betydeligt potentiale i fremtiden.
Jeg syntes det ser ud som om det går den rigtige vej for genmabs klinik for tiden.



4/6 2012 08:53 Sukkeralf 757769



Jeg synes det er en fremragende aftale af flere grunde.

Ved første øjekast kan upfront betalingen synes for lille, men her skal man altså stadig tænke på, at det ikke endnu er en gennemevalueret og valideret teknologi. Der går formentlig 2 år eller så, før vi ser et bispecifikt antistof lavet udfra Duobody teknologien i klinikken. Set i det lys er milestones pakken og royalties (formentlig omkring 5%) ganske flot.

Desuden betales alle omkostningen af Novartis, som nu er den anden helt store pharmaceutiske virksomhed der viser interesse for Doubody teknologien - det er jo en helt anden historie der er ved at udvikle sig, end det vi har set med eksempelvis Unibody teknologien, hvor man hidtil kun har kunnet tiltrække Lundbecks interesse.

Ergo er Doubody rimelig hot - og nu kan Genman stille og roligt med to store virksomheders ekspertise udvikle teknologien uden de store omkostninger. Det giver gode muligheder for milestones (måske royalties på langt sigte), gode muligheder for at tiltrække andre (og måske gode muligeheder for salg af Genmab) samt tillige at kvaliteten af deres egne bi-specifikke antistoffer løftes.

Desuden er milestones med til at holde en mulig Emission på afstand, hvilket jo i sig selv er ret positivt. Tror ikke der skal ret meget mere til, før der er tiltrækkelig med kapital til at vi får fase III data for Arzerra - og så kan man jo tage den derfra.

Så i mine øjne en perfekt aftale.

Herefter venter der tillige gode data fra Daratumumab i aften - og man må forvente at de er gode, da Genmab allerede bruger data i forhandlinger med eventuelle partnere (den helt store trigger i 2012), at data indtil videre har været gode og man med de nye data er begyndt at tale om mono-terapi samt det faktum, at data præsenteres mundtligt på ASCO.

Mvh
Sukkeralf



4/6 2012 09:01 investor1989 457770



Er også helt enig i at Denne aftale, og faktisk også den vi så i sidste uge er et tegn på at genmab har gang i klinikken. Jeg ved ikke hvorfor, men sidder med en følelse at der er en 100+$ upfront i Daradealen :)

mht. fabrikken er jeg snart af den opfattelse at Genmab bare kan give den væk gratis. Så sparer de 40-50 millioner om året det koster at holde den kørende. Og ydermere fjerner det den usikkerhed der er over aktien.
Og sidst men ikke mindst er fabrikken det sidste symbol på "det gamle genmab". Det genmab jeg mener man idag har taget endnu et skridt væk fra.

Og ja ved godt jeg overdriver når jeg siger give fabrikken væk, men bare skyde den af for en slik.



4/6 2012 09:12 Sukkeralf 257774



Humax IL8 aftalen kommer aldrig til at betyde noget - den minder sikkert om HumaxCD4 aftalen og mit gæt er at også Zalutumumab på et eller andet tidspunkt ender i sådan en aftale - her måske lige en tand bedre.

Gætter også på at Genmab skiller sig af med fabrikken senest i H1 2013 uanset prisen, så det ligesom er et sluttet kapitel.

Mvh
Sukkeralf



4/6 2012 14:00 investor1989 057794



Kommer der Daratumumab data efter luk idag ?



4/6 2012 14:29 gentogen 157796



Updated safety and preliminary efficacy data from the study will be presented in an oral session at the 2012 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago at 10:30AM Central time (CT) on June 4. Abstracts have been published at the ASCO website at www.asco.org/abstracts.

An oral presentation of the daratumumab study data will also be given at the 17th Congress of the European Hematology Association (EHA) in Amsterdam. Abstracts will be published online on May 21 at the EHA website at www.ehaweb.org.

Following the oral presentations, selected slides showing the daratumumab data will be available on Genmab's website at www.genmab.com/events.



4/6 2012 14:40 investor1989 057797



Det er 17.30 så vidt jeg kan se ?



5/6 2012 06:45 w 057847



Var Novartis så det hemmelige top 10 pharma selskab, som Genmab tidligere talte om?

sent from iPhone



5/6 2012 06:45 w 057848



Var Novartis så det hemmelige top 10 pharma selskab, som Genmab tidligere talte om?

sent from iPhone



5/6 2012 08:37 investor1989 057856



Nej. Genmab skriver i denne meddelelse at den anden aftale er med en anden stor pharma partner.



5/6 2012 12:49 w 057870



Skal det ikke forståes at den første var Lundbeck?

sent from iPhone



5/6 2012 12:53 akademikeren 057871



nej den til lundbeck var på unibody. Der er 2 partnere på Duobody technologien og den første er stadigvæk mystery!



