Cancer’s Reign Over the Drug Development Pipeline Continues| AMCP Nexus 2024

There have exceptions to their rule, such as glucagon-like peptide 1 (GLP-1) drugs and the COVID-19 vaccines. But drugs to treat cancer have been the dominant force in pharmaceutical innovation, clinical trials and drug expenditures for many years now, and nothing in Kaelyn C. Boss’ oncology drug pipeline talk yesterday at the 2024 Academy of Managed Care Pharmacy (AMCP) Nexus meeting suggested that is going to change any time soon.

Kaelyn C. Boss, Pharm.D.

Oncology represents a large portion of the drugs in development, with approximately 1,600 medicines and vaccines in the pipeline, Boss, a clinical consultant pharmacist at UMass Chan Medical School in Worcester, Massachusetts, told the AMCP Nexus audience. A large percentage of the cancer-fighting agents are treatments for rare cancers with a relatively small number of suitable patients, Boss said, while also noting that there are also a large number of agents in development for solid tumors that affect many more people, she noted.

Boss said that spending on cancer drugs worldwide is projected to increase to $409 billion by 2028. The price of novel agents is high at more than $200,000 per year on average. She said that biosimilars and generic medications may yield savings, but the money saved is no match for new agents and the trajectory of higher spending.

Boss’ encyclopedic overview of oncology drug development included drugs that the FDA has approved this year, some of which were for new indications of previously approved drugs that had been previously approved, as well those still in the wings, with FDA action expected later this year or in early 2025.

Sita Bhatt, Pharm.D., a clinical pharmacy specialist at Boston Medical Center, joined Boss in making a presentation during the oncology pipeline session. She spoke about the growing number of cell therapies for solid tumors, a group that that includes LN-145-S1 for head and neck squamous cell carcinoma (HNSCC) and melanoma; LN-145 Gen 3 for HNSCC, melanoma and NSCLC; letetresgene autoleucel for soft tissue sarcoma; ECT240 for liver cancer; ET140203 for liver cancer; and CARv3-TEAM-E for glioblastoma.

“We can see a shift towards cell therapies for solid tumors,” Bhatt said. “44% of all trials initiated in 2023 [were] for solid tumor indications . . . this is really where we're seeing the trend in the oncology pathology space right now.”

Here are the cancer drugs that Boss discussed that have been approved by the FDA this year.

• Itovebi (inavolisib), a PI3K inhibitor for HER2-negative breast cancer with a PIK3CA mutation, was also approved on Oct. 10. It was studied in combination with fulvestrant and palbociclib following progression on at least one endocrine-based regimen or within 12 months of adjuvant therapy. It is also being studied in combination with fulvestrant for HR+/HER2- breast cancer and in combination with dual HER2 blockade and endocrine therapy.
• Tecentriq Hybreza (atezolizumab and hyaluronidase-tqjs) is a PDL-1 inhibitor that was approved on Sept. 12. for multiple indications, including nonsmall cell lung cancer (NSCLC). It is formulation of Tecentriq that will allow for subcutaneous administration. Tecentriq was orginally approved in 2016.
• The combination of Lazcluze (lazertinib) and Rybrevant (amivantamab) was approved on Aug. 19 as a first-line treatment NSCLC with epidermal growth factor receptor (EGFR) mutations.
• Niktimvo (axatilimab) is an anti-CSF-1R antibody approved for chronic graph versus host disease (GVHD) on Aug. 14.
• Lymphir (denileukin diftitox-cxdl) is an IL2-receptor-directed cytotoxin approved on Aug. 7, for relapsed or refractory cutaneous T-cell lymphoma. The drug is a reformulated version of Ontak (denileukin diftitox), which was withdrawn due to manufacturing errors. National Comprehensive Cancer Network guidelines recommend the drug as preferred for stage 2B mycosis fungoides with generalized tumor disease and useful for some situations with other stages of mycosis fungoides with limited tumor disease.
• Voranigo (vorasidenib) is an IDH1 and IDH2 inhibitor that was approved on Aug. 6 for treatment of grade 2 IDH-mutant glioma. The drug is also being studied in combination with Keytruda (pembrolizumab0 for recurrent or persistent IDH-1 astrocytomas. Of note, the cost per 40 mg tablet is $1,329 and $29,881 per 30 count bottle.
• Tecelra (afamitresgene autoleucel) is a MAGE-A4-directed genetically modified autologous T-cell immunotherapy that received accelerated approval on Aug. 2 a as treatment for unresectable or metastatic synovial sarcoma. It is one-time intravenous therapy that modifies T cells to attack cancer cells. The drug was launched with a list price of $727,000.
• Augtyro (repotrectinib) is a kinase inhibitor that was granted accelerated approval on June 13 as a treatment for solid tumors with a neurotrophic tyrosine receptor kinase gene fusion that are locally advanced or metastatic, positive solid tumors. It had been previously approved in November 2023, as treatment for locally advanced or metastatic ROS1-positive NSCLC. The estimated cost per 120 count of the drug is $14,500.
• Rytelo (imetelstat) is an oligonucleotide telomerase inhibitor that received approval on June 6 as a treatment for low- to intermediate-1 risk myelodysplastic syndrome (MDS) with transfusion dependent anemia. Rytelo is priced to cost approximately $385,000 a year (based on a patient weighing 70 kg), which is almost four times more than an Institute for Clinical and Economic Review assessment said it should cost based on common cost-effectiveness thresholds.
• Imdelltra (tarlatamab-dlle) received accelerated approval on May 16 as a bispecific T-cell engager for extensive stage small cell lung cancer. The estimated cost of the drug is $15,000 per 10 mg, $31,500 for cycle one and step-up dosing, and $30,000 for cycle 2 and beyond. According to NCCN recommendations, Imdelltra is preferred for small cell lung cancer as subsequent systemic therapy in chemotherapy free intervals of 6 months or less.
• Ojemda (tovorafenib)accelerated approval on April 23 as a Pan-RAF kinase inhibitor for relapsed or refractory pediatric low-grade glioma with BRAF fusion or rearrangement, or BRAF V600 mutation. The estimated cost per 16, 20 or 24 count bottle is $33,916 and $8,479 per 12 mL bottle. The drug is also being studied in combination with nivolumab for the treatment of craniopharyngioma.
• Anktiva (nogapendekin alfa inbakicept-pmln) received approval on April 22 as an IL-15 receptor agonist for Bacillus Calmette-Guérin-unresponsive, nonmuscle-invasive bladder cancer. The cost of induction is estimated at $214,800 and patients can receive up to two courses. For maintenance therapy at month four to 19, the estimated cost is $537,000 and an estimated $322,200 for months 25 to 27. The maximum total course for the full 27 months, including two induction courses, is estimated to be $1,288,800.
• Tevimbra (tislelizumab-jsgr) is a PD-1 inhibitor, which was approved on March 13 for unresectable or metastatic esophageal squamous cell carcinoma. The NCCN recommends the drug in the second-line or subsequent therapies for category one. The cost per 10 mL (100 mg) and per dose (200 mg) is approximately $5,204 an $10,408, respectively.
• Amtagvi (lifileucel) received accelerated approval on Feb. 16 for unresectable or metastatic melanoma as a tumor-derived autologous T cell immunotherapy. The drug is recommended by the NCCN as a preferred tumor-infiltrating lymphocyte therapy.

