Indications and contraindications of latest FDA-approved drugs

The COVID-19 pandemic has put a crimp in many industries, but not drug development. The FDA continues to work diligently to help bring new drugs to the table.

“Innovation drives progress,” the agency wrote in a roundup of new drugs approved in 2020. “When it comes to innovation in the development of new drugs and therapeutic biological products, FDA’s Center for Drug Evaluation and Research (CDER) supports the pharmaceutical industry at every step of the process. With its understanding of the science used to create new products, testing and manufacturing procedures, and the diseases and conditions that new products are designed to treat, CDER provides scientific and regulatory advice needed to bring new therapies to market.”

Here’s a list of five innovative drugs the FDA has approved in 2020, along with indications, adverse effects, and contraindications. All of these drugs were met with much fanfare—in FDA terms, at least—and received official press releases from the agency.

Rukobia (fostemsavir) for HIV

This novel antiretroviral is for adults with long-standing HIV who have tried multiple previous HIV drugs yet are resistant, intolerant, or at risk with such regimens.

Approval was based on a clinical trial involving 371 patients, of which 71% had HIV for more than 15 years, 85% had previously tried five or more different HIV treatment regimens, and 86% had a history of AIDS. After 24 weeks of treatment with fostemsavir in addition to other antiretroviral drugs, 53% of patients attained HIV RNA suppression at undetectable levels. After 96 weeks, 60% of patients continued to exhibit HIV RNA suppression. 

The most frequent adverse effect was nausea. Severe side effects included elevated liver enzymes in those with comorbid hepatitis B or C and immune reconstitution syndrome, which is defined as an exaggerated inflammatory reaction to a disease-causing microorganism that can occur when the immune system is recovering following antiretroviral treatment.

The drug is contraindicated in those with previous hypersensitivity to fostemsavir or when taken with drugs that induce cytochrome P450(CYP)3A (eg, carbamazepine, phenytoin, rifampin, and St. John’s wort), which may lead to increased metabolism that limits virologic response 

Jeff Murray, MD, deputy director of CDER’s Division of Antivirals, highlighted the importance of the drug: “This approval marks a new class of antiretroviral medications that may benefit patients who have run out of HIV treatment options. The availability of new classes of antiretroviral drugs is critical for heavily treatment-experienced patients living with multidrug-resistant HIV infection—helping people living with hard-to-treat HIV who are at greater risk for HIV-related complications, to potentially live longer, healthier lives.” 

Trodelvy (acituzumab govitecan-hziy) for breast cancer

Treating triple-negative breast cancer is tricky because it lacks receptors for estrogen, progesterone, and human epidermal growth factor (HER2) that could serve as drug targets. Consequently, any therapeutic advance for this inimical condition is welcome.

The FDA fast-tracked the approval of Trodelvy, a biologic drug for adults with metastatic triple-negative breast cancer who received at least two prior therapies for metastatic disease. 

In a multicenter, single-arm trial involving 108 patients, participants received the drug intravenously in 21-day cycles until disease progression or intolerance of therapy, with imaging conducted every 8 weeks. The primary endpoints were overall response rate and response duration, which were 33.3% and 7.2 months, respectively.

Nausea, neutropenia, fatigue, diarrhea, anemia, alopecia, vomiting, rash, constipation, anorexia, and abdominal pain occurred in more than a quarter of participants. The drug can also lead to severe neutropenia and diarrhea. This biologic is contraindicated in those with severe hypersensitivity to it.

Tabrecta (capmatinib) for lung cancer

This kinase inhibitor was approved to treat metastatic non-small cell lung cancer (NSCLC) and is the first to target specific mutations in this disease—notably, those mutations that lead to mesenchymal-epithelial transition (MET) exon 14 skipping. Importantly, a companion diagnostic assay was also approved.

In the clinical trial, patients received 400 mg of capmatinib twice daily until disease progression or unacceptable toxicity. The primary endpoint was ORR, with duration of response also measured. In 28 treatment-naïve patients, the ORR was 68%, with 4% experiencing complete response and 64% having a partial response. In 69 previously treated patients, the ORR was 41%—all partial response.

In those who had never received treatment for NSCLC, 47% experienced a duration of response more than 12 months compared with 32.1% in those who were previously treated.