5/6 2012 12:56 w 057872






4/6 2012 18:01 investor1989 057829



Er der kommet noget fornuftigt ud ?



4/6 2012 20:56 akademikeren 257844



• Daratumumab has shown a favorable safety profile as monotherapy in relapsed and relapsed/refractory MM patients
• MTD has not yet been established/reached
• In 18 of 29 heavily pretreated MM patients receiving 8 weeks of daratumumab as monotherapy in doses up to 16mg/kg, a marked reduction in M-component has been observed, corresponding to preliminary responses of:
- 7 pts achieving PR - 4 pts achieving MR - 7 pts achieving SD
• Biochemical responses were accompanied by clearance of myeloma cells from the bone marrow
• Dose escalation is ongoing and will be followed by a 24 week study (Part 2) to evaluate long-term safety and efficacy
• Continuous therapy studies and combination strategies planned (e.g. with bortezomib plus dex; lenalidomide plus dex)



4/6 2012 21:14 prebenjensen 057845



Mon det er nu rakettens 1. trin affyres.



4/6 2012 21:43 investor1989 057846



Er der nogle der kan kommentere på det?
Er ikke særlig god indenfor MM, så ved ikke rigtig hvad jeg skal holde resultaterne op imod.



5/6 2012 07:10 celsius 057850



Svar til W vedr. hemmelig partner:

"Vi er utroligt glade for at indgå Genmabs andet samarbejde vedrørende DuoBody"

bortset fra det så er det en fantastisk fremtid vi Genmab aktionær kan se frem til ,, denne her gang kan det ikke gå galt,, i morgen onsdag tror jeg vi runder kurs 50,,



5/6 2012 08:05 JKY_VH 057853



Ja, lad os endelig håbe det.



5/6 2012 08:09 Solsen 357854



Jeg vil blive overrasket, hvis vi når 50 i morgen.

Data bekræftede, at Daratumumab har en fremtid. Men de nye data skabte ikke lys over den rette dosering og heller ikke MTD (max tolerede dosis).

Sidstnævnte er godt nok, da safety synes ok og ikke dosisafhængig - hviket de viste data dog ikke bekræfter.

På de offentliggjorte slides synes det som om, at forsøget udvides med flere pts i diverse dosisgrupper - flere steder står der (3) yderligere patienter.

Hvis jeg læser det rigtigt kan det betyde, at en licensaftale måske ligger lidt længere fremme end jeg tidligere har antaget, idet der er flere pts undervejs for at kunne fastslå dosis i det videre forsøg - vel også derfor vi ikke har fået gang i kombiforsøgene endnu trods længe lovet (soon).



5/6 2012 09:23 Sukkeralf 357860



Hej Solsen

Her er jeg ikke helt enig.

1) Som du skriver så viser data, at der er muligheder med daratumumab - det er vel alt hvad en partner behøver vide på nuværende tidspunkt. Det kan ikke betyde alverden hvad den præcise dosis skal være, men et eller andet sted er det jo rent gætværk hvornår sådan en aftale kommer. Der er så mange øvrige ting der spiller ind, så det kan vi nok ikke komme med helt gode begrundelser for alligevel.

Jan har tidligere nævnt at protokollerne til kombinationsstudierne hos EMA var klar og endda synlige (har ikke lige fundet dem), så mon ikke man har lagt sig fast på en dosis eller måske flere eller med muligheden for at øge den undervejs, hvis det skulle være muligt.

Man skal vel mest af alt ligge sig fast på laveste dosis man vil starte med - og her kunne 2-4 mg jo være et godt bud som start.

Har ikke gravet så meget i det, da jeg ikke lige har tid - vil forsøge at kigge lidt på det sent i aften.

Det er i det hele taget lidt svært at finde data på antistoffer som mono-terapi. Har du nogle gode eksempler til sammenligning.

Umiddelbart synes jeg responsraten ser meget fornuftig ud, når du kommer op i en dosisstørrelse, som man må forvente de vil anvendes - det kunne have været flot hvis der havde været en enkelt CR eller uCR eller bare VGPR !

Nå smutter videre...........



5/6 2012 09:26 gentogen 257861



Jeg er meget langt fra ekspert, men jeg tror, du udlægger metoden forkert. Som jeg læser det, er de meget tæt på MTD, da de netop er begyndt på max anslået dosis.Dog vil der ofte være ret stor statistisk usikkerhed om MTD i fase I alligevel. Men ja. De er ikke så langt fremme, som vi kunne ønske, men til gengæld ser det meget fornuftigt ud. Der er jo meget tydelig klinisk effekt.

