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Fra reuters mere af det samme


12341 akademikeren 28/5 2009 16:35
Oversigt


* FDA staff asks if drug benefits enough to back approval

* Glaxo says response rate better than other options

* Genmab shares fall 17.5 pct, Glaxo shares up

(Adds analyst, Glaxo comments; updates shares)

By Lisa Richwine

WASHINGTON, May 27 (Reuters) - U.S. drug reviewers questioned whether a proposed leukemia drug from GlaxoSmithKline PLC (GSK) and Genmab (GEN) provides enough benefit to warrant approval, documents released on Wednesday said.

Shares of Danish biotech company Genmab fell 17.5 percent in Copenhagen, while shares of much larger Glaxo gained 0.9 percent on the New York Stock Exchange.

Food and Drug Administration staff said the magnitude of anti-cancer activity from the drug, Arzerra, was "difficult to quantify" in tests of patients with chronic lymphocytic leukemia, a common type of blood cancer in adults.

"The major issue regarding this application is whether the effect sizes ... are reasonably likely to predict clinical benefit," FDA staff said in a memo prepared for an FDA advisory panel that meets Friday.

The FDA will ask the panel for input on the companies' data. The agency usually follows panel recommendations when deciding whether to approve a drug but does not have to. An FDA ruling is due by Aug. 1.

Analysts believe annual sales of Arzerra could eventually top $2 billion, although the drug is unlikely to reach its full potential until the middle of the next decade. The makers are studying larger populations beyond CLL.

Initially, the companies are seeking approval for CLL patients who have failed two other treatments -- fludarabine and alemtuzumab -- and others who have failed fludarabine and for whom alemtuzumab, sold by Genzyme (GENZ) as Campath, was inappropriate because of their bulky tumors.

FDA staff said Glaxo would need to conduct another study to support approval for the latter group.

Sydbank trader Ole Jensen said the FDA staff comments were "a shock to the market" and were causing uncertainty about the drug among Genmab investors.

"It's very natural that the shares fall this much because this is Genmab's big product," Jensen said.

Nordea analyst Lars Hatholt said the companies may need to do another study but that "does not necessarily mean a delay of the product being launched into the market."

"Uncertainty about the outcome of this has increased, which the share price reflects, but this (FDA) document does not mean the project has been buried," Hatholt said.

Jefferies International analyst Peter Welford said in a research note the share drop was "overdone" and he felt the drug would ultimately be approved for CLL. He reiterated a "buy" recommendation on Genmab.

Glaxo, in a summary prepared for the panel, said Arzerra offered better safety and effectiveness for CLL patients who have failed alternatives and the drug should be approved.

A clinical trial showed a 58 percent response rate to Arzerra in patients who failed the two prior chemotherapy regimens, a higher level than the normal 25 percent level, Glaxo spokeswoman Lisa Behrens said.

But FDA reviewers questioned how the responses were measured. An agency clinical reviewer estimated the response rate to Arzerra at about 41 percent, the staff documents said.

Infections, including fatal ones, were seen frequently in the study but it was not possible to determine how much infection risk was due to the drug, FDA staff said. Heavily treated CLL patients normally have high infection rates.

Genmab spokeswoman Helle Husted said the company had no comment ahead of the meeting.



28/5 2009 16:59 Kenddinvare 012344



Er vi sikre på at der kommer en udtalelse i morgen og kan den tænkes at komme mens OMX er åben?



28/5 2009 17:02 Stinker 012347



Mødet slutter først kl. 12.30 (EST) dvs. kl. 18.30.
http://www.fda.gov/cder/audiences/acspage/meetings/on..



28/5 2009 17:57 tumult 012349



Omkring 100.000 stk handlet i slutauktionen, HURRA for ENS.



28/5 2009 18:00 akademikeren 012350



Ja det var temmeligt godt...



28/5 2009 19:35 Trader17 012351



Undrer mig over hvorfor Solsen ikke har været inde
med nogle indlæg....

