AstraZeneca and Daiichi Sankyo drug Enhertu is on a hot streak, winning an FDA approval in lung cancer that marks its second affirmative regulatory decision within the span of a week.
The FDA approval announced Friday covers the treatment of adults whose advanced cases of non-small cell lung cancer (NSCLC) express the cancer protein HER2. Those cancers must have received at least one prior systemic therapy. According to the FDA, Enhertu is now the first drug approved for treating NSCLC characterized by the HER2 mutation. Concurrent with Enhertu’s new approval, the agency also approved a Thermo Fisher Scientific companion diagnostic that detects this mutation.
Enhertu is an antibody drug conjugate, a type of therapy comprised of a targeting antibody linked to a toxic drug payload. The antibody component of Enhertu is designed to target HER2, a protein expressed on the surface of some cancer cells. The drug won its first FDA approval in 2019 for the treatment of HER2-positive breast cancers that have spread. On Aug. 6, the FDA expanded the drug’s approval to include the treatment of breast cancers characterized by levels of HER2 previously thought to be too low for a targeted therapy. That decision defined a new category of breast cancer patients, bringing them their first targeted therapy.
The latest Enhertu approval means the drug may now be used to treat the most common type of lung cancer. NSCLC accounts for about 80% of lung cancer cases, according to the American Lung Association. This approval was based on an interim analysis of data from Phase 2 data that enrolled 152 participants with HER2-positive NSCLC. The main study goal is to measure objective response rate to the drug, defined as the proportion of patients showing either a complete response or a partial response to the infused therapy. The objective response rate was 58% and the median duration of that response was 8.7 months. Response rates were consistent across the two doses that were tested. Higher rates of lung complications were observed at the higher dose; the approval covers the low dose. AstraZeneca said that results from the NSCLC clinical trial will be presented at a future medical meeting.
The most common adverse reactions reported in the clinical trial include nausea, a low white blood cell count, anemia, and low levels of immune cells called neutrophils—all of them consistent with previous tests of the drug. The most serious complication observed in the study was interstitial lung disease, which is characterized by scarring and inflammation. The drug’s label includes a boxed warning flagging this side effect.
“HER2-mutant non-small cell lung cancer is an aggressive form of disease which commonly affects young patients who have faced limited treatment options and a poor prognosis to date,” Dave Fredrickson, executive vice president of AstraZeneca’s oncology business unit, said in a prepared statement. “Today’s news provides these patients with the opportunity to benefit from a targeted therapy and highlights the importance of testing for predictive markers, including HER2 in lung cancer, at the time of diagnosis to ensure patients receive the most appropriate treatment for their specific disease.”
The regulatory decision for Enhertu in NSCLC is an accelerated approval that’s based on less evidence than is required of a standard approval. AstraZeneca and Daiichi Sankyo will need to conduct additional clinical testing to confirm the drug’s benefit to patients. The drug’s first approval in HER2-positive breast cancer was an accelerated one. That status was converted to full approval in May when the drug moved up in the sequence of cancer treatment options with the FDA O.K. of the drug as a second-line therapy. Enhertu is also approved for treating advanced HER2-positive gastric cancers.
Here’s a recap of some additional regulatory news from the past week:
—Tabrecta, a Novartis drug that won accelerated approval in 2020 for the treatment of advanced NSCLC, now has full FDA approval. The targeted therapy is a small molecule designed to target a particular genetic signature known as mesenchymal-epithelial transition (MET) exon 14 skipping. Conversion of the drug’s status to full approval is based on additional clinical testing that showed response rates consistent with earlier data.
—The European Medicines Agency told ProQR Therapeutics that the company needs to run another clinical trial for its RNA therapy for a rare eye disorder. The therapy failed a pivotal study earlier this year but ProQR had hoped that an additional analysis of the clinical data would be enough to support a regulatory submission. Rather than conduct another study, the Netherlands-based biotech said it will look to partner all of its ophthalmology assets and turn its focus to developing liver and central nervous system disorder drugs based on its RNA platform technology.
—The FDA rejected an Acadia Therapeutics application seeking to expand the approval of its anti-psychotic, Nuplazid, to include Alzheimer’s psychosis. According to Acadia, the FDA said that the data submitted were not from an adequate and well-controlled study and the company must run another clinical trial. The drug was first approved in 2016 as a treatment for the hallucinations and delusions experienced by patients who have Parkinson’s disease.
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