Om metoden:
The traditional 3+3 design remains the prevailing method for conducting phase I cancer clinical trials (7). It requires no modeling of the dose-toxicity curve beyond the classical assumption for cytotoxic drugs that toxicity increases with dose. This rule-based design proceeds with cohorts of three patients; the first cohort is treated at a starting dose that is considered to be safe based on extrapolation from animal toxicological data, and the subsequent cohorts are treated at increasing dose levels that have been fixed in advance (Figure 2, B). Historically, dose escalation has followed a modified Fibonacci sequence in which the dose increments become smaller as the dose increases (eg, the dose first increases by 100% of the preceding dose, and thereafter by 67%, 50%, 40%, and 30%-35% of the preceding doses). In most cases, the prespecified dose levels do not fit the exact Fibonacci sequence as described in the 12th century (5). If none of the three patients in a cohort experiences a dose-limiting toxicity, another three patients will be treated at the next higher dose level. However, if one of the first three patients experiences a dose-limiting toxicity, three more patients will be treated at the same dose level. The dose escalation continues until at least two patients among a cohort of three to six patients experience dose-limiting toxicities (ie, ≥33% of patients with a dose-limiting toxicity at that dose level). The recommended dose for phase II trials is conventionally defined as the dose level just below this toxic dose level.



5/6 2012 09:45 Solsen 357863



Tak til både Sukkeralf og Gentogen.

Ja I kan have ret i jeres synspunkter og til Gentogen så jeg jeg ikke uenig blot synes jeg det pågældende slide er svær at tolke.

Havde der været ord på kunne jeg måske have forstået det bedre - men det må vi jo spørge til.

Vi kan ikke se af data om sideeffects stiger med dosis, hvilket er en meget vigtig oplysning, når vi skal vurdere dosis - jeg synes der er en del spørgsmål endnu.

Men et gæt på 30-50% ORR der materialiseres i større forsøg er fuldt tilfredstillende for os aktionærer og mere end Winkel har stillet os i forventning !

Et monotrial imod approval kan blive offentliggjort - det er trods alt heavy treated patienter vi har i nærværende forsøg så hatten af for Daratumumab !!!



5/6 2012 10:25 gentogen 157865



Det er vist kun specialister, der for alvor kan vurdere de fremlagte tal. Reglerne for PR, CR etc. er også meget detaljerede og komplicerede. Der kræves sammanfald af forskellige målinger, som ikke i alle tilfælde er tilgængelige. Denne patientgruppes alternativer er få og ikke overbevisende, så jeg tilslutter mig Solsens afsluttende vinken med hatten ...

Se for eksempel:

http://myeloma.org/pdfs/IMWG_guidelines_ineligible.pdf



5/6 2012 10:38 akademikeren 157866



Hej,

I refractory settings er den enøjede konge. Men det er en gruppe som er svære at behandle.

Jeg fandt følgende treatment options:

Treatment for myeloma that comes back

Your doctor may call this relapsed myeloma. If your myeloma returns your doctor may suggest treatment with the biological therapy bortezomib (Velcade). If bortezomib is not suitable for you, your doctor may suggest another treatment. This may be a different combination of chemotherapy drugs with or without a biological treatment such as thalidomide or lenalidomide (Revlimid). Some people may have lenalidomide with the steroid drug dexamethasone.

Tjek bivirkninger for Velcade her:

http://cancerhelp.cancerresearchuk.org/about-cancer/t..

Velcade er et Johnson & Johnson stof.



5/6 2012 12:13 Solsen 057868



Hvad er fakta

29 behandlet med Daratumumab:
- heraf 11



5/6 2012 12:16 Solsen 057869



Så havde man skrevet et langt indlæg der ender med næsten igenting

Må vente til jeg får bedre tid .... men denne skal I have, nu når aka skriver om velcades sideeffects....

Revlimids sideeffects http://www.fda.gov/Safety/MedWatch/SafetyInformation/..



5/6 2012 14:05 ajpi 057878



@Solsen: Vi beklager at dit indlæg gik galt, og vi har selvfølgelig fremtidigt fikset den fejl der var skylden (fejlen fra vores side var at et "<" efterfulgt af et bogstav ignorerede resten af indlægget).



5/6 2012 15:33 Sukkeralf 057885



Lige et kort indspark - et er også hvad max dosis er som monoterapi, men det kan jo ændre sig, når man behandler i kombination med de valgte lægemidler - derfor er det måske ikke unaturligt, at man også i kombinationsstudierne evt. vil køre med forskellige doser af daratumumab.

Behandlingerne med både Velcade og Revlimid er jo velkendte og dosis ligeså.

Nå men vi må grave mere i sagerne.

Kunne være cool med en række spørgsmål til Genmab.

Ellers kommer der jo to præsentationer her i juni - den første hos J. er allerede i morgen og man kan efterfølgende lytte til webcastet.

....på vej tilbage i malerbøtten



5/6 2012 20:33 Solsen 057903



De skulle have oplyst på ASCO, at 4-8 mg giver fuld dækning af receptorerne og at 24 mg blot afprøves for at få bedre indblik i safety.

Usædvanligt at pts evt. tåler 3-6X dosis med fuld effekt !



