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Q&A med Genmab A/S, 26 Februar Kl. 14:30 Læs mere her

Daratumumab mv

69012 Solsen 29/5 2014 08:01

Principal Investigator på monotrial i dara Paul Richardson,Dana-Farber har gjort følgende video på dette link:

Han udtaler bl.a:

So it's important to think of daratumumab as a separate antibody targeting a very distinct target and the same for the SAR compound which is also targeting CD38. And interestingly, dara and SAR do have quality differences between them at least preclinically. We fairly don't know what to expect quite yet clinically. But the good news is that both antibodies are showing that the target would this particular technology or this particular monoclonal platform because CD38 has been targeted years ago by different antibodies and they didn't work.

This current group of new antibodies targeting CD38 are phenomenally active and what we're seeing is that both with SAR and with daratumumab there is single agent activity which is a step up from what we saw with elotuzumab, and there's a lot of reasons for this we think. Number one, CD38 is such an important target in myeloma. The other thing is that CD38 is a very important receptor in growth of tissues generally speaking. It's a very interesting concept but when you're an infant or young, there's a lot of CD38 expression on a lot of different tissues. As you get older, CD38 expression goes broadly down, so hopefully at our age Jenny, there is very little CD38 going on.

Unfortunately, when you get myeloma that changes and CD38 is expressed by the myeloma, and then the hypothesis is there's a lot of CD38 expression in the neighborhood as well that may be part of the reason why this is such an attractive target. Because as you may have noticed drugs that really work well in myeloma are those that hit both the neighborhood and the tumor. So for example, proteasomes do that, IMiDs do that, and dara and SAR hit both. And that I think is a real - or perhaps hit both. We don't really completely know that but that's a good working hypothesis. So when you've got antibodies that do this and really shoot both sides of the coin, if you will, then I think there's a real promise to these especially if you can then combine them.

So just focusing on daratumumab first, that antibody is now really moving forward in Phase III studies now actually as I speak, having completed very quick Phase I and II development, recognizing that the early Phase I of development to the antibody was necessarily very slow because this is a first-in-man experience. So based upon that, we are now accelerating very quickly and we have combinations of dara with lenalidomide, combinations of dara coming forward now with bortezomib, and basically there will be combinations of dara with lenalidomide and bortezomib, the so-called RVD plus dara, and these will be very powerful platforms for future treatment.

The initial results from lenalidomide plus dara in our own center, these studies are being led by my colleague, Jacob Laubach and Jacob is phenomenal in doing a wonderful job with all of these. Basically what he's showing is that when you put daratumumab with lenalidomide, there's tremendous activity being seen. Hence, similarly daratumumab even as a single-agent, just like our partners in the same trial who are actually from Denmark and Holland are showing exactly the same thing, as part of the same study, we're all working as one team. But what we're showing is that dara really works on its own, and dara combined with lenalidomide is very powerful as well. And then larger trials are currently ongoing led by our partners here in the US, Janssen who are leading these and moving these across the country so that this drug can get as quickly as possible to approval.

One very exciting thing about dara is that the FDA drawn to the breakthrough status because it's uniquely targeting a mechanism in myeloma that no other drug until dara came was. So it was given what's called breakthrough status. SAR, the Sanofi compound is hot on its heels and it too is showing really encouraging activity and this is being led by our colleagues at USCF and at Mayo; Dr. Tom Martin at UCSF and Dr. Joe Mikhael at Mayo have led trials with SAR alone and shown what we saw with dara, single-agent activity about half the patients responding. Then when you combine it with these other drugs you're seeing real synergy...........Citat slut

Interessant at ph1/2 er slut jf ovenfor så mangler vi blot ph2 16 mg for at kunne tælle ned til readout og approvalproces.

Nordea har sandsynlighed på 60% på dara i MM og hvis der opnås succes - altså 100% i DCF modellen - ændres target til +400 DKK.

Så mangler der blot øvrige sygdomstargets, som vi sandsynligvis også vil se Janssen gå efter, bl.a. NHL.

Arzerra er blevet "show me the money" så selv beståede fase 3 vil næppe rykke kursen voldsomt. En GSK melding på RRMS kan måske rykke lidt. Men ellers skal vi se stigende salg før kursstigninger kommer herfra - jeg tror markedet undervurderer Arzerra og ser ikke stoffets potentiale i kombi med Ibrutinib/Idelalisib. First line Bendamustine+Arzerra er billig og super effektiv med stort potentiale.


29/5 2014 14:07 Sukkeralf 369015

Tak Solsen

Her er hvad Ohad Hammer skriver i sin blog:

CD38 antibodies - Sanofi emerges as a worthy opponent

This year's meeting will hae updated results for the 2 leading CD38 antibodies for multiple myeloma.

Genamb's (GEN)/J&J's daratumumab will have 2 oral presentations as monotherapy and in combination with Revlimid. The abstract for the monotherapy study reports mixed efficacy data for 2 expansion cohorts (8 and 16 mg/kg). The combined response rate for the two cohorts was only 19% (compared to 33% for ≥4 mg/kg at ASH 2012). Nevertheless, the 16 mg/kg arm had a response rate of 46%, which suggests a dose dependent response but sample size is small (13 patients). The daratumumab+Revlimid combination continues to look active with responses in 8 (72%) of 11 patients.

Sanofi's (SNY) /Immunogen (IMGN) SAR650984 will also have data as monotherapy or in combination with Revlimid. The abstract for the monotherapy study reports a 24% response rate including a 33% response rate for doses ≥ 10mg/kg. Of note, 2 patients achieved a complete response whereas in daratumumab's data set there were none. Efficacy in combination with Revlimid was 58% (7/12 patients). This is numerically lower than daratumumab+Revlimid but the small sample size makes it hard to compare the 2 drugs. In addition, patients in the SAR650984 trials appear more heavily pre-treated.

Although both agents are active in multiple myeloma, daratumumab has a clear development lead with 2 phase III trials (still not active) and a pivotal phase II trial in relapsed/refractory patients.

Of note, there are still no published data for Celgene/Morphosys' (MOR.DE) anti-CD38 antibody. The antibody was licensed by Celgene in a huge licensing deal last year.

Det bliver spændende at følge fredag og mandag :-)