Impactful Pipeline Drugs Primed for Approval in 2024
By Emily Crisano, PharmD and Jason Peterson, R.Ph
This year has kicked off with notable advancements in drug approvals from the Food and Drug Administration (FDA). Noteworthy among them is the approval of Rezdiffra (resmetirom) in mid-March, the first drug ever for Non-Alcoholic Steatohepatitis (NASH). Following closely was the approval of Winrevair (sotaercept-csrk), a pioneering activin signaling inhibitor for treating Pulmonary Arterial Hypertension (PAH). As 2024 progresses, we anticipate the approval of several impactful drugs that are currently in the pipeline and could make a significant mark by year-end. Here, we highlight five promising agents that are poised to make a significant impact on both payers and consumers.
1. Ipsen’s Elafibranor
Elafibranor is an investigational dual peroxisome activated receptor (PPAR) -alpha and -delta agonist that has been developed by Ipsen and is under evaluation for the treatment of Primary Biliary Cholangitis (PBC), a rare liver disease.
What is PBC?
PBC is characterized as an ongoing immunologic attack on the intralobular bile ducts. This continuous assault on the bile duct epithelial cells leads to their gradual destruction and eventual disappearance. The sustained loss of intralobular bile ducts causes the signs and symptoms of cholestasis and eventually results in cirrhosis and liver failure. Among patients with symptoms, fatigue and pruritus are the most common at presentation.
Historical Treatments
Ursodiol, ursodeoxycholic acid, has been the mainstay of therapy for PBC patients. Dosing is based on the patient’s body weight and administered orally twice daily. Ursodiol is a relatively inexpensive agent with a cost around $150 per month, based on the average adult weight of 176 pounds. Therapy for PBC is life-long to preserve the function of the intralobular ducts of the liver. Improvement in liver biochemical tests (i.e., alkaline phosphatase [ALK]) is typically observed within three months of starting ursodiol, although symptoms such as fatigue often do not improve with treatment.
If a patient does not respond appropriately to ursodiol through evidence of their ALK being above the upper limit of normal after one year on therapy, then Ocaliva (obeticholic acid) can be added onto ursodiol or used alone. Treatment with Ocaliva per month is $9,554. However, if the patient is already showing signs of cirrhosis or has established cirrhosis, then Ocaliva use is contraindicated because it can lead to hepatic decompensation or liver failure.
Pipeline Drug: Elafibranor
In 2019, elafibranor was granted a Breakthrough Therapy Designation by the FDA in adults with PBC who have an inadequate response to ursodiol. Elafibranor is an orally administered once-daily treatment designed to target the impairment of bile flow in the liver, bile toxicity, inflammation/fibrosis, and bile acid output. In a clinical trial, elafibranor performed better than placebo in patients who had previously tried ursodiol, resulting in higher rates of normalized liver function as measured by ALK.
While the exact cost of elafibranor has yet to be released, we can expect it to be near $10,000 range, similar to Oclavia. Elafibranor may be cost prohibitive in some instances, when compared to the monthly cost of ursodiol. However, particularly for patients with cirrhosis where Ocaliva would be contraindicated, elafibranor would present a new line of treatment for these patients that would have previously only had ursodiol as an option.
We expect elafibranor to be approved in June 2024 and to be used as a second-line treatment to those that don’t respond to or are intolerant to treatment with ursodiol.
2. Novo Nordisk’s Awiqli (Insulin Icodec)
Recently, manufacturer Novo Nordisk revealed the trade name, Awiqli, for insulin icodec. The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has issued a positive opinion, recommending its authorization to the European Medicines Agency, Europe’s counterpart to the FDA. While no specific FDA-approval date has been announced, global approval seems imminent.
What is it?
Insulin icodec, an ultra-long-acting basal insulin, is designed to maintain steady glucose levels both day and night for individuals with Type 1 and Type 2 diabetes mellitus. While several long-acting basal insulins are currently available, they all require daily dosing. If approved by the FDA, Awiqli would be the first once-weekly basal insulin option for adults with diabetes, offering a significant advancement in convenience. This dosing schedule aligns with that of GLP-1 agonists, a well-known therapeutic class in Type 2 diabetes management, which also features once-weekly administration. The once-weekly dosing not only simplifies the regimen but has also been shown to enhance patient adherence and improve overall treatment outcomes.
Effectiveness & Safety
Novo Nordisk has completed six phase 3 ONWARD clinical trials, comparing Awiqli head-to-head with once-daily basal insulins in over 4,000 patients, including those new to insulin and those switching from other basal insulins. In all ONWARD trials, Awiqli demonstrated equivalent or superior efficacy in reducing hemoglobin A1c (HbA1c) levels—a crucial marker in diabetes management that indicates average blood sugar levels over the past two to three months. However, it's important to note that some trials reported a higher incidence of hypoglycemia (low blood sugar). Prescribers should consider this when evaluating candidates for this therapy, weighing the benefits of less frequent dosing against the potential risks.