5/6 2012 23:01 Sukkeralf 057915



Hvis ikke vi bliver klogere efter de kommende prøsentationer, så er der måske en mulighed om et par uger:

Daratumumab Data Presented at ASCO

Preliminary data from the Phase I/II study of daratumumab in multiple myeloma was presented today at the 2012 American Society of Clinical Oncology (ASCO) Annual Meeting. Click here to view an abridged version slide presentation for investors. Study investigator Dr. Torben Plesner was also interviewed by the International Myeloma Foundation (IMF) following the presentation. A link to the interview will be available at the IMF website in the coming weeks.

Dette interview med TP kunne være interessant.

Mvh
Sukkeralf



5/6 2012 23:54 gentogen 057917



Launched in 2001, the International Myeloma Working Group (IMWG)-the research arm of the International Myeloma Foundation-has had many successes that have changed the landscape of myeloma research. Through the collaboration of its members - 159 of the top myeloma researchers in the world-the IMWG has revolutionized the way myeloma is diagnosed, treated, and managed.

But they don't always agree...

On June 13th, the IMWG Conference Series will kick off with a live webcast of a debate between world-recognized experts from the United States and Europe. You won't want to miss this event, as four of our top myeloma researchers, Drs. Durie, Richardson, Palumbo and San Miguel, take on the first topic of the series: Making Sense of Treatment.

For the first time ever, the IMWG Conference will be webcast live and open to the public. Registration is free. Please click here to view the event details and get your ringside seats to this groundbreaking event!

This is one conference you won't want to miss! Register today.

Live streamed from the Sofitel Legend Hotel
Oudezijds Voorburgwal 197
NL-1012 - EX Amsterdam



6/6 2012 00:12 Sukkeralf 057918



Spændende gentogen !

Indtil videre har jeg ikke fundet andre antistoffer som i monotherapi virker mærkbart bedre end Daratumumab - indtil flere endda med meget lille virkning, men det er svært helt at få et overblik, da mange af resulaterne ligeledes er indledende data.

Kunne være rart med et review fra 2011/2012 !

Mvh
Sukkeralf



6/6 2012 11:46 Sukkeralf 157941



Her er protokolleren for kombinationsstudierne hos EMA. Der indrulles henholdsvis 40 og 50 patienter i hvert studie worldwide.

Det er dose-eskaleringsstudie med fokus på safety.

Mon ikke det er tæt på med hensyn til første indrullede patient.

Med Bortezomib + Dexamethasone:

https://www.clinicaltrialsregister.eu/ctr-search/tria..

Med Lenalidomide + Dexamethasone:

https://www.clinicaltrialsregister.eu/ctr-search/tria..



6/6 2012 16:02 gentogen 057974



Register for Free Teleconference: Myeloma Updates 2012
Brian G.M. Durie, MD, summarizes highlights of ASCO/ EHA/ IMWG Summit for patients, family members, caregivers and healthcare professionals.
Thur, June 28, 2012

http://myeloma.org/ArticlePage.action?tabId=0&men..



6/6 2012 22:58 Sukkeralf 258006



En ganske fin præsentation hos Jefferies:

http://wsw.com/webcast/jeff68/register.aspx?conf=jeff..

Jan nævner faktisk at en af patienterne daratumumab studiet behandlet med 8mg/kg har et uCR, så det er dejligt

Desuden står der på en af de sidste slides, at der indsendes en IND her i midten af 2012, så snart en ny klinisk kandidat - det viste jeg ikke

Desuden en række andre gode ting, så den er bestemt værd at lytte til.

Igen kan jeg kun understrege, at jeg ikke fatter at Genmabs kurs ikke får bare lidt medgang i disse dage. Med de seneste nyheder og Jans optimisme i denne præsentation burde vi være omkring kurs 50.

USA endte i pænt plus, så hvis futterne ikke ser alt for røde ud må Genmab få et løft i morgen. Nogen må vågne op - kom snart med opdaterede kursmål, hvis eller nogen følger denne Aktie.

Ellers lukker jeg øjnene indtil en Dara-deal er en realitet.

Lidt desperat efter lidt medgang må man da have lov at være sådan en halv-sen aftentime

Mvh
Sukkeralf



7/6 2012 09:57 celsius 058015



Tak Sukker for dit dejlige indlæg,, men hvad betyder det når du skriver 33% PR i Dara og hvad er et uCR og hvad betyder det når du skriver en IND blir indsendt i midten af 2012 så forklar venligst hvad PR - uCR - IND står for -:)



7/6 2012 11:04 Sukkeralf 158016



Hej Celsius

Det studie der kører med Daratumumab er dosis-ekskaleringsstudie med fokus på sikkerhed og finde MTD (Max Tolererede dosis).

De sekundære endpoints er også at kigge lidt på effekten.