MVH Trader 17



28/5 2009 20:07 Solsen 012352



Jeg glæder mig over, at en der har mere faglig indsigt end mig har udtalt sig her på PI (Thro)

FDAs pladder omkring protokollen er vanvittigt, når de selv har godkendt den. CT scanning også pladder, når denne ikke var krævet i protokollen. Etc.

Men de fik da mange Genmab aktier i handelen.

Men man frygter sq ODAC alligevel, når man har set hvad der tidligere er sket.

Men lægerne tror på arzerra.



28/5 2009 20:29 Stinker 012353



Men lægerne har vel ikke mere at bygge deres tro på end IRC havde?

Jeg tænker som dig, at FDA måtte have grebet ind tidligere, hvis der var noget fundamentalt galt med protokollen. På den baggrund er det dog alligevel rystende, hvis det også for Genmab og GSK var en overraskelse, at der ikke kan meddeles en godkendelse for så vidt angår BFR-gruppen.
Under alle omstændigheder skal der udføres nogle fase 4 forsøg til erstatning for de surrogatmål man nu læner sig op ad. ODAC's eventuelle bemærkninger desangående får markedet nok nemt galt i halsen.



28/5 2009 20:38 Solsen 012354



Sikkert

Argumenterne der fremføres er tynde. Men udfaldet af ODAC mødet kan meget vel blive fase 4 og det gør såmænd heller ikke noget.

Det bliver interessant om markedet evt. kan finde ud af det !

FDA har løbende fået oplysninger fra Genmab/GSK og de har under forsøget godkendt en protokolændring !!!



28/5 2009 20:52 akademikeren 012355



Jeg vil prøve at finde hoved og hale i det her. I November 2005 Pre-phase 2 meeting godkender FDA protokollen.
• FDA identified durable objective response rate as an acceptable surrogate endpoint reasonable likely to predict clinical benefit in a patient population with an unmet medical need, i.e., no alternative therapy.

Genmab har siden September 2008 vidst at “ The patient population studied in the BFR subgroup did not meet the regulatory standard for having an unmet medical need; the protocol only required prior therapy with one drug (fludarabine).”

FDA will rely on the investigator-reported ORR and response duration as the basis for approval and for labeling claims.

Dvs. 42%....højt højt over det krævede.

However, as will be described subsequently in this document (in the FDA Special Considerations Section),five responding patients may have been re-classified as non-responders if follow-up CT
scan results were included in the FDA clinical reviewer’s response determinations. Removing these five patients from the FDA clinical reviewer’s responder group would
yield a 32% ORR

stadig højt over det krævede...som følger nedenfor:

Overall response rates of 10-20% were unlikely to predict clinical
benefit. In a population with unmet need, an observed response rate where the lower bound of the 95% CI for the ORR was at least 25% would be of interest.

The FDA efficacy results will focus on the DR subgroup patient population.

It must be emphasized that these documents do not represent FDA’s final analyses, final decisions, or Office conclusions, and that no regulatory decision on the status of this application has been made. Indeed, an important piece of our thinking on these applications will be a full consideration of whatever advice the ODAC provides on these important issues.





28/5 2009 20:56 Stinker 012356



Kan du gennemskue 1) med hvilket formål man tilføjede BFR-gruppen til studiet, samt 2) hvorfor man valgte at forfølge muligheden for accelerated approval og dermed basere godkendelsen på surrogatmål (orr) i stedet for Overall Survival (OS) eller Progression Free Survival (PFS) ?
Jeg går ud fra at man i de to sidstnævnte tilfæde ville være nød til at tilføje en ekstra (placebo) arm til studiet, men nogen forlængelse af proceduren ville der vel ikke være blevet tale om, givet at patienterne jo allerede er døde. Som jeg forstår systemet vil en godkendelse på grundlag af surrogatmål alligevel blive gjort betinget af, at man efterfølgende gennemfører sådanne studier, som kan vise "direct evidence of clinical benefit".



