Growing Innovation, Cost Expected in the Oncology Drug Pipeline

Oncology represents more than a third of specialty drugs in the pipeline with substantial growth seen in recent years for clinical development and accelerated approvals. But rising cost of these new and emerging therapeutics continues to have major implications for managed care stakeholders, according to experts of the concluding keynote session on Friday at the Academy of Managed Care Pharmacy (AMCP) Nexus 2022 meeting.

As a standalone session from AMCP’s annual specialty drug pipeline, oncology drugs currently dominate the medical benefit spend. Oncology revenue in 2019 was $103.5 billion, said Kaelyn C. Boss, PharmD, clinical consultant pharmacist, Commonwealth Medicine University of Massachusetts Medical School, who added that this market continues to grow as novel agents are coming to market faster through accelerated approvals.

Amongst cancer types with the greatest number of agents and treatment strategies in development, excluding unspecified solid tumors, Boss highlighted lung, leukemia, lymphoma, and breast cancer as the main areas of innovation. Last year exhibited a record number of approvals in oncology with 56, and 2022 has shown 17 approvals and counting, including for biosimilars.

“With all these approvals, we’re seeing an upward trend of launches for novel active substances globally,” she added.

Regarding recently approved and emerging oncology specialty drugs, Boss said that bispecific anitbodies, small molecules, checkpoint inhibitors, and cell therapies show notable potential for growth in the near future.

Notable drugs either approved or in development within these class of therapies include:

• Bispecific antibodies: tebentafusp-tebn (first FDA approved drug in uveal melanoma) and teclistamab (multiple myeloma [MM])
• Checkpoint inhibitors: pembrolizumab (approved for 18 cancer types), nivolumab (approved for 11 cancer types), tislelizumab (being studied for 6 cancer types), tremelimumab (in combination with durvalumab for hepatocellular carcinoma), and combination therapy of nivolumab and relatlimab-rmbw (melanoma)
• Cell therapies: ciltacabtagene autoleucel (MM), idecabtagene vicleucel (MM), tabelecleucel (Epstein-Barr virus positive post-transplant lymphoproliferative disease), and afamitresgene autoleucel (advanced synovial sarcoma or myxoid/round cell liposarcoma)
• Small molecules: poziotinib (non-small cell lung cancer [NSCLC]), adagrasib (NSCLC; being studied in other KRAS G12C mutated cancers), mobocertinib (EGFR Exon 20 in NSCLC), futibatinib (cholangiocarcinoma [CCA] with FGFR2 gene fusion/rearrangement), and elacestrant (estrogen receptor-positive, HER2 negative breast cancer)
  

Bhavesh Shah, RPh, BCOP, chief pharmacy officer and director of specialty and hematology/oncology pharmacy at Boston Medical Center, delved further into future emerging oncology pipeline trends and their evolving impact on the treatment landscape as it pertains to managed care providers.

Tumor-Agnostic Therapy

Approved and emerging tumor-agnostic therapies in the pipeline, such as BRAF inhibitors, programmed cell death protein-1 (PD-1) agents, and neurotrophic tyrosine receptor kinase (NTRK) inhibitors, have increased treatment options for patients with several different cancers.

KRAS mutations, which Shah noted to be an “undruggable” target for more than 40 years, now has an FDA approved therapy in sotorasib and adagrasib has also shown potential in NSCLC and other KRAS G12C mutated cancers.

However, the benefits from these therapies are not always similar across multiple tumors or patients, said Shah, who added that disparities exist regarding access to biomarker testing (next-generation sequencing [NGS]), as well as challenges to obtaining sufficient tissues for these tests.

“Working in oncology, we see a lot of providers doing NGS testing, but just because a patient has the mutation doesn't mean that you can actually use whatever drugs approved unless you actually have the data,” he said. “There’s been more push from the FDA that we’re not just going to approve these agents based on response rates, but also to look at overall survival and progression-free survival benefit with these therapies.”

