FDA watch: New medication approvals

It’s tempting to think that the FDA is home to staid and urbane discussion. But this is not always the case, as showcased with the FDA’s June 2021 approval of Biogen’s controversial Alzheimer drug, aducanumab—an infusion that breaks the bank at $56,000 per year. Various experts claim that there is weak evidence supporting its approval, with three FDA advisors calling it quits in outrage following the drug’s recent approval.

On November 20, 2020, the FDA’s own advisory committee came down harshly against the drug. According to their minutes:

“Almost all of the committee members voted ‘No’, agreeing that it is not reasonable to consider Study 302 as primary evidence of effectiveness of aducanumab for the treatment of Alzheimer’s disease. These members were not persuaded by the analyses provided and expressed their reluctancy to suggest approval of aducanumab for the treatment of Alzheimer’s disease due to the insubstantial evidence shown.” Further, these members expressed difficulty drawing a conclusion on the information provided due to “un-addressed criticisms provided by the statistical analysis of the studies.”

Ouch! Fortunately, not all FDA approvals are so contentious. Let’s look at some recent approvals starting with the one that caused an uproar—aducanumab.

Aducanumab (Aduhelm)

The FDA granted accelerated approval to this Alzheimer drug on the basis of three separate double-blind, randomized, placebo-controlled dose-ranging studies trials involving 3,482 patients. Those participants who were administered the treatment experienced dose- and time-dependent decreases of amyloid beta plaques compared with the control group, per the FDA’s press release. 

These plaque reductions were demonstrated via positron emission tomography (PET) imaging. PET imaging estimated the brain levels of amyloid beta plaque in a composite of brain regions suggested to be affected by Alzheimer pathology vs those regions expected to be spared. 

Sotorasib (Lumakras)

For a long time, there was little hope for the treatment of non-small cell lung cancer (NSCLC) harboring a genetic mutation called KRAS G12C. 

As recently as 2019, here’s what researchers had to say about targeting KRAS: “Despite decades of research, no approved drugs have been discovered for KRAS. Recently, a pocket occurring on the surface of the active and inactive form of KRAS was found, but, due to its comparatively shallow, polar nature, this pocket has been assumed to be ‘undruggable.’”

Then came sotorasib. This drug blocks KRAS G12C in an inactive GDP-bound state, consequently permanently inhibiting it. The FDA approval was based on a study involving 124 patients with locally advanced or metastatic KRAS G12C-mutated NSCLC that progressed, despite receiving a previous immune checkpoint inhibitor, platinum-based chemotherapy, or both. The objective response rate was 36%. Furthermore, 58% of patients had a duration of response of 6 or more months.

Amivantamab-vmjw (Rybrevant)

Biologics have transmogrified cancer care. The approval of amivantamab-vmjw as the first treatment for adult patients with NSCLC with “epidermal growth factor receptor (EGFR) exon 20 insertion mutations” exemplifies this change.

“Advances in precision oncology continue to facilitate drug development, allowing diseases like lung cancer to be subset into biomarker-defined populations appropriate for targeted therapies,” said Julia Beaver, MD, of the FDA in a press release. “With today’s approval, for the first time, patients with non-small cell lung cancer with EGFR exon 20 insertion mutations will have a targeted treatment option.”

The FDA approved this agent based on a study of 81 patients with NSCLC harboring EGFR exon 20 insertion mutations, whose disease had progressed during or after platinum-based chemotherapy. The overall response rate was 40%, and the median duration of response was 11.1 months. Of note, 63% of patients exhibited a duration of response lasting 6 or more months.

Dostarlimab (Jemperli)

Another biologic making waves is dostarlimab. It was recently approved for patients with recurrent or advanced endometrial cancer that has progressed on or after previous treatment with a platinum-containing chemotherapy. It hones in on cancers that harbor a feature known as dMMR, which renders abnormalities that impair the proper repair of DNA in cells. 

This agent works by blocking PD-1/PD-L1 pathways, which are proteins located on immune and some cancer cells. Its approval was based on its safety and efficacy in a single-arm, multi-cohort clinical trial, in which 71 patients with dMMR recurrent or advanced endometrial cancer took the drug. Overall, 42.3% experienced complete response (ie, tumor disappearance) or a partial response (ie, tumor shrinkage) following treatment with dostarlimab. Response to the agent lasted 6 or more months in 93% of those responsive.

Read more about drugs that were approved by the FDA in 2020, at MDLinx.