Pharmaceutical pipeline: Top 4 conditions to watch

Drugs to treat inflammatory conditions, diabetes, and oncology were the top three most expensive therapy classes in 2016, according to Express Scripts. But there are some positive changes on the horizon.

Tharaldson“Managed care executives should be hopeful that new drugs pending approval in 2017 could increase competition within these classes. We are also keeping an eye on the pipeline of drugs to treat Alzheimer’s,” says Aimee Tharaldson, PharmD, senior clinical consultant, Emerging Therapeutics, Express Scripts.

Although the drug pipeline for Alzheimer’s disease has not been as rich as patients and experts would have hoped, there could be some form of a drug to combat this debilitating condition by 2025, CNN recently reported. With more than 20 candidates in phase 3 trials and many more in earlier stages of development, researchers are hopeful that this goal will be realized.

Here’s more on each of these drug classes, and what you can anticipate in the year ahead.

Autoimmune diseases

There are two key autoimmune pipeline developments to watch in 2017, according to Tharaldson. They are investigational baricitinib, a once-daily oral medication for the treatment of moderate-to-severe rheumatoid arthritis (RA), and guselkumab, an anti-interleukin-23 (IL-23) monoclonal antibody, for moderate-to-severe plaque psoriasis.

In April, the FDA delayed approval of baricitinib, an oral Janus kinase (JAK) inhibitor. The FDA said that more clinical data is needed because of safety concerns across treatment arms. Baricitinib is also being studied in phase 2 trials for atopic dermatitis and systemic lupus erythematosus, and a phase 3 trial for patients with psoriatic arthritis is expected to be initiated in 2017.

FDA said that more clinical data is needed because of safety concerns across treatment arms of the new investigational drug baricitinib (Eli Lilly and Company, Incyte Corporation). Additional clinical data is needed to determine the most appropriate doses, the two manufacturers said in a statement.

IL-23 is a protein which has been shown to play a key role in the development of immune-mediated inflammatory diseases.

Guselkumab in a subcutaneously administered IL-23 inhibitor in phase 3 development to treat moderate-to-severe plaque psoriasis.  At press time, a phase 2 study evaluating the drug for the treatment of moderately to severely active psoriatic arthritis was ongoing.

“Watch for more competition in this space due to an increasing number of therapeutic options,” Tharaldson says. “Biosimilars may also help to increase competition. Although biosimilars for Humira and Enbrel have been approved by the FDA, several biosimilar-related patent disputes have prevented their launch.”

Patrick Gleason, PharmD, FCCP, FAMCP, BCPS, senior director, health outcomes, Prime Therapeutics, says the PBM has identified Dupixent (dupilumab) as a new potential blockbuster drug for the treatment of atopic dermatitis. Dupixent is a self-administered subcutaneous injection, approved by the FDA in March. It is the first biologic to treat atopic dermatitis, a condition typically treated with topical moisturizers, corticosteroids, and calcineurin inhibitors. Dupixent works by inhibiting interleukin-4 and interleukin-13, two key cytokines required for certain immune responses.

Over the past four years, Prime has seen the autoimmune drug class spend increase 25% each year. Gleason expects this trend to continue due to price inflation and more patients using these specialty drugs more quickly when diagnosed.

Next: Diabetes

Diabetes

There are new diabetes medications to watch, according to Farrah Wong, PharmD, director, pipeline and drug surveillance, OptumRx. They include semaglutide, sotagliflozin, and insulin tregopil.

Semaglutide is a GLP-1 agonist in development for glycemic control in patients with type 2 diabetes. At press time, it was being developed as both subcutaneous (Novo Nordisk) and oral (Novartis) formulations. The subcutaneous formulation is under FDA review first and may be approved in December 2017. Oral semaglutide may become the first oral GLP-1 receptor agonist on the market, with the potential advantage of easier and less-invasive administration.

Sotagliflozin is a sodium-dependent glucose transporter (SGLT-1 and SLG-2) inhibitor in development for both type 1 and type 2 diabetes at press time. If approved (anticipated in the second half 2018), it would be the first oral drug approved for type 1 diabetes, a disease that typically has been managed by lifestyle modifications and insulins, according to Wong.

New insulin products may also be approved soon. Insulin tregopil is an oral insulin in phase 2 development for both type 1 and type 2 diabetes and has the potential to be the first oral insulin on the market, with anticipated approval to be in 2020. Basalog, an insulin glargine product, was in phase 3 development at press time. It is unknown whether manufacturer Mylan/Biocon will seek approval as a competing brand insulin or as a generic to Sanofi’s Lantus.

Also in the diabetes management armamentarium is Medtronic’s hybrid closed-loop system for patients with type 1 diabetes. The MiniMed 670G System, which was FDA approved in September 2016, features an advanced algorithm that automates and personalizes the delivery of basal insulin 24 hours a day to maintain glucose levels.

“The hybrid closed loop system requires minimal input, with patients only needing to enter mealtime carbohydrates, accept bolus correction recommendations, and periodically calibrate the sensor,” says Mike Hill, vice president of Global Marketing, Intensive Insulin Management, Medtronic. “With a fully automated closed loop system, Medtronic is working toward decreasing this interaction to further simplify diabetes management for patients with type 1 diabetes.”