Cost & Payer Considerations
Just as in other consumer markets, convenience in healthcare often carries a premium price tag. For daily-administered basal insulins, using an average dosage of 50 units per day—which translates to one carton of five pens—the Wholesale Acquisition Cost (WAC) varies significantly, ranging from $92 to over $500 per month. Typically, higher WAC products offer greater rebate opportunities, while those with lower WACs may offer minimal to no rebates.
For Awiqli, the estimated WAC is expected to fall between $700 and $1200 per month, potentially accompanied by substantial rebates in the range of 50 to 70%. After applying manufacturer discounts and rebates, the net cost to payers could be between $200 and $400 per month. Furthermore, Novo Nordisk may consider bundling Awiqli with its other diabetes management products to optimize formulary coverage with payers or PBMs.
The once-weekly convenience of Awiqli may prompt significant shifts from daily basal insulins, particularly among the Type 2 diabetes population. However, if the pricing of Awiqli significantly exceeds that of other basal insulins, it may lead to the implementation of step therapy with daily insulins and possibly a requirement for prior authorization (PA). This PA would necessitate a clinical justification for why a patient cannot use daily basal insulins. The potential FDA approval of Awiqli could mark a significant advancement in diabetes treatment options, particularly if Novo Nordisk maintains a competitive pricing strategy.
3. Verona Pharma’s Ensifentrine
Ensifentrine, developed by Verona Pharma, is an investigational novel phosphodiesterase (PDE) 3 & 4 inhibitor under review for the treatment of chronic obstructive pulmonary disease (COPD). If approved, this would be the first new mechanism of action to enter the COPD space in over a decade.
What is COPD?
COPD is a common respiratory condition associated with symptoms of cough, shortness of breath, and airflow limitation. COPD is one of the top causes of death each year in the U.S., responsible for nearly 120,000 deaths annually. Tobacco smoke, air pollutants within the home or work environments, genetics, and respiratory infections all play a role in the development of COPD.
Current Treatments
Currently, common maintenance therapies for COPD include inhaled long-acting beta-agonists (LABAs), long-acting muscarinic antagonists (LAMAs) and inhaled anti-inflammatory agents (ICSs). The standard of care for most patients with COPD is dual bronchodilator therapy using a LAMA and LABA agent. Triple therapy, or LAMA/LABA/ICS, is reserved as an alternative to dual therapy in patients with elevated blood eosinophils and a consistent history of exacerbations.
Options for patients that continue to experience exacerbations despite optimal therapy with a LAMA/LABA/ICS remain limited. Potential add-ons to therapy include Daliresp (roflumilast), a PDE-4 inhibitor, or chronic azithromycin, an antibiotic. These options have not been studied in head-to-head trials and therefore, the choice of agent is based largely on the side effect profile. Roflumilast is associated with gastrointestinal side effects and chronic azithromycin may lead to hearing loss and may affect the QTc interval (a measurement of the heart’s electrical properties).
Roflumilast falls under a similar pharmacological category as ensifentrine. Roflumilast is an oral PDE-4 inhibitor that is used to reduce the risk exacerbations in patients with severe COPD and a history of frequent COPD exacerbations (e.g., at least two per year or one requiring hospitalization). Roflumilast works by decreasing airway inflammation and promoting airway smooth muscle relaxation. The added benefit of roflumilast therapy as an add-on to the standard of care agents (LAMA, LABA, ICS) appears modest and therefore, roflumilast has had limited use in clinical practice.
Pipeline Drug: Ensifentrine
Ensifentrine works on two phosphodiesterase receptors in the lungs, which results in multiple benefits: relaxation of muscle contraction and a decrease in airway inflammation, mucus production and clearance. The dual inhibition of PDE-3 and PDE-4 has demonstrated both bronchodilation and anti-inflammatory properties in studies. This is unique compared to currently available agents for COPD that work on either bronchodilation or inflammation, but not both simultaneously.
Costs & Payer Considerations
We can expect ensifentrine to be used as an add-on to maintenance therapy for patients that remain uncontrolled despite optimal dual or triple therapy. Most of the therapies for COPD utilize a handheld inhaler device, however ensifentrine is administered via nebulizer, which is not as convenient. Approval is expected to arrive in June of 2024 for ensifentrine. Until the GOLD guidelines are updated to include this new agent, we will have to rely on prescribing patterns of clinicians to understand ensifentrine’s purpose and benefit in COPD.
The estimated annual cost of currently available nebulized products for COPD (Yupelri, Brovana, and Perforomist) range from $13,000 to $15,000. There is potential for ensifentrine to be priced higher based on its dual mechanism of action on the phosphodiesterase receptors in the lungs and therefore it is estimated to fall between a range of $15,000 to $25,000 annually.
