March 9, 2017
By Mark Terry, BioSpace.com Breaking News Staff
President Trump recently called the U.S. Food and Drug Administration (FDA) drug approval process “slow and burdensome.” Although he has yet to choose an FDA commissioner, two names bandied about, Jim O’Neil and Scott Gottlieb, are viewed as “disruptors” who have called for a number of questionable changes, including approving drugs based on safety, not on whether they are effective.
Adam Feuerstein, writing for TheStreet, examines nine companies that might wish that were the case. He writes, they “have a common mission: to convince the U.S. Food and Drug Administration to grant approval of their respective drugs based on clinical data requiring the agency to bend, tweak or even maybe lower current standards.”
Alkermes ’ (ALKS) drug is ALKS-5461 for treatment-resistant depression. Two of three clinical trials failed to meet their primary endpoints. The company argues that the “totality” of the data shows the drug is effective, and plans to share the pooled data with the FDA in the second quarter.
In January, CytRx announced the FDA had agreed to a Type B pre-NDA meeting where it will try to convince the administration that it should go along with a New Drug Application (NDA) for aldoxorubicin as a new second-line treatment for patients with soft tissue sarcomas (STS). The drug failed a Phase III study. Feuerstein writes, “Instead of accepting defeat gracefully, CytRx deleted half the patients enrolled in the study and re-analyzed the data to produce an outcome showing aldoxorubicin worked.”
The FDA has already twice rejected the company’s filing for HEPSLISAV-B for Hepatitis B. On February 28, Dynavax Technologies announced the FDA had agreed to review its responses to the Complete Response Letter (CRL) the FDA put out in November 2016. The PDUFA data is August 10, 2017.
Although in September 2015, 4. Intra-Cellular Therapies’ ITI-007 for schizophrenia made it through a Phase III study, in September 2016, it failed. Feuerstein writes, “Later this month, Intra-Cellular is meeting with the FDA to discuss the mixed bag of ITI-007 clinical trial results and get agency feedback on filing a new drug application.”
In its report, Intra-Cellular argued that, “We believe ITI-007 did not separate from placebo on the pre-specified primary endpoint in Study ‘302 in part due to an unusually high placebo response at certain sites which disproportionately affected the trial results and contributed to the efficacy outcome of this study compared to our two previous positive efficacy studies.”
On January 27, Novan Therapeutics announced top-line results from two of its Phase III trials for SB204 to treat acne vulgaris. The nitric oxide-releasing product showed statistical significant improvement on all three co-primary endpoints in NI-AC302, but only showed statistical significance on one of three co-primary endpoints in NI-AC301.
Now the company is going back to the FDA to try and explain the inconsistent results, and hopes to get approval for the drug in the first quarter of next year without conducting another trial.
Portola Pharmaceuticals ' betrixaban, an anticoagulant, just scraped by a Phase III study last year, “although,” Feuerstein writes, “an ‘exploratory’ analysis of the same data showed a positive reduced risk for blood clots.”
In this case, there seems to be somewhat mixed signals from the FDA. The company submitted an NDA and the FDA accepted it. Then the FDA announced it would not hold an advisory committee meeting. Does that mean the results are so great it won’t be necessary, or the results are so bad they won’t bother? Everyone will find out on June 24.
On March 6, PTC Therapeutics announced that the FDA “has acknowledge the filing over protest of PTC’s New Drug Application (NDA) for Translarna (ataluren)” for Duchenne muscular dystrophy. Probably emboldened by the FDA’s approval of Sarepta Therapeutics’ (SRPT) Exondys 51 on limited and questionable data, PTC has twisted the agency’s arm into considering the drug, although as Feuerstein writes, “PTC’s drug has never demonstrated a statistically significant benefit for patients.” The decision is expected on October 24.
The drug in question is fostamatinib for immune thrombocytopenia. On January 30, Rigel Pharmaceuticals indicated that it was updating data from its clinical program, and that “study results continue to trend positive.”
The company has indicated it plans to submit an NDA by the end of the month. Feuerstein writes, “Like others in the Gnarly Nine, that application will consist of mixed data from Phase III studies that achieved and missed primary endpoints.”
On March 6, TG Therapeutics announced top-line data from its Phase III GENUINE trial of TG-1101 in combination with Ibrutinib in high risk chronic lymphocytic leukemia (CLL). The trial met its primary endpoint, showing a statistically significant improvement in Overall Response Rate (ORR) compared to Ibrutinib alone in two different populations, Intent to Treat (ITT) and Treated population.
Feuerstein writes, “What happens when a company seeks accelerated approval for a cancer drug in a patient population where there is no unmet medical need, and where older drugs might actually benefit patients more?”
TG plans to submit its plans for TG-1101 to the FDA soon, and then we’ll all know.