Next: Oncology

Oncology

Rosier“Oncology continues to be a key area of focus for pharmaceutical manufacturers given the significant need for effective treatment options across a host of different types of cancer,” says Nadina Rosier, health and group benefits practice leader, pharmacy, Willis Towers Watson. “This year we are expecting at least 10 agents to be FDA approved for cancer indications, four of which are for breast cancer.”

These agents are oral all drugs and could cost at least $120,000 per patient per year, “placing significant pressure on healthcare executives to more aggressively manage the specialty pharmacy aspect of their medical and pharmacy benefit programs more tightly,” says Rosier.

Pipeline breast cancer therapies include abemaciclib, entinostat, and neratinib.

Lilly is seeking FDA approval for abemaciclib, a cyclin-dependent kinase-4 and cyclin-dependent kinse-6 inhibitor for refractory patients with hormone-receptor positive, human epidermal growth factor 2-negative (HER2) metastatic breast cancer. Approval is expected in the second half of 2017.

Abemaciclib is also being studied in non-small cell lung cancer (NSCLC).

Entinostat, an oral, small molecule histone deacetylase (HDAC) inhibitor, has direct effects on both cancer cells and immune regulatory cells, potentially enhancing the body’s immune response to tumors. Approval is anticipated this year with the proposed indication of treatment of postmenopausal women with advanced estrogen receptor-positive (ER+) breast

cancer who have progressed on a non-steroidal aromatase inhibitor.  If approved, it would be given orally once weekly in combination with exemestane. Entinostat is also in phase 2 development for NSCLC, non-Hodgkin’s lymphoma and ovarian cancer.

Neratinib is an oral, irreversible pan-ErbB receptor tyrosine kinase inhibitor in phase 3 development for the treatment of advanced breast cancer (including HER2+), as monotherapy and in combination with chemotherapy. At press time, approval of neratinib was expected in July 2017 for advanced breast cancer (including HER2+).

Unique approaches to overcoming tumor resistance is also being explored in the oncology space. “Certain cancers have been shown to accumulate high levels of hyaluronan [HA], a naturally occurring sugar in the body,” according to Helen Torley, president and CEO of biotechnology company Halozyme. “This accumulation creates a unique microenvironment that can foster the growth of tumor cells and create a barrier to drug delivery, inhibiting the potential effectiveness of many anti-cancer agents.”

Halozyme is seeking to target the tumor microenvironment with PEGPH20, its lead investigational drug currently being evaluated in multiple tumor types that accumulate high levels of HA, Torley says.

Earlier this year, Halozyme announced positive data from its phase 2 study, HALO-202, which evaluated PEGPH20 in combination with nap-paclitazel and gemcitabine in patients with advanced pancreatic cancer. Halozyme is partnering with other pharmaceutical companies to evaluate the pan tumor potential of PEGHP20 in combination with other therapies for the treatment of pancreatic, gastric and metastatic breast cancers.

Next: Alzheimer's

Alzheimer’s

More than half of drugs in current late-stage trials for Alzheimer’s disease target beta-amyloid proteins, which stick together to form plaques between nerve cells in the brain of Alzheimer’s patients. These plaques destroy surrounding cells and impair cognition.

Biogen recently announced that its antibody-based therapy, aducanumab, saw a statistically significant reduction in these plaques, as well as a slowing of mental decline at the 12-month mark. 

Another group of drugs in the Alzheimer’s pipeline to watch are the beta secretase cleaving enzyme (BACE) inhibitors, which block the production of beta-secretase, an enzyme needed for production of beta-amyloid proteins. By blocking production of the proteins rather than destroying them once they’re formed, it’s hoped these drugs may have a bigger impact.

In August 2016, AZD3293 (Lilly and AstraZeneca), an oral BACE inhibitor, received fast-track designation for the development program in Alzheimer’s disease. A pivotal Phase II/III clinical trial of AZD3293 started in late 2014 and is planned to recruit 1,500 patients and end in May 2019. In April 2016 the company announced it would advance to phase 3 without modification. According to the manufacturer, AZD3293 has been shown in studies to reduce levels of amyloid beta in the cerebro-spinal fluid of people with Alzheimer’s and healthy volunteers.

Another potential target in the treatment of Alzheimer’s are tau proteins, which form tangles inside brain cells. TauRx Pharmaceuticals’ LMTX, a second-generation tau aggregation inhibitor, acts by reducing levels of aggregated or misfolded tau proteins, which are associated with the progressive neurodegeneration which is the hallmark of Alzheimer’s disease, according to the company. At press time, TauRx had completed two large phase 3 clinical trials of LMTX in Alzheimer’s disease.

Flortaucipir (Lilly), a molecular imaging agent under investigation for detecting the presence of amyloid plaque in the brain, has been submitted to the FDA for approval.

According to the Alzheimer’s Association, plaques form when protein pieces called beta-amyloid clump together. Beta-amyloid comes from a larger protein found in the fatty membrane surrounding nerve cells.

“[Alzheimer’s disease] is unique due to the process of diagnosis, which is based on memory impairment, thinking skills, functional abilities and behavioral changes,” says Andrew Lyle, director of business development, Curexa Pharmacy. “Furthermore, the true physical tests that can be completed will only rule out other diagnoses; you can test for amyloid plaques and swelling of the brain but at that point the disease has already taken its toll.”

Erin Bastick, PharmD, RPh, is a staff pharmacist at Southwest General Health Center in Middleburg Heights, Ohio.