Specialty Drug Pipeline Updates for 2022

Specialty drugs are having a moment: Between 2015 and 2021, specialty pharmacies grew by 315%, according to data presented at Asembia’s 2022 Specialty Pharmacy Summit,¹ with hospital or health system–owned specialty pharmacies accounting for one-third of the total growth.

The specialty drug pipeline has expanded accordingly, with an expected continued growth of 8% per year through 2025.² At the 2022 American Society of Health-System Pharmacists (ASHP) Summer Meetings & Exhibition, held in June in Phoenix, Arizona, 2 sessions^3,4 broke down the latest updates and highlighted some of the most notable drugs in the pipeline. Keep reading for a selection of pipeline updates in oncology and immunology and visit drugtopics.com for full coverage of each of these sessions.

Next-in-Class Treatments Lead Oncology Drug Pipeline

According to Sandra Cuellar, PharmD, we’re living in the golden age of oncology.¹

Sandra Cuellar, PharmD

“If you look at the past decade of FDA oncology approvals, we have made remarkable progress with immune checkpoint inhibitors, with sophisticated biologic agents such as antibody-drug conjugates, bispecific monoclonal antibodies, [and] targeted therapies,” Cuellar, a clinical associate professor and clinical oncology pharmacist at UI Health/ University of Illinois at Chicago College of Pharmacy, said during her presentation.³ “In the past decade or so...the number of drug approvals in oncology is over 330.”

The majority of these approvals (59%) are for label expansion. The poster child, she added, is pembrolizumab (Keytruda), which has 33 indications over 13 individual disease states. Twenty-five percent of approvals were the first approval of a next-in-class drug, and 16% were for drugs with a new mechanism of action, with 7 such drugs approved in 2020.

Melanoma

According to Cuellar, melanoma was one of the first cancers that saw the efficacy of immune checkpoint inhibitors (ICIs).“In this particular cancer, we had very poor outcomes,” she said. “The approval of [ICIs] really did improve outcomes.” To build on that success, researchers turned to LAG3, an immune checkpoint protein that is upregulated in melanoma.

Nivolumab Plus Relatlimab-rmbw Combination Therapy

Preclinical data support the idea of using nivolumab and relatlimab-rmbw (Opdualag), 2 dual ICIs that have demonstrated synergistic activity. Results of the RELATIVITY-047 trial (NCT03470922), which evaluated the efficacy of nivolumab and relatlimab-rmbw combination therapy in a global, randomized, double-blind phase 3 trial, demonstrated that in a population of 694 patients with untreated unresectable or metastatic melanoma, the median progression free survival rate was 10.12 months vs 4.63 months with nivolumab therapy alone.

Nivolumab and relatlimab-rmbw (Opdualag) is a first-in-class therapy approved by the FDA on March 18, 2022, for the frontline treatment of adult and pediatric patients 12 years or older with unresectable or metastatic melanoma. It is formulated as an injection of 240 mg nivolumab and 80 mg relatlimab per 20 mL (12 mg and 4 mg per mL) and administered in adults and pediatric patients weighing at least 40 kg as 480 mg nivolumab and 160 mg relatlimab intravenously over a 30-minute period every 4 weeks.

Non–Small Cell Lung Cancer (NSCLC)

“As an oncology pharmacist...this has been probably the most remarkable progress I have witnessed,” said Cuellar. “Why is that? We started out 20-plus years ago treating [NSCLC] as 1 disease,” typically with paclitaxel and carboplatin (CarboTaxol). However, Cuellar explained, patients were frequently experiencing negative outcomes, leading to a shift in thinking around the disease and an understanding that different histologies of NSCLC require different therapies, including squamous cell and adenocarcinoma. Today, patients with NSCLC undergo tissue or liquid biopsy and next-generation tumor sequencing to determine which oncogenic mutation is driving their disease.

