Oncology Pipeline Overview: Recent Approvals and Near-Term Drugs

Many innovative therapies in oncology have made it to market recently, with a wealth of agents that are currently on the verge of FDA approval. At the 11th Annual Summit of the Association for Value-Based Cancer Care in 2021, a panel of oncology drugs experts moderated by Doug Long, MBA, Vice President of Industry Relations, IQVIA, discussed current pharmaceutical trends in oncology drug development, including recent FDA approvals and near-term innovative agents coming to market in the near future.

The US oncology therapeutics market has reached $71 billion, according to Mr Long. Although COVID-19 has slowed the growth of drug sales, the total growth in the oncology market is being driven by the targeted drugs in oncology, he emphasized. COVID-19 has not had an impact on the number of launches in the oncology space, he said, as 2020 and 2021 have seen similar rates of drug launches as was seen in 2019.

Dipti Shah, PharmD, CSP, Senior Clinical Program Manager, CVS Specialty, Northbrook, IL, provided an overview of the oncology drug landscape, highlighting a handful of especially innovative pharmaceuticals, some in niche areas.

Recently Approved Cancer Drugs

In 2021, tivozanib (Fotivda) received FDA approval for the treatment of patients with relapsed or refractory renal-cell carcinoma. Although an improvement in progression-free survival was demonstrated with tivozanib compared with sorafenib (Nexavar) in patients with advanced disease, overall survival data favored sorafenib, she observed.

Umbralisib (Ukoniq) was granted FDA approval for the treatment of patients with marginal zone lymphoma. Approximately 7500 patients annually are diagnosed with this disease. “An additional therapy in this space is going to give patients choice, especially with its good side-effect profile in clinical trials,” Dr Shah said.

Tepotinib (Tepmetko) gained approval for the treatment of metastatic non–small-cell lung cancer (NSCLC) harboring MET exon 14 skipping alterations. Only approximately 3% to 4% of patients with NSCLC have such alterations, but their prognosis is poor, she said.

Lisocabtagene maraleucel (Breyanzi) is a CAR T-cell genetically modified therapy that was approved by the FDA for the treatment of patients with relapsed or refractory large B-cell lymphoma. In the single-arm, open-label TRANSCEND clinical trial conducted in patients with relapsed or refractory disease, the overall response rate with lisocabtagene maraleucel was 73%. Of the 104 patients who had a complete response, 65% had remission lasting ≥6 months, and 62% had remission lasting ≥9 months.

The 10-year follow-up of these patients will be very important, and will ultimately be the driver of value behind these therapies, said panelist Cheryl Allen, PharmD, Executive Vice President, Business Development, Specialty Pharmacy Nursing Network, Sarasota, FL.

Sotorasib (Lumakras) is an oral therapy that targets the KRAS gene; it is the first drug to receive FDA approval for any malignancy associated with KRAS; it was approved for the treatment of patients with KRASG12C-mutated NSCLC. “It is important to note that KRAS has multiple biomarkers within itself,” said Dr Shah. “Only those patients with a KRASG12C mutation will respond to this therapy.” This type of mutation represents less than 3% of patients with NSCLC, she noted.

Mobocertinib (Exkivity) is an oral tyrosine kinase inhibitor that was approved for the treatment of metastatic NSCLC and EGFR exon 20 insertion mutation. These mutations occur in 4% to 12% of patients with NSCLC and EGFR mutation, and approximately 2% of all patients with NSCLC.

The Near-Term Drug Pipeline

Dr Shah highlighted 3 novel therapies in oncology that are expected to gain FDA approval before the end of 2021 or in 2022—pacritinib, ublituximab, and magrolimab—as well as the immunotherapy nivolumab (Opdivo), which is expected to receive yet another new indication in the near future.

Pacritinib is an oral macrocyclic Janus kinase (JAK) inhibitor that is being developed for the treatment of myelofibrosis and may represent a good option in patients with severe thrombocytopenia, Dr Shah said. Its unique mechanism of action, inhibiting JAK2 and IRAK1 without inhibiting JAK1, may reduce the risk for cytopenias and immune dysfunction associated with other JAK inhibitors. It was granted a priority review by the FDA in June 2021 with an original Prescription Drug User Fee Act action date of November 30, 2021. However, this date has now been extended to February 28, 2022.

A biologics license application was accepted by the FDA for the CD20-directed monoclonal antibody ublituximab (to be used in combination with umbralisib) for the treatment of patients with chronic lymphocytic leukemia or with small lymphocytic lymphoma. Expected approval is March 25, 2022.

An application for the use of nivolumab in combination with ipilimumab (Yervoy) or with chemotherapy in the first-line setting for patients with unresectable advanced, recurrent, or metastatic esophageal squamous-cell carcinoma was accepted by the FDA. This application was based on results from the pivotal phase 3 CheckMate-648 clinical trial, in which the combination of nivolumab plus ipilimumab and nivolumab plus chemotherapy demonstrated a statistically significant and clinically meaningful benefit in overall survival compared with chemotherapy in patients with unresectable, advanced or metastatic esophageal squamous-cell carcinoma associated with PD-L1 expression of ≥1%, as well as in the all-randomized population. FDA approval is expected on May 28, 2022.

Magrolimab is an anti-CD47 monoclonal antibody being studied in combination with azacitidine (Onureg; which was approved in 2021 for myelodysplastic syndrome) as first-line combination regimen for the treatment of patients with intermediate-, high-, or very high-risk myelodysplastic syndrome. In a phase 1b clinical trial, this combination showed a complete response of 42% versus 20% with azacitidine monotherapy. FDA approval is expected in the third quarter of 2022.

Unmet Need a Huge Burden

“Despite amazing new drugs, some patients aren’t benefiting sufficiently or at all. There’s still tremendous unmet need in oncology, which is why the huge pipeline of activity,” said Jeffrey Bockman, PhD, Executive Vice President, Oncology Practice Head, Cello Health BioConsulting, Florham Park, NJ. That oncology pipeline is filled with a plethora of non-immunotherapy agents, but immune-oncology and precision medicine are driving pipeline value, he said.

Clinical benefit—or value—not simply price, is becoming a focus even for early-stage drug developers, said Dr Bockman, especially so for multicomponent, high-priced immunotherapy regimens.

Dr Allen made a case for value-based oncology determinations with the increase in innovation.

Right now, much of the cost of therapy is the payers’ burden, she said, and the patient is generally not involved. Financial support from the manufacturer is usually limited to commercially insured patients. To make better decisions, with increasing competition in the oncology space, “head-to-head studies are needed to see what this will do ultimately for the payer base,” Dr Allen said.

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