Between 2009 and 2018, the FDA approved 355 drugs—including biologics. As imagined, research and development costs for these new drugs are astronomical. In a recent JAMA study, researchers examined expenditures for 63 of these 355 new approvals and found the median cost to bring a new drug to market was $985 million—including money spent on failed trials—with an average investment of $1.3  billion. Median prices ranged from $766 million for nervous system agents to $2.8 billion for antineoplastic and immunomodulating agents. Despite their high price tags, new drugs continue to roll out, with the pandemic failing to put a dent in approvals. Here are five new drugs approved in 2021 that you may find useful in your clinical practice of medicine.

Vericiguat

The FDA has approved vericiguat (VERQUVO) to decrease the risk of cardiovascular death and subsequent heart failure hospitalisation (following prior heart failure hospitalisation), or to reduce the need for outpatient IV diuretics in adults who have symptomatic chronic heart failure plus ejection fraction of 45% or less, according to a recent press release. Approval was based on results from the VICTORIA trial.

The primary outcome of the trial was whether vericiguat combined with other heart-failure treatments was superior to placebo plus other heart-failure treatments in lowering the risk of cardiac failure or heart failure hospitalisation in patients with the aforementioned indications. In these participants, there was a 4.2% decrease in annualised absolute risk with the drug vs placebo. The number of patients needed to treat over 1 year to prevent one primary outcome was 24 patients.

“Patients with symptomatic chronic heart failure and reduced ejection fraction have a high risk for hospitalisation after experiencing symptoms of heart failure requiring outpatient IV diuretic treatment or hospitalisation. By some estimates, more than half of these patients are rehospitalised within a month of discharge due to a worsening event and approximately one in five die within two years,” said Paul W. Armstrong, MD, who chaired the VICTORIA trial, in the release. “The approval of VERQUVO provides doctors, health care professionals, and patients with a welcome new option to current available therapies.”

Tepotinib

The drug tepotinib (Tepmetko) was approved for adult patients with metastatic non-small cell lung cancer (NSCLC) exhibiting mesenchymal-epithelial transition (MET) exon 14 skipping alterations.

Approval was based on results from the VISION trial (n=152), with the primary outcome being overall response rate (ORR). The ORR was 43% (95% CI: 33%-55%) with a median response duration of 11.1 months (95% CI: 9.5-18.5) in 83 previously treated patients. In 69 treatment-naïve patients, the ORR was 43% (95% CI: 32%-56%) with a median response duration of 10.8 months (95% CI: 6.9-not estimable).

Adverse reactions that occurred in 20% or more patients included edema, fatigue, nausea, diarrhea, musculoskeletal pain, and dyspnea. Importantly, this drug can also result in interstitial lung disease and hepatotoxicity, in addition to being a teratogen.

Cabotegravir 

The FDA fast-tracked the approval of cabotegravir and rilpivirine injection (Cabenuva) for the treatment of HIV in adults currently taking antiretrovirals. The drug is big news because it is the first FDA-approved injectable, complete treatment for HIV patients and is administered only once per month. Patients must be virologically suppressed on a stable antiretroviral regimen with no history of treatment failure and no resistance to cabotegravir or rilpivirine.

Cabenuva was deemed safe and effective based on two randomised, open-label, controlled clinical trials involving 1,182 HIV-infected adults who were virologically suppressed (HIV-1 RNA less than 50 copies/milliliter) before starting Cabenuva. Patients continued to demonstrate virologic suppression at the end of each trial, with no significant change in CD4+ cell counts.

In addition to site reactions, other adverse reactions include site reactions, dizziness, fatigue, fever, headache, musculoskeletal pain, nausea, rash, and sleep disorders.

“Currently, the standard of care for patients with HIV includes patients taking daily pills to adequately manage their condition. This approval will allow some patients the option of receiving once-monthly injections in lieu of a daily oral treatment regimen,” said the FDA’s John Farley, MD, MPH, in a press release. “Having this treatment available for some patients provides an alternative for managing this chronic condition.”

Lupkynis

Lupkynis (voclosporin) capsules are indicated in patients with active lupus nephritis and taken twice daily with mycophenolate mofetil and corticosteroid. 

In two clinical trials, researchers administered the drug to 533 patients with lupus nephritis in scores of clinical sites worldwide. They observed decreased kidney inflammation in patients taking the drug for one year compared with those taking placebo.

According to the FDA, “Lupkynis may cause serious side effects including increased risk of developing cancer, infection, kidney toxicity, high blood pressure, nervous system problems, high potassium, heart rhythm problems due to prolongation of heart electrical activity (QT prolongation), and low red blood cell count (anemia). The most common side effects are kidney toxicity, high blood pressure, diarrhea, headache, anemia, cough, and urinary tract infection.”

Lisocabtagene maraleucel

Gene therapy for the treatment of blood, bone marrow, and lymph node cancers is on a recent tear.

The FDA approved lisocabtagene maraleucel (Breyanzi) suspension for intravenous Infusion in adult patients with certain types of large B-cell lymphoma who have relapsed on, or not responded to, two or more systemic treatments.

This chimeric antigen receptor (CAR) T cell therapy is the third gene therapy that the FDA has approved for forms of non-Hodgkin lymphoma, including diffuse large B-cell lymphoma (DLBCL). Importantly, this biologic is not indicated to treat those with primary central nervous system lymphoma.

In clinical trials, this drug resulted in 54% complete remission in more than 250 adults with refractory or relapsed large B-cell lymphoma.

Doses of the drug are customised using a patient’s own T cells, which are collected and modified to target and kill lymphoma cells. 

The FDA issues specific caution regarding lisocabtagene maraleucel.

“Because of the risk of CRS [cytokine release syndrome] and neurologic toxicities, Breyanzi is being approved with a risk evaluation and mitigation strategy (REMS) which includes elements to assure safe use (ETASU). The FDA is requiring, among other things, that healthcare facilities that dispense Breyanzi be specially certified. As part of that certification, staff involved in the prescribing, dispensing or administering of Breyanzi are required to be trained to recognise and manage the risks of CRS and neurologic toxicities. The REMS program specifies that patients be informed of the signs and symptoms of CRS and neurological toxicities following infusion – and of the importance of promptly returning to the treatment site if they develop fever or other adverse reactions after receiving treatment with Breyanzi.”

This story is contributed by Alistair Gardiner and is a part of our Global Content Initiative, where we feature selected stories from our Global network which we believe would be most useful and informative to our doctor members.