Poziotinib

Over time, researchers have continued to identify mutations responsible for driving NSCLC, including in HER2. Between 2% and 3% of patients with NSCLC have a HER2 mutation, most commonly an exon 20 insertion, representing an unmet need in therapy.

Enter poziotinib, a potent, irreversible inhibitor of cancers with EGFR and HER2 exon 20 mutations. The phase 2 ZENITH20 clinical trial (NCT03318939) included 7 cohorts of patients with either EGFR or HER2 exon 20 mutations. Cuellar focused on patients in cohort 2, which included those with HER2 exon 20 insertion mutations who were previously treated and received an oral, once-daily dose of poziotinib 16 mg. In total, 27.8% of patients met the primary end point of overall response rate; duration of response was 5.1 months, and median progression-free survival was 5.5 months.

Poziotinib is a next-in-class investigational therapy with a likely indication for metastatic NSCLC with HER2 exon 20 insertion mutations with an anticipated Prescription Drug User Fee Act (PDUFA) date of November 24, 2022. Tentative dosing is oral, 16 mg once daily until progression or unacceptable toxicity.

Patritumab Deruxtecan

“Up to 30% of [patients with NSCLC] have an EGFR-activating mutation,” said Cuellar. “Of these EGFR mutations, about 83% express HER3 protein,” which is associated with increased metastases, decreased survival, and increased resistance. Cuellar noted that although there are several approved treatments for patients with EGFR mutations, there are limited treatments available for those who progress or have resistance to first-line EGFR tyrosine kinase inhibitor agents.

Patritumab deruxtecan, an investigational, first-in-class HER3-directed antibody-drug conjugate, may one day be an option for this group of patients. In a multicenter, open-label, multicohort phase 1 trial (NCT03260491), researchers identified a dose of 5.6 mg/kg administered intravenously every 3 weeks as the correct dose for a dose expansion trial. Efficacy of this dose was evaluated in 57 patients, while safety and tolerability of all doses, ranging from 3.2 mg/kg to 6.4 mg/kg, were evaluated in 81 patients.

Within the cohort, median time to response was 2.6 months, median duration of response was 6.9 months, and median progression-free survival was 8.2 months. “[These are] very early preliminary data, but [this is] very promising, especially in a patient population that’s heavily pretreated,” said Cuellar. Adverse events were common; 11% led to treatment discontinuation, 21% led to dose reduction, and 37% led to dose interruption.

Patritumab deruxtecan was granted an FDA breakthrough therapy designation on December 23, 2021. Tentative dosing is 5.6 mg/kg intravenously every 3 weeks until progression or unacceptable toxicity.

Adagrasib

The KRAS G12C mutation occurs in approximately 13% of cases of NSCLC. Adagrasib is an investigational drug that irreversibly and selectively binds to KRAS G12C in its inactive state, blocking both cell growth and proliferation.

The nonrandomized, open-label, phase 1/2 KRYSTAL-1 study (NCT03785249) evaluated adagrasib in patients with KRAS G12C–mutated solid tumors or unresectable or metastatic disease who had progressed on standard treatment. “The phase 1 study demonstrated that the dose that was going to be further investigated was 600 mg twice a day,” Cuellar explained. “In the phase 2 component, they looked at monotherapy in [NSCLC], colon cancer, and other solid tumors.”

In an NSCLC cohort of 79 patients, adagrasib demonstrated an overall response rate of 58% with a 9.5- month median duration of treatment, 12.6-month median duration of response, and 8.3-month progression-free survival; 36% of participants experienced grade 3/4 adverse events.

As a next-in-class drug, adagrasib received an FDA Breakthrough Therapy designation on June 25, 2021, and has an anticipated PDUFA date of December 14, 2022. The drug is administered orally with a tentative dosing of 600 mg twice daily until progression or unacceptable toxicity.

Breast Cancer

According to Cuellar, the most common type of breast cancer—both in her practice and in the United States—is hormone receptor–positive breast cancer. “Endocrine therapy is the backbone in the treatment of hormone-positive breast cancer,” she said. “And unfortunately, although we do have good efficacy outcomes with endocrine therapy, we do see up to 42% of patients do [become resistant] to endocrine therapies.”