Common side effects included edema, fatigue, nausea/vomiting, dyspnea, and reduced appetite. Serious side effects included interstitial lung disease or pneumonia, as well as hepatotoxicity, which warrants monitoring of liver enzymes. The drug may also cause phototoxicity, so vigilant skin covering and sunscreen use are a good idea. Lastly, the drug is likely a teratogen, and even men taking the drug should use contraception as needed. The drug has no contraindications.

In an FDA release, Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence and acting director of the CDER’s Office of Oncologic Diseases, surveyed the landscape for cancer drug development in light of current events.

“In the face of the COVID-19 pandemic, our regular work on reviewing treatments for patients with cancer is moving forward,” he said. “The impact may be hardest on those with acute or chronic medical conditions and those with weakened immune systems, such as that caused by cancer and some forms of cancer treatment. We are working to address critical issues for patients with cancer and their healthcare providers and continuing to expedite oncology product development in this critical time.”

Tauvid (flortaucipir F18) for diagnosing Alzheimer disease

Specialists are much closer to a definitive diagnostic assessment of Alzheimer disease with the approval of Tauvid, a radioactive diagnostic drug used to tag the density and distribution of aggregated tau neurofibrillary tangles (NFTs) in patients with cognitive impairment. The drug is injected intravenously before positron emission tomography (PET) imaging.

“Alzheimer’s disease is a devastating condition that affects millions of Americans. This approval will provide healthcare professionals with a new type of brain scan to use in patients being evaluated for Alzheimer’s disease,” stated Charles Ganley, MD, director of the CDER’s Office of Specialty Medicine.

He added: “While there are FDA-approved imaging drugs for amyloid pathology, this is the first drug approved for imaging tau pathology, one of the two neuropathological hallmarks of Alzheimer's disease, and represents a major advance for patients with cognitive impairment being evaluated for the condition.”

Based on a postmortem study of 156 terminally ill patients—most with severe dementia—the researchers found that evaluators had a high probability of successfully identifying tau pathology when flortaucipir F18 was used. A second study was done to determine reader agreement, which was high in all patients. 

Adverse effects included injection site pain, headache, and elevated blood pressure. This drug is not indicated for use in patients with chronic traumatic encephalopathy.

Sarclisa (isatuximab-irfc) for multiple myeloma

Multiple myeloma is a blood cancer affecting plasma cells, which results in compromised immunity and bone/kidney problems. The National Cancer Institute predicts 32,370 new cases and 12,830 multiple myeloma deaths will occur in the United States in 2020. 

The FDA approved the drug, in combination with pomalidomide and dexamethasone, for the treatment of patients with multiple myeloma who have received at least two prior therapies, including lenalidomide and a proteasome inhibitor. This CD38-directed cytolytic antibody empowers the immune system to attack multiple myeloma cancer cells.

FDA approval of Sarclisa was based on a clinical trial that included 307 patients with relapsed/refractory multiple myeloma who had failed two prior therapies. Half of the patients in the trial were administered isatuximab-irfc plus pomalidomide and low-dose dexamethasone, while the other half received only pomalidomide and low-dose dexamethasone.

Those receiving the experimental agent had a 40% lower risk of disease progression or death. Furthermore, the ORR in the experimental group was 60.4% compared with that of 35.3% in the control group.

Frequent side effects of the drug include neutropenia, pneumonia, infusion-related reactions, upper respiratory tract infection, anemia, diarrhea, lymphopenia, and thrombocytopenia. Neutropenia can be severe, thus blood counts should be monitored. Clinicians should also be on the lookout for IV infusion-related reactions as well as second primary malignancies, a higher frequency of which were observed in patients taking isatuximab-irfc during clinical trials.

Interestingly, this drug may also interfere with certain blood assays, including antibody screening for blood transfusion as well as M-protein monitoring, which is used to assess complete response. So, patients should be typed and screened before starting therapy.

As is the case with other biologics, isatuximab-irfc is contraindicated in patients with severe hypersensitivity to it.

“Targeting cells has led to the development of important oncology treatments,” said Dr. Pazdur in an FDA release. “While there is no cure for multiple myeloma, Sarclisa is now another CD38-directed treatment option added to the list of FDA-approved treatments of patients with multiple myeloma who have progressive disease after previous therapies.”