28/5 2009 21:00 akademikeren 012357



man tilføjer BFR for at opnå dette, som også står i rapporten...side 33+34

"Data from the BFR patient population and from “other” CLL
patients enrolled in study Hx-CD20-406 and data from patients enrolled in study Hx34
CD20-402 will be considered supportive in the decision making regarding approval of
ofatumumab in the DR patient population."



28/5 2009 21:05 akademikeren 012358



2) man bruger vel orr, fordi det speeder processen op og man skal ikke vente på endpoints i OS m.v.



28/5 2009 21:19 Stinker 012360



Processen speedes vel ikke op ved brugen af orr, når folk alligevel dør få måneder efter at man kan konstatere et tilfælde af partial response, hvorved også OS/PFS skulle tilgængelig kort tid efter.

Mht. BFR-gruppen har jeg også hæftet mig ved, at man vil inddrage resultaterne herfra. Det fremgår dog ikke klart, hvad man vil bruge dem til. Kunne DR-gruppen ikke blot i stedet være gjort større, dersom man ville have flere data, eller skyldes indlemmelsen af BFR-gruppen slet og ret mangel på DR-patienter?



28/5 2009 21:31 akademikeren 012361



Jeg tror bare ikke det er et issue..da FDA jo selv har godkendt protokollen i 2005. Det er måske fordi man vil have sammenligningsgrundlaget på plads for de andre stoffer der er godkendt i CLL



28/5 2009 22:19 Solsen 012368



"Kunne DR-gruppen ikke blot i stedet være gjort større, dersom man ville have flere data, eller skyldes indlemmelsen af BFR-gruppen slet og ret mangel på DR-patienter? "

Tror du har ret her stinker !



29/5 2009 15:27 grammie 012408



- Godt spørgsmål hvorfor man valgte at bruge ORR - og at FDA sagde god for det. Man har vel data på overlevelse fra patienterne, så at lave statistik på dem skulle være lige til...?
- Hvis man kan analysere ORR uden kontrolgruppe, så kan man vel også analysere survival uden kontrolgruppe...?
- Havde de kigget på survival så undgik man også hele baladen om scanning vs. klinisk kontrol af ORR - overlevelse er ikke sådan at diskutere.
- Aka skriver at 32% er langt over de krævede 25% - men de 25% er lower band CI. De 32% (justeret fra 42%) er vel fundet empirisk, men hvad er CI?



29/5 2009 16:40 tumult 012410



Dk flash skriver kl 15:30 at mødet begynder om 1 ½ time, det må være kl 17 dansk tid, er det rigtigt.?



29/5 2009 16:44 Stinker 012411



Nej, mødet begyndte kl 8 (Orlando, Florida dvs GMT +5t dvs kl 14)
http://www.fda.gov/cder/audiences/acspage/meetings/on..



29/5 2009 16:47 Stinker 012412



Det var vist noget vrøvl jeg fik skrevet med GMT, men resultatet må rigtigt: Mådestart kl 14 dansk tid.



28/5 2009 17:00 tumult 012345



Den er fra i går aftes, hvor jeg smed et link til den i en tidligere tråd.
Der står at GSK steg 0,9% i går, men den sluttede nu i 0.
Idag er den også helt upåvirket af gårsdagens begivenhed.

http://www.nyse.com/about/listed/lcddata.html?ticker=..



28/5 2009 17:09 Sukkeralf 012348



Nu er markedsværdien jo meget meget større for GSK end den er for Genmab - og vigtigheden af Arzerra er i princippet langt mere vigtig for Genmab end for GSK.

Så en sådan begivenhed vil ikke tynge GSK på nuværende tidspunkt - hvis fredagens udtalelse fra komitéen er negativ, så måske et lille fald hos GSK. Omvendt vil du sikkert heller ikke se den store stigning hos GSK, hvis udtalelserne bliver opmundrerne.

Mvh
Sukkeralf



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