Cancer Drug Pipeline Focused on Precision Treatments

The oncology drug pipeline is concentrated with therapies that take a precise approach to treating specific cancer types, according to an educational session at AMCP Nexus 2017.

During the presentation, Edward Li, PharmD, MPH, professor of pharmacy at the University of New England College of Pharmacy, highlighted three cancer treatments that are were likely to gain FDA approval in 2018. These drugs included Verzenio (abemaciclib; Eli Lilly) Calquence (acalabrutinib; AstraZeneca), and larotrectinib (Loxo Oncology). Since Dr Li’s presentation, both Verzenio and Calquence received FDA-approved indications for treating specific cancer patient subpopulations.

Dr Li began his presentation by explaining that the specialty drug distribution channel has grown significantly since 2011. He cited data showing that total spending on antineoplastic drugs—agents that target tumor gene mutations—increased from $26.8 billion in 2011 to $38.9 billion in 2016.

He also explained that the focus has shifted in the last 3 years toward immuno-oncology drugs. Dr Li showed a slide that demonstrated the increase in immune-oncology drug approvals since 2010, when Provenge (sipuleucel-t; Valeant) was first approved. He explained that a number of treatments are under investigation, including CAR-T gene therapy treatments, highlighting the wide range of opportunities presented by these types of therapies.

Dr Li also stressed that a number of other agents are also under investigation in the cancer therapy pipeline, including androgen pathways agents, tyrosine kinase inhibitors for specific mutations. CDK4/6 therapies, poly ADP-ribose polymerase inhibitors, and phosphatidylinositol 3-kinase therapies.

According to Dr Li’s presentation, oral cancer therapies have also increased in prevalence. He cited data showing that since 2003, spending on oral oncology treatments has increased from $1 billion to $6 billion in 2012. During the same timeframe, dispensing of oral agents through specialty pharmacies more than doubled, from 26% to 61%.

The Potential for Verzenio

Verzenio, a CDK4/6/9 inhibitor, was among the oral agents that Dr Li highlighted. Verzenio received FDA approval to treat certain advanced or metastatic breast cancers on September 28, 2017.

According to the FDA approval, Verzenio is most effective among patients with “hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer that has progressed after taking therapy that alters a patient’s hormones.” According to the presentation, the drug was approved for use with Faslodex (fulvestrant; AstraZeneca).

Dr Li highlighted that Verzenio inhibits CDK4, 6, and 9, but is significantly more selective for CDK4, with absorption through the blood-brain barrier. He noted that Verzenio can be used as a monotherapy, or can be administered with Faslodex. Dr Li stated that the Prescription Drug User Fee Act date for approval of Verzenio as a single-agent is January 10, 2018.

During the presentation, Dr Li reviewed clinical trial data from two studies, the MONARCH 1 and MONARCH 2 trials, that examined the efficacy of Verzenio. The studies enrolled women in last-stage cancer settings with endocrine-therapy-refractory disease. MONARCH 1 studied Verzenio as a single agent in a phase 2, single-arm, open-label, multicenter trial. While, MONARCH 2 studied Verzenio with Faslodex, in a phase 3, randomized, double-blind, placebo-controlled trial.

According to the presentation, although overall survival data is not yet available, Verzenio improved progression-free survival. He noted that Verzenio will be a second-line treatment after endocrine treatment failure, and will compete with Ibrance (palbociclib; Pfizer) in this drug space, offering a different side effect profile. According to Dr Li, Verzenio is intended for a very specific and smaller patient subpopulation: patients who received endocrine therapy and one or two chemotherapies who have also not been exposed to CDK4 and 6 inhibitors.

Dr Li stated that Verzenio will replace Ibrance to some degree, but will have low to moderate use as a single agent. He expects the drug to have only a moderate impact on pharmacy spending.

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The Impact of Calquence

Calquence, a second generation BTK inhibitor for patients with previously treated mantle cell lymphoma and relapsed chronic lymphocytic leukemia, was the second drug highlighted by Dr Li during his presentation. The treatment is a kinase inhibitor that functions by blocking an enzyme the cancer needs to multiply.

Dr Li explained that Calquence was developed to be more potent and selective than Imbruvica (ibrutinib; Janssen), thus reducing toxicities related to off-target effects. Dr Li noted that cell death  and chemokine inhibition between Calquence and Imbruvica were similar—however, Imbruvica produced more off-target effects on SRC-family kinases.

According to the October, 31 FDA approval of Calquence, the drug was approved for “ adults with mantle cell lymphoma who have received at least one prior therapy.”

“Mantle cell lymphoma is a particularly aggressive cancer,” Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research, said in a press release accompanying the approval. “For patients who have not responded to treatment or have relapsed, Calquence provides a new treatment option that has shown high rates of response for some patients in initial studies.”

Dr Li stated that the drug will serve a niche population of cancer patients, including patients with solid tumors taking Keytruda (pembrolizumab; Merck).

Predictions for Larotrectinib

The third drug highlighted by Dr Li was larotrectinib, an oral, selective TRK inhibitor. Dr Li explained that larotrectinib is highly potent against TRKA, TRKB, and TRKC proteins. He noted that the drug is 1000 times more selective than other off-target drugs in this space.

Dr Li stated that phase 2 trials are currently underway examining the effects of larotrectinib in a cohort of patients with NTRK fusion mutations and nervous system tumors. According to the presentation, larotrectinib will likely serve in this niche population of rare tumors.

FDA approval will be dependent on the five clinical trials currently underway for larotrectinib. Dr Li noted that only about 2% of tumors harbor these specific mutations; however there is an unmet need in these areas of treatment. He posited that if the trials go well, FDA approval should follow at the end of 2018.

Dr Li stated that the price for larotrectinib will likely be on the high end compared to similar oral therapies; however, he does not expect the therapy to have a large impact on overall spending due to the small potential patient population. He also stated that introduction of this treatment option to the market may increase the use of next-generation sequencing.

“Since all three agents are designated as breakthrough therapies, the data demonstrating their clinical utility is not yet mature,” Dr Li concluded. “The overall potential impact of these agents on overall oncology drug spending is expected to be low to moderate.”

—David Costill

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