Checkpoint Inhibitors

From a payer and provider perspective, checkpoint inhibitors are the biggest item on your budget line, noted Shah, with PD-1 and programmed death ligand-1 (PD-L1) inhibitors estimated to generate $58 billion in market revenue by 2025.

In looking at the landscape of PD-1/PD-L1 inhibitors, more than 20 of these drugs have been approved and several others are coming to market. PD-1/PD-L1 “disruptors” have also garnered controversy, with a majority only having trials conducted in China, raising concerns among the FDA and local regulators on the generalizability of these medications in the United States. These disruptors could also increase development costs and timelines for new entrants, noted Shah.

“The biggest indication where PD-1s really would slow the market is NSCLC—that is 80% of your utilization for any PD-(L)1,” he said.

Potential combination therapy being investigated in phase 3 studies that would impede new PD-1 agent disruption included tiragolumab, vibostolimab, domvanalimab, and ociperlimab.

“If these combination therapies get approved, what does that mean for PD-1 disruptors? Obviously, they become obsolete. Because now you can actually change the standard of care from just PD-1 plus the chemotherapy to PD-1 and TIGIT,” explained Shah.

Amid the potential launch of these PD-(L)1 disruptors, he added that providers should monitor this evolving pipeline and consider starting discussions with manufacturers with early commitment to value-based contracting.

Hematologic Malignancy High Impact Pipeline Agents

Chimeric antigen receptor (CAR) T-cell therapy, particularly B cell maturation antigen (BCMA)-targeted drugs, have shown significant promise in the management of MM, said Shah, with several clinical trials approaching their completion date by next year (KarMMa-2/3 and CARTITUDE-2).

“Currently, these drugs are approved in fourth line and beyond but soon there will be data for second line plus…I would like to point out that we haven't actually scratched the surface of CAR—we have a C19 and BCMA, but there are multiple other CARs are in the pipeline, so we'll be seeing more CAR therapies.’

Bispecific BCMAs such as teclistamab are also noteworthy as they are not as burdened by manufacturing issues as CAR-T cell therapies and have better availability as well (“off the shelf”). However, they may require hospitalization for the first dosage and are similarly challenged by toxicities (cytokine release syndrome).

Major cost considerations were addressed as well with unknowns related to cost for bispecific BCMAs and $419,000 to $465,000 one-time cost estimated for BCMA CAR-T cell therapy.

Radiopharmaceuticals

Improvements in treatment access were further discussed regarding prostate cancer, with newer technologies enabling therapeutic radiopharmaceuticals to reach more patients.

Approved (radium-223 dichloride and lutetium-177 vipivotide) and emerging radiopharmaceuticals (lutetium-177-radiohybrid prostate-specific membrane antigen (rhPSMA) 10.1 and lutetium-177 PSMA I&T) are in the prostate cancer pipeline with over 1400 outpatient locations in the United States providing these drugs.

As radiopharmaceuticals continue to be investigated in the first-line and second-line, Shah cautioned that providers will require larger generators to keep up with demand as there remains significant limitations in manufacturing access.

“Imagine the patient who actually starts on this, gets a fixed duration, and doesn’t have to get any hormonal therapy.”

CD47 Immune Checkpoint Inhibitors

The last trend mentioned by Shah in the oncology drug pipeline was CD47 immune checkpoint inhibitors, which show potential in many hematologic and solid tumors. High CD47 expression is known to correlate with aggressive disease and poor outcomes and applying CD47 blockade prevents CD47 attachment to macrophage phagocytosis, he explained.

The current pipeline of CD47 immune checkpoint inhibitors included PF-07901801 (formerly TTI-622), magrolimab, ALX148, lemzoparlimab, AO-176, TG-1801, and PF07257876.

These drugs are likely to first launch in myeloid malignancies (myelodysplastic syndromes and acute myeloid leukemia), with the development of future bifunctional agents targeting solid tumors (PD1/CD47) and hematologic malignancies (CD19/CD47) potentially expanding their reach. Other managed care implications referenced by Shah in the CD47 pipeline were for providers to consider strategies with optimal agents selection to mitigate off-target toxicities (anemia/thrombocytopenia).