4. Lykos Therapeutics’ Midomafetamine (MDMA)
MDMA, also known as ecstasy, is under review in combination with psychological intervention, including psychotherapy and other supportive services, for patients with moderate-to-severe post-traumatic stress disorder (PTSD). MDMA, a DEA Schedule I Controlled Substance, is a type of psychoactive compound that can increase self-awareness. MDMA, produced by Lykos Therapeutics, was granted Breakthrough Therapy Designation by the FDA in 2017 for the treatment of PTSD.
What is PTSD?
PTSD is characterized by intrusive thoughts, nightmares and flashbacks of past traumatic events, avoidance of reminders of trauma, hypervigilance, and sleep disturbance, all of which lead to considerable social, occupational, and interpersonal dysfunction.
Current Treatments
Evidence from trials have found trauma-focused therapies including trauma-focused cognitive-behavioral therapy, exposure-based therapy (e.g., prolonged and written exposure), and eye movement desensitization and reprocessing therapy to be effective in the treatment of PTSD in adults. For most adults diagnosed with PTSD, first-line treatment with trauma-focused psychotherapy that includes exposure is recommended.
In patients with co-diagnoses, such as depression and psychosis, it is recommended to begin treatment with a selective serotonin reuptake inhibitor (SSRI) until the individual’s symptoms are stable and then add psychotherapy. Medication treatment is continued for at least six months to one year to prevent relapse or recurrence. If a patient fails at least two serotonin inhibitors, the next step is treatment with a second-generation antipsychotic (SGA) medication, such as quetiapine or risperidone.
Pipeline Drug: Midomafetamine
MDMA has been studied as a treatment for PTSD and seems effective when combined with a specific, intensive form of psychotherapy. MDMA affects various neurotransmitters in the brain, including serotonin, norepinephrine, and dopamine. It's believed that MDMA may decrease a patient's fear response, which then helps to facilitate therapy sessions dealing with trauma. In a trial of 100 patients with moderate or severe PTSD, a greater percentage of those in the MDMA group no longer met criteria for PTSD as compared with the placebo group.
Costs & Payer Considerations
Estimates put MDMA at around $5,000 to $10,000 WAC for a 12-week course, but this estimated price does not reflect the anticipated clinician-associated costs of MDMA-assisted therapy, and no formal pricing has been released. While research combining MDMA & assisted therapy is promising, further trials are warranted. This agent will require a high-level of monitoring and dosing given only during physician visits to help mitigate the abuse/misuse potential. This therapy will be used in patients with moderate to severe PTSD who have not responded to other therapies used to treat the condition alongside exposure-based psychotherapy to ensure optimal safety and effectiveness.
5. Bristol Myers Squibb’s KarXT (xanomeline-trospium)
KarXT, a novel treatment for schizophrenia in adults, combines two drugs: xanomeline, which targets the M1 and M4 muscarinic receptors in the brain, and trospium, which mitigates xanomeline's side effects by blocking peripheral muscarinic receptors. This unique mechanism focuses xanomeline's effects on the central nervous system, distinguishing KarXT from most current treatments that target dopamine receptors and often cause sedation, weight gain, and other significant side effects. Trospium is already FDA-approved for over-active bladder.
What is it?
KarXT, developed by Karuna Therapeutics and now under Bristol Myers Squibb after their recent acquisition, could become the first new pharmacological approach to treating schizophrenia in decades. In three phase 3 placebo-controlled EMERGENT trials, KarXT significantly improved schizophrenia symptoms without the typical adverse effects associated with current therapies. KarXT’s most common side effects, including constipation and dizziness, were mild to moderate.
Costs & Payer Considerations
KarXT is also being explored for Alzheimer’s disease psychosis. Priced competitively with recent therapies like Lybalvi and Caplyta, ranging from $1,500 to $2,500 per month, KarXT promises fewer side effects, potentially justifying its premium cost. Schizophrenia affects nearly 24 million people globally, with about 2.8 million in the U.S. alone. Many do not fully respond to existing treatments, underscoring the urgent need for innovative options like KarXT.
Pending FDA approval expected by September 26, 2024, KarXT’s challenge will be ensuring accessibility, as it might initially face exclusion from formularies. However, with strategic rebates and marketing, Bristol Myers Squibb aims to enhance KarXT’s market presence.
As 2024 continues to unfold, the pharmaceutical landscape is poised for transformative changes with several promising drugs nearing FDA approval. From innovative treatments like Elafibranor for Primary Biliary Cholangitis to potential breakthroughs like Awiqli for diabetes, these developments promise to enhance treatment efficacy and patient convenience across a spectrum of diseases. These advancements are not just about bringing new drugs to market. They represent a leap forward in our understanding and management of complex conditions, emphasizing patient-centered care and improved quality of life.
For payers, the introduction of these drugs brings considerations of cost-effectiveness and reimbursement strategies. While newer treatments often come with higher price tags, their potential to reduce long-term healthcare costs through improved outcomes could justify initial investments. Payers will need to balance these factors carefully to optimize healthcare spending without compromising on the quality of care provided. As we continue to monitor these developments, the interaction between clinical benefits and economic impact will be crucial in shaping healthcare policies and practices moving forward.