After approving a record number of new agents in 2015, FDA's first decision on a new molecular entity in 2016 is a non-approval action: a complete response letter for BioMarin Pharmaceutical Inc.'s Kyndrisa.

Kyndrisa (drisapersen) is only the second product with a breakthrough therapy designation known to have received a complete response letter.

BioMarin Kyndrisa Did Not Show Substantial Evidence Of Efficacy, FDA Finds

The complete response letter for Kyndrisa, announced Jan. 14, concludes that "the standard of substantial evidence of effectiveness has not been met," BioMarin said. The company indicated that another trial will be necessary for the exon-skipping therapy for Duchenne muscular dystrophy patients with mutations in the dystrophin gene that are amenable to exon 51 skipping Also see "BioMarin's Drisapersen 'Compete Response' Shows FDA Flexibility Still Limited" - Pink Sheet, 14 January, 2016..

The complete response letter is not unexpected after FDA's advisory committee questioned the strength of the clinical data and suggested that more work was needed to determine subgroups that respond to therapy ([A#14151124005]).

Nonetheless, when BioMarin said that FDA would miss the Dec. 27 user fee goal, Kyndrisa's prospects briefly looked up – FDA has shown willingness to miss user fee goals if negotiations or analysis is ongoing that could lead to approval. Instead, BioMarin and will meet with FDA to discuss the CRL and to understand what a new trial should include.

The Kyndrisa decision casts a pall over the upcoming Jan. 22 advisory committee review of another exon-skipping DMD therapy, Sarepta Therapeutics Inc.'s eteplirsen – and the briefing documents, which FDA posted unusually early, made things look even worse ([A#14160115002]).

(See the User Fee Goals chart on the FDA Performance Tracker for information on pending applications. The 'Breakthrough Therapy' chart provides detailed information on products receiving the designation.)

Genentech Earns Priority Reviews For Venetoclax, New Gazyva Use

Genentech Inc. and AbbVie Inc.'s new drug application (NDA) for the Bcl-2 inhibitor venetoclax has officially earned priority review status from FDA, Genentech announced Jan. 12. The rolling NDA was completed at the end of October, which would put the user fee goal at the end of June 2016.

Venetoclax made a splash at the American Society of Hematology annual meeting in December with results of the pivotal Phase II study that forms the basis of the NDA for treatment of patients with chronic lymphocytic leukemia (CLL) who have received at least one prior therapy, including hard-to-treat patients with 17p deletions ([A#00151214011]).

FDA designated venetoclax a breakthrough therapy for previously treated 17p deletion CLL patients.

Genentech also reported that its supplemental biologics license application (sBLA) for the anti-CD20 monoclonal antibody Gazyva (obinutuzumab) received priority review for treatment of follicular lymphoma patients who relapsed after or are refractory to a regimen containing Rituxan (rituximab).

Gilead Looks To Expand TAF To Hepatitis B Treatment

Gilead's tenofovir alefenamide (TAF) is on its way to replacing the company's venerable reverse transcriptase inhibitor Viread (tenofovir disoproxil fumarate) in HIV treatment. TAF was approved as part of the Genvoya four-drug combo in November 2015, and two- and three-drug combos with TAF are pending with user fee goals this coming spring. Now the company is looking to expand TAF into hepatitis B virus (HBV) treatment.

TAF, a targeted prodrug of tenofovir, can be used at a lower dose than Viread and has shown improvement in surrogate laboratory markers of renal and bone safety, according to Gilead.

The NDA for TAF in HBV seeks use as a once-daily treatment for adults with chronic HBV, Gilead announced Jan. 12. Viread is approved for chronic HBV treatment in adults and pediatric patients aged 12 years and older.

Gilead conducted two Phase III studies of TAF in HBV, both showing non-inferiority to Viread in treatment-experienced and treatment-naïve adults with HBeAg-negative and HBeAg-positive chronic HBV.

Adamis' Re-Engineered Emergency Epinephrine Goes Back To FDA

Adamis Pharmaceuticals Corp.'s pre-filled epinephrine single-dose syringe product for emergency treatment of anaphylaxis has a June 4, 2016 user fee goal following the company's Class 2 resubmission to FDA's March 2015 complete response letter.

Adamis "took approximately five months to re-engineer the design of the product, manufacture prototypes, and test the new design," the company noted Jan. 14. The re-engineering of the product responded to FDA's concerns about "the volume of dose delivered by the syringe, including the ability to deliver volume within the levels contained in the labeling claim and as required by FDA."

(See the Complete Response Letters chart on the FDA Performance Tracker for more information on applications that have received action letters from FDA.)

Keeping Track: Gilead Aims To Expand TAF To HBV; BioMarin's Kyndrisa Get Complete Reponse

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