Mutations the ESR1 gene that inhibit its localization to the plasma membrane are one of the “primary culprits” of endocrine therapy resistance. “We do have selective estrogen receptor degraders, or SERDs, that are indicated in the metastatic setting and have demonstrated some efficacy in patients with mESR1 metastatic breast cancer,” Cuellar explained, including fulvestrant (Faslodex), administered to patients via intra- muscular injection.

Elacestrant

Data from the EMERALD trial (NCT03778931), initially presented at the 2021 San Antonio Breast Cancer Symposium, highlighted elacestrant, an investigational, nonsteroidal, orally bioavailable SERD. The global, open-label, randomized, phase 3 trial included patients (men and postmenopausal women) with estrogen receptor–positive, HER2-negative advanced or metastatic breast cancer who had progressed after 1 or 2 lines of endocrine therapy treatment, one of which included a CDK4/6 inhibitor. Patients received elacestrant or standard of care, either fulvestrant or an aromatase inhibitor.

“This is a very resistant patient population,” Cuellar said. “Unless [patients] have visceral crisis or symptomatic visceral disease, the standard of care in treating these patients is exhausting these endocrine options.”

Other oral SERDs in development include giredestrant and amcenestrant, both in phase 2 and phase 3 trials; rintodestrant, currently in phase 1 research; and camizestrant, currently being evaluated in 2 phase 3 trials and 1 phase 2 trial. Elacestrant is a next-in-class investigational therapy that has received an FDA fast track designation. Tentative dosing is 400 mg orally daily until progression or unacceptable toxicity.

Immunology Pipeline Includes New Approvals and Expanded Indications

Immunology drugs represent a significant portion of the pipeline and are forecast as a key area of growth for specialty pharmacy. Caitlyn Anne Young, PharmD, a PGY-2 investigational drugs and research pharmacy resident at Michigan Medicine in Ann Arbor, shared⁴ the latest updates in immunology therapies with a specific focus on dermatology, gastroinestinal, and respiratory conditions.

Dermatology

Dermatology updates were focused on atopic dermatitis, plaque psoriasis, and psoriatic arthritis.

Caitlyn Anne Young, PharmD

Abrocitinib

Abrocitinib (Cibinqo) was FDA approved in January 2022 for the treatment of moderate to severe atopic dermatitis (AD), with a recommendation for use in cases refractory to treatment after biologic therapies and other disease-modifying anti-rheumatic drugs have been trialed— making abrocitinib a second-line therapy for the disease.

Data from the JADE clinical trials (NCT03349060, NCT03575871, and NCT03720470), which compared abrocitinib vs placebo and dupilumab (Dupixent), contributed to the approval. Most notably, Young said, abrocitinib demonstrated rapid control over itch response, a secondary end point that is particularly important for patients’ quality of life. Some dose-dependent adverse events were observed, including thrombocytopenia with increased dose levels, she added.

Prior authorization requirements vary, but typically, patients must have tried and failed at least 1 high-potency, topical corticosteroid and at least 1 systemic therapy before abrocitinib approval will be granted. Abrocitinib is available as a once-daily 100-mg oral tablet with a maximum daily dose of 200 mg.

Deucravacitinib

Deucravacitinib is a novel, first-in- class selective oral tyrosine kinase 2 inhibitor for moderate to severe plaque psoriasis with an anticipated FDA approval date of September 2022. The drug inhibits signaling of IL-23, IL-12, and type 1 interferons without inhibiting Janus kinase (JAK) 1, 2, or 3.

In the POETYK-PSO1 and POETYK-PSO2 clinical trials (NCT03624127 and NCT03611751, respectively), investigators compared deucravacitinib with placebo and apremilast (Otezla) 30 mg twice daily, which is the current standard-of-care dosing for moderate to severe plaque psoriasis. “In terms of its primary and secondary end points, [deucravacitinib] performed really, really well,” said Young. “There are really promising outcomes here with no really alarming safety signals.” Deucravacitinib is formulated as an oral, once-daily 6-mg tablet.