Når man ser på de 9 patienter der er behandlet med henholdsvis 4mg/kg og 8 mg/kg samt 16 mg/kg (3 patienter ved hver dosis), så respondere 6 ud af de 9 patienter på behandlingen (de tre har Partiel Response (PR), mens de sidste tre har MPR (minor Partiel Response) og de sidste tre har SD (Stable Disease).

Jan sagde så på præsentationen, at det ene PR nok nærmere er et uCR, altså unconfirmed Complete Response - canceren er formentlig helt væk !

IND bestyder Investigational New Drug - og er den ansøgning man sender til sundhedsmyndighederne for, at få lov at starte det frøste kliniske studie op. Altså at teste sit lægemiddel for første gang i mennesker.

Håber det giver mere mening

Mvh
Sukkeralf



7/6 2012 11:53 gentogen 058017



Daratumumab

Daratumumab is being developed by the Danish pharmaceutical company Genmab. It is a monoclonal antibody that binds to the CD38 molecule, which is found on the surface of multiple myeloma cells. Daratumumab then signals for the immune system to kill the myeloma cells.

Dr Torben Plesner from Vejle Hospital in Vejle, Denmark, presented preliminary efficacy results from a Phase 1/2 study of daratumumab in relapsed and refractory myeloma patients (abstract).

Twenty-nine patients included in the study received varying doses of daratumumab up to 16 mg/kg, along with occasional doses of dexamethasone.

To participate in the trial, patients had to have at least two previous lines of therapy, and most patients had considerably more than that. All patients previously received treatment with Velcade and either Revlimid or thalidomide.

Treatment with daratumumab achieved a partial response in 24 percent of the patients, a minimal response in 14 percent of the patients, and stable disease in another 24 percent of the trial participants.

According to the researchers, the drug's side effects at these doses are manageable. Specifically, 14 percent of patients experienced serious side effects, including low red blood cell and platelet counts, abnormal liver function tests, spasms of the airways making breathing difficult, and an inflammatory syndrome.

Dr. Plesner said that additional studies with myeloma patients are planned that will look at continuous daratumumab therapy and also daratumumab in combination with Revlimid or Velcade plus dexamethasone.

For further details, see the slide deck (PDF) for Dr. Plesner's presentation, which he has made available as a courtesy to The Beacon's readers.

In his discussion of the daratumumab results, Dr. Jakubowiak described the drug as "very active" with no significant toxicity issues. He also noted that the results may be even more promising than they seem at first glance. In Dr. Plesner's trial, the drug showed greater efficacy at its higher doses, and there seems to be scope to increase the dose beyond what has been tested in the trial so far.

Myeloma presentations from later today, Day 4, of the ASCO 2012 meeting also will be summarized in ASCO daily updates to be published later today or tomorrow. Additional coverage of key research results from the meeting will continue throughout the rest of the week in individual, topic-specific news articles.

For all Beacon articles related to this year's ASCO meeting, see The Beacon's full ASCO 2012 coverage.



7/6 2012 11:58 gentogen 058018



Today is the fourth day of the American Society of Clinical Oncology (ASCO) 2012 annual meeting, and the meeting continued to be filled with interesting results from clinical trials in multiple myeloma patients.

The day included a session of oral presentations in the late morning that featured results from three clinical trials involving immunotherapy agents.

The three compounds, elotuzumab, siltuximab, and daratumumab, belong to the class of drugs called monoclonal antibodies. They work by identifying proteins on the surface of myeloma cells and signal for the immune system to destroy the cancer cells. All three drugs are administered via infusion, rather than as a tablet or capsule.

The results presented during the session can be considered good news for myeloma patients. Two of the three drugs showed promising results in terms of both efficacy and tolerability, and one of those drugs - elotuzumab - is already in late stage clinical trials.

Elotuzumab

Elotuzumab, which is being developed by Bristol-Myers Squibb (NYSE: BMY), is the monoclonal antibody that is furthest along in clinical development for multiple myeloma.

During the session this morning, Dr. Philippe Moreau from the University Hospital in Nantes, France, presented updated results from a Phase 2 study of elotuzumab in combination with Revlimid (lenalidomide) and low-dose dexamethasone (Decadron) in patients with relapsed and refractory multiple myeloma (abstract).

The study included 73 patients. All patients were required to have had one to three previous lines of therapy. Patients previously treated with Revlimid could not participate in the trial.

Half of the patients received 10 mg/kg elotuzumab, while the other half received 20 mg/kg.

Preliminary results of the study presented at the American Society of Hematology's annual meeting in December had already indicated that the lower dose seems to be more effective than the higher dose (see related Beacon news).

The results Dr. Moreau presented today confirmed that trend.

Overall, 92 percent of patients in the 10 mg/kg group and 76 percent in the 20 mg/kg group responded to treatment. Among patients with just a single previous line of therapy, 91 percent had a partial response or better. Median progression-free survival across all the patients in the trial has not yet been reached after a median follow-up time of 17.2 months.

Serious side effects occurred in a limited number of patients and consisted primarily of low white blood cell counts and low platelet counts. There were, however, four cases of second cancer among the trial participants.

