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Posts Tagged ‘FDA approval Denied’


Good and Bad News Reported for Ovarian Cancer Therapy

Reporter, Curator: Stephen J. Williams, Ph.D.

 

In a recent Fierce Biotech report

FDA review red-flags AstraZeneca’s case for ovarian cancer drug olaparib”,

John Carroll reports on a disappointing ruling by the FDA on AstraZeneca’s PARP inhibitor olaparib for maintenance therapy in women with cisplatin refractory ovarian cancer with BRCA mutation.   Early clinical investigations had pointed to efficacy of PARP inhibitors in ovarian tumors carrying the BRCA mutation. The scientific rationale was quite clear:

A good review explaining the pharmacology behind the rationale of PARP inhibitors in BRCA deficient breast and ovarian cancer is given by Drs. Christina Annunziata and Susan E, Bates in PARP inhibitors in BRCA1/BRCA2 germline mutation carriers with ovarian and breast cancer

(http://f1000.com/prime/reports/b/2/10/)

 

Dr. Sudipta Saha’s postBRCA1 a tumour suppressor in breast and ovarian cancer – functions in transcription, ubiquitination and DNA repair discusses how BRCA1 affects the double strand DNA repair process, augments histone modification, as well as affecting expression of DNA repair genes.

Dana Farber’s Dr. Ralph Scully, Ph.D., in Exploiting DNA Repair Targets in Breast Cancer (http://www.dfhcc.harvard.edu/news/news/article/5402/), explains his research investigating why multiple DNA repair pathways may have to be targeted with PARP therapy concurrent with BRCA1 deficiency.

 

 

However FDA investigators voiced their skepticism of AstraZeneca’s clinical results, namely

  • Small number of patients enrolled
  • BRCA1/2 cohort were identified retrospectively
  • results skewed by false benefit from “underperforming” control arm
  • possible inadvertent selection bias
  • hazard ratio suggesting improvement in progression free survival but higher risk/benefit

The FDA investigators released their report two days before an expert panel would be releasing their own report (reported in the link below from FierceBiotech)

UPDATED: FDA experts spurn AstraZeneca’s pitch for ovarian cancer drug olaparib

in which the expert panel reiterated the findings of the FDA investigators.   The expert panel’s job was to find if there was any clinical benefit for continuing consideration of olaparib, basically stating

“This trial has problems,” noted FDA cancer chief Richard Pazdur during the panel discussion. If investigators had “pristine evidence of a 7-month advantage in PFS, we wouldn’t be here.”

The expert panel was concerned for the above reasons as well as the reported handful of lethal cases of myelodysplastic syndrome and acute myeloid leukemia in the study, although the panel noted these patients had advanced disease before entering the trial, raising the possibility that prior drugs may have triggered their deaths.

 

As John Carrol from FierceBiotech notes, the decision may spark renewed interest by Pfizer of a bid for AstraZeneca as the potential FDA rejection would certainly dampen AstraZeneca’s future growth and profit plans. Last month AstraZeneca’s CEO made the case to shareholders to reject the Pfizer offer by pointing to AstraZeneca’s potential beefed-up pipeline.

 

However, on the same day, FierceBiotechreports some great news (at least in Europe) on the ovarian cancer front:

 

EU backs Roche’s Avastin for hard-to-treat ovarian cancer

As Arlene Weintraub   of FierceBiotechreports:

EU Committee for Medicinal Products for Human Use (CHMP) handed down a positive ruling on Avastin, recommending that the European Commission approve the drug for use in women with ovarian cancer that’s resistant to platinum-based chemotherapy. It’s the first biologic to receive a positive opinion from the CHMP for this hard-to-treat form of the disease.

Please see here for official press release: CHMP recommends EU approval of Roche’s Avastin for platinum-resistant recurrent ovarian cancer

 

EU had been getting pressure from British doctors to approve Avastin based on clinical trial results although it may be important to note that the EU zone seems to have an ability to recruit more numbers for clinical trials than in US. For instance a wonen’s breast cancer prevention trial had heavy recruitment in what would be considered a short time frame compared to the US.

 

 

 

Sources

http://www.fiercebiotech.com/story/fda-review-red-flags-astrazenecas-case-ovarian-cancer-drug-olaparib/2014-06-23

 

http://www.fiercebiotech.com/story/fda-experts-spurn-astrazenecas-pitch-ovarian-cancer-drug-olaparib/2014-06-25

 

http://www.fiercepharma.com/story/eu-backs-roches-avastin-hard-treat-ovarian-cancer/2014-06-27

 

 

Some other posts relating to OVARIAN CANCER on this site include

Efficacy of Ovariectomy in Presence of BRCA1 vs BRCA2 and the Risk for Ovarian Cancer

Testing for Multiple Genetic Mutations via NGS for Patients: Very Strong Family History of Breast & Ovarian Cancer, Diagnosed at Young Ages, & Negative on BRCA Test

Ultrasound-based Screening for Ovarian Cancer

Dasatinib in Combination With Other Drugs for Advanced, Recurrent Ovarian Cancer

BRCA1 a tumour suppressor in breast and ovarian cancer – functions in transcription, ubiquitination and DNA repair

 

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Breaching Drug Disclosure on Tresiba been refused U.S. approval – Novo Nordisk A/S (NVO) Reported To Police

Reporter: Aviva Lev-Ari, PhD, RN

SOURCE

http://www.biospace.com/news_story.aspx?NewsEntityId=318189&type=email&source=GP_121013

Novo Nordisk A/S (NVO) Reported To Police For Breaching Drug Disclosure Rules

12/10/2013 7:32:19 AM

Novo Nordisk, the world’s largest insulin maker, is facing a Danish police probe after it was reported by the financial watchdog for not disclosing at once that its big new product hope Tresiba had been refused U.S. approval.

Although the probe is unlikely to have a serious financial impact on the company, the largest by market value in the Nordic region, it may tarnish its reputation and could leave it open to lawsuits from investors in the United States, where its shares also trade.

The Danish Financial Supervisory Authority (FSA) said on Tuesday Novo should have issued a statement about the U.S. decision not to approve Tresiba, its new long-acting insulin, on the evening of Friday, February 8 instead of waiting until Sunday, February 10.

 

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