And here are the cancer drugs mentioned by Boss that are likely to be coming up for FDA approval decisions soon.

• A decision on zenocutuzumab, a bispecific antibody for NRG1-positive NSCLC and NRG1-positive pancreatic cancer, is expected in the fourth quarter of 2024. It has also been given fast track designation by the FDA.
• A decision on zolbetuximab, a CLDN18.2-targeted antibody for HER2-negative, CLDN18.2-positive locally advanced unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma, is expected on Nov. 9.
• A decision on obecabtegene autoleucel, a CAR-T therapy for relapsed or refractory adult B-cell acute lymphoblastic leukemia, is expected on Nov.16. If the FDA approves it,obecabtegene autoleucelwould be the third CAR-T cell for this disease.
• A decision on zanidatamab, a HER2-targeted bispecific antibody for previously treated, unresectable, locally advanced, or metastatic HER2-amplified biliary tract cancer, is expected on Nov. 29.
• Decisions on datopotamab deruxtecan, an antibody drug conjugate for advanced nonsquamous NSCLC and metastatic HR-positive, HER2-negative breast cancer, are expected on Dec.20 and Jan. 29, 2025, respectively.
• A decision on revumenib, a menin-KMT2A inhibitor for relapsed or refractory KMT2Ar acute leukemia, is expected on Dec. 26. If it gets the FDA’s OK, revumenib would be the first menin inhibitor approved. Other menin inhibitors in development are either in phase 2 (ziftomenib) or phase 1 trials (JNJ-75276617, DSP-5336, BMF-219, BN104, and balamenib.)
• A decision on cosibelimab, a PD-L1 inhibitor, is expected on metastatic or locally advanced cutaneous squamous cell carcinoma, on Dec. 28. In December 2023, the FDA issued a complete response letter for the drug, and it was resubmitted in July 2024.
• A decision on ensartinib, an ALK inhibitor for ALK-positive NSCLC, is expected on Dec. 28. The drug is also being studied for pediatric patients with solid tumors, non-Hodgkin lymphoma, or histiocytic disorders with ALK or ROS1 genomic alterations that are recurrent or relapsed.
• A decision for the subcutaneous formulation of Opdivo (nivolumab), a PD-1 inhibitor for many oncology indications, is expected on December 29, 2024.
• A decision for mirdametinib, a MEK inhibitor for neurofibromatosis type 1-associated plexiform neurofibromas, is expected in the first quarter of 2025. It has been granted orphan drug designation by the FDA and the European Commission. It is also being studied in combination with lifrafenib for advanced or refractory solid tumors.
• A decision for remestemcel-L, a stem cell therapy for acute GVHD, is expected on January 7, 2024. The drug was issued two CRLs, with one due to lack of potency data and one for additional data on highest risk population.
• A decision on tabelecleucel, an allogenic T-cell immunotherapy for Epstein-Barr virus-positive post-transplant lymphoproliferative disease, on Jan. 15, 2025.
• A decision for the subcutaneous formulation of Rybrevant (amivantamab), a bispecific antibody for NSCLC, is expected in the second quarter of 2025.