In his review of the three presentations given during this session, Dr. Andrzej Jakubowiak from the University of Chicago said that the elotuzumab combination demonstrates "very promising" efficacy and very good tolerability. Phase 3 trials of the drug in combination with Revlimid are already ongoing in both newly diagnosed and relapsed and refractory myeloma patients.

Siltuximab

Siltuximab is being developed by Janssen Biotech, a Johnson & Johnson company (NYSE: JNJ). The antibody blocks the activity of IL-6, a protein that facilitates myeloma cell growth and resistance to dexamethasone.

Dr. Robert Orlowski from the MD Anderson Cancer Center in Houston presented results from a Phase 2 study comparing siltuximab plus Velcade (bortezomib) to Velcade alone (abstract).

The study included 286 multiple myeloma patients with one to three previous lines of therapy. Patients were not permitted to have been previously treated with Velcade.

Results showed that more patients on siltuximab plus Velcade responded to treatment (55 percent) than patients on Velcade alone (47 percent).

The median progression-free survival time was longer for patients receiving siltuximab plus Velcade (8.1 months), compared to patients receiving Velcade alone (7.6 months).

However, the median overall survival time was longer for patients receiving Velcade alone (36.9 months) compared to those receiving siltuximab plus Velcade (30.8 months).

More patients receiving siltuximab plus Velcade experienced severe or life-threatening side effects (91 percent) than patients receiving Velcade alone (74 percent).

Although the results of this trial were not what he and his colleagues initially expected, Dr. Orlowski noted that other trials investigating siltuximab as a potential treatment for myeloma are still ongoing or planned.

Dr. Orlowski has made his presentation available for download and viewing as a courtesy to The Beacon's readers.



7/6 2012 12:05 Sukkeralf 158020



Synes nu ikke siltuximab resultaterne er specielt opløftended overhovedet !

Det tegner da godt for Genmab.

Elotuzumab viste stort set igen effekt som monoterapi, så mon ikke Daratumumab er disse overlegen.

Mvh
Sukkeralf



7/6 2012 12:00 Sukkeralf 058019



Tak gentogen - du støver gode ting op

Det er nemlig ret vigtigt, når man kigger på effekten kun at tage de doser man forventeligt vil anvende fremover. I de slides Genmab har lagt frem på hjemmesiden medtager de her kun 4, 8 og 16 mg/kg.

Mvh
Sukkeralf



7/6 2012 15:42 gentogen 058030



Et par nye studier med Ofatumumab:

Study of OFATUMUMAB as Part of the Scheme of Reduced Intensity Conditioning in High Risk Non-Hodgkin Lymphoma B Patients
This study is currently recruiting participants.
Verified June 2012 by Grupo Español de Linfomas y Transplante Autólogo de Médula Ósea


First Received on June 5, 2012.

OG

Treatment With Bendamustine, Ofatumumab and MethylPrednisolone in Relapsed B-CLL (BOMP)
This study is not yet open for participant recruitment.
Verified June 2012 by Groupe Ouest Est d'Etude des Leucémies et Autres Maladies du Sang GOELAMS


First Received on May 30, 2012



8/6 2012 08:35 Solsen 058050



Det ser lovende ud - kunne være rigtig godt med nogle CR - helt uhørt hvis det skulle ske hos disse patienter.

Mon ikke Genmab arbejder på en SPA med FDA med Daratumumab og derefter partnerskab.

Det øger i hvert tilfæde værdien på Daratumumab.

Winkel har fået lidt spotlight ...http://finance.yahoo.com/news/genmab-ring-nasdaq-stoc..



8/6 2012 08:51 gentogen 058052



Ellers er begejstringen til at overse;
Although the annual meeting of the American Society of Clinical Oncology (ASCO)-which ended Tuesday in Chicago-does not have the number or scope of abstracts presented at the meetings of the American Society of Hematology (ASH), there were nonetheless several important presentations of interest to members of the myeloma community.

Three presentations in the frontline setting demonstrated the remarkable benefits with Carfilzomib combinations:

?Abstract 8009 from the French IFM group summarized results with carfilzomib plus melphalan and prednisone (CMP), which can be compared with the extensive prior data with Velcade (V) MP (VMP). The objective response rate (ORR) (>50% regression) with CMP was an impressive 92% (versus 71% with VMP), with 42% having > a very good partial response rate (VGPR) with CMP.


?Abstract 8010 from the Mayo Clinic group in Scottsdale, Ariz., looked at a new regimen called CYCLONE, incorporating carfilzomib, cyclophosphamide, thalidomide and dexamethasone. At the early phase of this study all patients had responded, with 83% achievingVGPR, with a combination that appeared to be reasonably well tolerated.


