May Approvals, Rejections and Delays

The FDA approved Sanofi’s dengue vaccine on 5/1/2019 for patients 9 through 16 years who have previously had laboratory-confirmed dengue infection and who live in endemic areas such as the US territories of American Samoa, Guam, Puerto Rico, and the US Virgin Islands.

The FDA approved tafamidis meglumine (Vynaqel, Pfizer) and tafamidis (Vyndamax, Pfizer) early on 5/6/2019 for the treatment of the cardiomyopathy of wild-type or hereditary transthyretin-mediated amyloidosis (ATTR-CM) in adults to reduce cardiovascular mortality and cardiovascular-related hospitalization. In the 30-month, 441 patient, Phase III, ATTR-ACT trial, tafamidis reduced all-cause mortality (30% vs 43%) compared to placebo. Tadamidis also reduced cardiovascular-related hospitalizations, decline in 6-minute walk test and decline in the Kansas City Cardiomyopathy Questionnaire–Overall Summary that measures health status.

the FDA approved onasemnogene abeparvovec (Zolgensma, Novartis) on 5/24/2019 for the treatment of patients under the age of two with bi-allelic mutations in the SMN1 gene. This would include babies with Type 1, 2 or 3 spinal muscular atrophy (SMA). Onasemnogene abeparvovec is administered as a single intravenous infusion. The drug was approved with a black box warning regarding acute serious liver injury. ICER released an addendum to the SMA review after the approval of onasemnogene abeparvovec based on additional clinical data. ICER estimated the drug cost at $1.1 to $1.9 million compared to best supportive care to reach the $100,000 to $150,000 cost effective quality-adjusted life year thresholds and $1.2 million to $2.1 million to be cost effective as the life-year gained threshold. Novartis priced onasemnogene abeparvovec at $2.125 million per dose with the total price paid over five annual installments of $425,000 The price is lower than the $4-5 million cost to treat an SMA patient for 10 years and similar to the higher ICER estimates. Onasemnogene abeparvovec will initially be available at 60 medical centers. The sites will send blood for genetic manipulation to Novartis, who will then deliver the re-engineered treatment to the center. 

The FDA approved alpelisib (Piqray, Novartis) on 5/24/2019 to be used in combination with fulvestrant for the treatment of postmenopausal women, and men, with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative, PIK3CA-mutated, advanced or metastatic breast cancer following tumor advancement after endocrine-based regimens. The companion diagnostic test, therascreen PIK3CA RGQ PCR Kit, was also approved to detect the PIK3CA mutation in a tissue and/or a liquid biopsy.

Rejections & Delays

The FDA rejected the NDA for injectable fosfomycin due to facility inspections and manufacturing deficiencies with its contracted manufacturer for the drug.

Acacia filed an NDA for amisulpride in January 2018. The FDA rejected amisulpride's NDA in October 2018 due to manufacturing issues by it contract manufacturer. Acacia refiled an NDA in November 2018, but in May 2019, the FDA again rejected the drug due to continuing deficiencies at the contract manufacturer. Acacia is now working to get another manufacturer approved by the FDA.

The FDA informed ImmunoGen that it would not accept sub-group data from patients with high levels of folate receptor alpha enrolled in the failed FORWARD I trial evaluating mirvetuximab soravtansine for NDA approval. ImmunoGen will need to run a new Phase III trial in patients with high folate receptor alpha expression, platinum-resistant ovarian cancer before seeking approval.

An FDA review of quizartinib questioned the credibility of some clinical trial data due to inconsistencies, lack of efficacy for secondary endpoints and imbalances between the study arms. The FDA’s Oncology Drug Advisory Committee voted 3 to 8 against recommending approval of quizartinib for the treatment of relapsed or refractory acute myeloid leukemia in May 2019.

Another FDA review of pexidartinib expressed concern about data lacking for physical function, stiffness and range of motion and changes in the statistical analysis plan. The FDA’s Oncology Drug Advisory Committee voted 12 to 3 to recommending approval of pexidartinib for the treatment of giant cell tumor of the tendon sheath May 2019
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The FDA has put a partial hold on an axalimogene filolisbac Phase III cervical cancer trial in January 2019, until Advaxis provided additional chemistry, manufacturing and controls information. Under the hold, no new patients could be enrolled in the trial, but current patients can continue to be treated. The FDA lifted the partial band on the cervical cancer trial on 5/15/2019.