?Abstract 8011, from Dr. Andrzej Jakubowiak of the University of Chicago Medical Center, and colleagues, provided follow-up data utilizing his frontline combination of carfilzomib and lenalidomide (Revlimid) plus dexamethasone. Emphasis was placed upon the fact that 42% of patients achieved stringent CR. Progression-free survival (PFS) was 97% at 12 months and 92% at 24 months, indicating ongoing treatment benefit. In contrast, the Mayo Clinic team from Rochester, Minn. (Abstract 8096), detailed the longer-term outcomes with the two-drug combination of lenalidomide (Revlimid) plus dexamethasone as first therapy. Tracking 286 consecutive patients, the median survival was 8 years, reflecting both induction and follow-up therapy.
Clearly, it will take some time to assess which is the ideal combination to achieve both excellent early results, acceptable toxicity, and the best longer-term benefit.

In the relapse/refractory setting many single agents and combinations were evaluated. Of the single agents, both pomalidomide and carfilzomib demonstrated expected efficacy, with ORRs of about 30% or better. It is hoped that both will be approved by the FDA soon (watch for this news in upcoming issues of the Myeloma Minute).

Of the newer agents, both elotuzumab and MLN 9708 (an oral proteasome inhibitor) continued to show promising results.

Among agents at an early stage of development, results were rather disappointing. Obatolclax (anti-BCL-2; Abstract 8013); siltuximab (anti-IL-6; Abstract 8018); and daratumumab (anti-IL-6; Abstract 8018) showed limited evidence of efficacy.

In other abstracts, a retrospective analysis of 841 consecutive patients from the City of Hope (Abstract 8038) showed that the primary correlates for development of second primary malignancies (SPMs) were older age (> age 55 years) and non-Hispanic white race (P=0.01). There were several interesting abstracts that will undoubtedly give rise to further research. Among them, Abstract 8040 suggested that t(11;14), commonly thought to be a "good-risk" translocation, may have a negative impact related to ASCT; Abstract 8097 presented results of a large analysis demonstrating a different pattern of disease and outcomes in Asian patients and Abstract 8088 presented inconsistencies in systems used to assess risk progression in smoldering myeloma



8/6 2012 09:15 Sukkeralf 058053



Angående Daratumumab så hænger kommentaren i dit seneste indlæg ikke sammen med hvad der tidligere er sagt, fra en af selvsamme personer:

"In his discussion of the daratumumab results, Dr. Jakubowiak described the drug as "very active" with no significant toxicity issues. He also noted that the results may be even more promising than they seem at first glance. In Dr. Plesner's trial, the drug showed greater efficacy at its higher doses, and there seems to be scope to increase the dose beyond what has been tested in the trial so far".

Desuden angiver de target forkert i parantesen, så måske en lille fejl.

Det virker en anelse fokuseret på Carfilzomib !!

Mvh
Sukkeralf



8/6 2012 09:42 gentogen 058054



Tak for bemærkningen. Jeg tillægger det sådan set heller ikke den store betydning. Da gennemgangen jo sammenblander alle mulige slags behandlinger, er jeg også lidt tilbøjelig til at se den meget korte kommentar om Dara som en slags fejl. Ikke desto mindre er det bare lidt interessant at se, hvordan det omtales pt., mens vi venter på interviewet med Torben Plesner.



8/6 2012 10:06 Sukkeralf 058056



Enig - er også super glad for disse indlæg du kommer med.

En kildeangivelse eller link ville være dejligt

Mvh
Sukkeralf



9/6 2012 13:25 Sukkeralf 158097



Lidt mere fra the Beacon:


Interim results of an ongoing early-stage clinical trial indicate that daratumumab is safe as a treatment for relapsed and refractory multiple myeloma. In addition, daratumumab showed promising activity in the trial participants.

Dr. Torben Plesner of Vejle Hospital in Denmark presented the preliminary results of the Phase 1/2 study at the 48th annual meeting of the American Society of Clinical Oncology (ASCO) on Monday.

"The efficacy [of daratumumab] looks very promising," said Dr. Andrzej Jakubowiak, the director of the myeloma program at the University of Chicago, who was not involved in the study.

Dr. Leif Bergsagel from the Mayo Clinic in Arizona, who also was not involved in the study, agreed with Dr. Jakubowiak's assessment of daratumumab.

"It appears to be the most promising monoclonal antibody for multiple myeloma to date and one of the most promising truly novel agents for multiple myeloma. It appears to have low toxicity and ought to combine well with other regimens," said Dr. Bergsagel.

Dr. Plesner and his colleagues will evaluate the long-term safety and efficacy of daratumumab in the Phase 2 part of the trial. He added that additional studies with myeloma patients are planned that will look at continuous daratumumab therapy as well as daratumumab in combination with Revlimid (lenalidomide) or Velcade (bortezomib) plus dexamethasone (Decadron).

"What we have observed from treatment with daratumumab as a single agent for a short period of time may be improved by prolonged treatment with the antibody and combinations with other anti-myeloma drugs," said Dr. Plesner.

Daratumumab is being developed by the Danish pharmaceutical company Genmab. It belongs to the same class of drugs - called monoclonal antibodies - as elotuzumab and siltuximab. Specifically, daratumumab binds a protein called CD38, which is found on the surface of multiple myeloma cells. It then signals for the immune system to kill the myeloma cells.

In the current Phase 1 part of the study, researchers sought to investigate the safety profile of daratumumab and to determine the maximum tolerated dose of the drug in relapsed or refractory myeloma patients.

To date, the study has enrolled 29 relapsed or refractory myeloma patients.

All patients had relapsed after receiving at least five prior lines of therapy, including Velcade, Revlimid, and thalidomide (Thalomid); 67 percent of patients had also received a stem cell transplant before entering the study.

Patients received varying doses of daratumumab ranging from 0.005 mg/kg up to 16 mg/kg for eight weeks.

After some patients developed infusion-related reactions, dexamethasone was added to the treatment regimen.

According to Dr. Plesner, patients received a total of 200 mg of dexamethasone over an eight-week period, which is equivalent to 25 mg of dexamethasone per week per patient. Dr. Plesner explained that this dose is less than what is referred to as "low-dose" dexamethasone (40 mg per week).

At the most recent follow-up, researchers found that 24 percent of patients have achieved a partial response. An additional 14 percent of patients have achieved a minimal response, and 24 percent of patients have stable disease.

"Since the patients enrolled in the trial have been heavily pretreated, we do not think that the responses observed are caused by dexamethasone," said Dr. Plesner.

Dr. Bergsagel agreed with Dr. Plesner's assessment of the response rates. "I would expect most of the patients entered in this study would have had a lot of dexamethasone in their previous regimens, and I think it unlikely they would have much of a response to dexamethasone alone at this point," he explained.

Of the patients who received 1 mg/kg or below of daratumumab, 47 percent experienced a reduction in their blood or urine monoclonal protein levels.

Monoclonal proteins are produced by abnormal plasma cells and are often measured in blood and urine tests to track the progress of multiple myeloma. Reductions in monoclonal protein levels typically signify a decrease in the number of active myeloma cells in the body.

Of the three patients who received 2 mg/kg of daratumumab, one patient experienced a 67 percent reduction of monoclonal proteins in the blood and a 55 percent reduction of monoclonal proteins in the urine.

Dr. Plesner pointed out that starting at 4 mg/kg, more systematic responses to treatment could be observed with a marked reduction in monoclonal protein levels.

"Importantly, biochemical responses were accompanied by clearance of myeloma cells from the bone marrow," he added.

All three of the patients who received 4 mg/kg of daratumumab experienced reductions in their blood monoclonal protein levels by 49 percent, 64 percent, and 100 percent, respectively. These patients also experienced a significant reduction in the percentage of plasma cells in the bone marrow (80 percent, 89 percent, and 97 percent).

Similarly, all three of the patients who received 8 mg/kg of daratumumab also experienced reductions in their blood monoclonal protein levels by 4 percent, 39 percent, and 100 percent, respectively.

Two out of three patients who received 16 mg/kg of daratumumab experienced reductions in their monoclonal protein levels. One patient had a 50 percent reduction of blood monoclonal proteins, and the other patient had a 33 percent reduction of urine monoclonal proteins.

"The signs of response we see primarily from a dose level of 4 mg/kg and upwards has caused a good deal of optimism among investigators," said Dr. Plesner.

The most common treatment-related side effects included fever (31 percent of patients), cough (21 percent), high blood pressure (14 percent), and nausea (14 percent).

The most common blood-related side effects included low white blood cell counts (21 percent) and low red blood cell counts (17 percent).

Fourteen percent of patients experienced severe side effects, including low red blood cell and platelet counts, abnormal liver function tests, spasms of the airways making breathing difficult, and an inflammatory syndrome.

Two patients experienced a dose-limiting toxicity that required a reduction in daratumumab dosing.

The maximum tolerated dose has not been established yet.

For more information, please see the slide deck for Dr. Plesner's presentation, which he has made available as a courtesy to The Beacon's readers, and abstract 8019 at the ASCO 2012 meeting website



9/6 2012 13:26 Sukkeralf 058098



Link til lidt flrer slides fra præsentationen:

http://static9.light-kr.com/documents/Plesner%20-%20A..



11/6 2012 09:42 gentogen 058130






11/6 2012 10:09 celsius 058131



det er jo en fantastisk udmelding,, jeg vil straks ta´ud og se på den Audi A3 jeg altid har ønsket mig -:)

"Det synes at være den mest lovende monoklonale antistof til behandling af myelomatose til dato og en af ??de mest lovende virkelig nye stoffer til behandling af myelomatose. Det ser ud til at have lav toksicitet og bør kombinere godt med andre regimer," siger Dr. Bergsage"



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57872 Ok, tak ..
5/6 12:56 w 0