Bimekizumab

Bimekizumab (Bimzelx) is another drug aimed at treating moderate to severe plaque psoriasis with “a little bit of a different mechanism of action compared with the other IL-17 monoclonal antibodies,” said Young. “IL-17 is thought to be proinflammatory and heavily involved in inflammation... compared with [tumor necrosis factor α (TNF-α)]. However, IL-17F is also expressed specifically in psoriatic skin lesions.”

Three clinical trials—BE VIVID (NCT03370133), BE SURE (NCT03412747), and BE RADIANT (NCT03536884)—compared bimekizumab with ustekinumab, adalimumab, and secukinumab, respectively; in all trials, bimekizumab demonstrated superiority in primary clinical end points. However, Young added, “one thing to note is that [bimekizumab shows] much higher rates of oral candidiasis...so patients will need to be counseled on the potential development of thrush.”

In May 2022, the FDA issued a complete response letter indicating that the approval process will be halted until certain preapproval indication criteria are addressed. “Although it was anticipated for possible approval later this year, we may be looking more so to 2023,” Young added. Bimekizumab is formulated as a subcutaneous injection and dosed at 320 mg every 4 weeks with maintenance dosing every 4 to 8 weeks.

Gastrointestinal Label Expansions

“We’re seeing a lot of label expansions happening for currently marketed drugs,” said Young. Two drugs on that list are being investigated for potential label expansions to treat both ulcerative colitis (UC) and Crohn disease: risankizumab (Skyrizi), an IL-23 IgG1 monoclonal antibody indicated for moderate to severe plaque psoriasis and psoriatic arthritis (PsA), with a projected 2022 third quarter approval; and guselkumab (Tremfya), another IL-23 IgG1 monoclonal antibody approved for plaque psoriasis and PsA projected to be approved in 2023. Upadacitinib (Rinvoq)—a JAK-STAT inhibitor currently also approved for AD, rheumatoid arthritis (RA), and PsA—received FDA approval of the label expansion in March 2022.

Other drugs seeking label expansion for gastrointestinal conditions include golimumab (Simponi), an anti–TNF-α monoclonal antibody for RA, PsA, ankylosing spondylitis, and UC in adults. Approval is being sought for the treatment of UC in children and adolescents aged 2 to 17 years and is projected for 2023. Vedolizumab (Entyvio) is an α4β7 integrin inhibitor already approved for UC and Crohn disease; the proposed indication is a subcutaneous formulation for UC therapy slated for 2023.

Ozanimod (Zeposia), a S1P receptor modulator for UC and multiple sclerosis, is currently under investigation as a therapy for Crohn disease. This drug rounded out the list, with a projected approval date of 2024.

The Respiratory Pipeline

“[Respiratory therapies] have been a little bit slower in terms of pipeline development, with only 1 really notable medication that [was] approved late last year,” said Young.

That drug was tezepelumab (Tezspire), an add-on maintenance treatment for asthma in patients 12 years and older, which Young described as “a broad indication compared with other biologic medications in this class.” Rather than using other therapies off label, first-in-class tezepelumab offers patients an on-label monoclonal antibody option with a novel mechanism of action: It is a thymic stromal lymphopoietin (TSLP) blocker, IgG2λ monoclonal antibody that binds to human TSLP and blocks interaction with the TSLP receptor.

The pivotal NAVIGATOR and PATHWAY trials (NCT03347279 and NCT02054130) demonstrated strong efficacy and safety, with minimal adverse events noted.

Tezepelumab was approved by the FDA in December 2021 and is dosed as a 210-mg subcutaneous injection every 4 weeks; compared with other monoclonal antibodies on the market, it must be administered in a clinic by a health care provider.

By the numbers

References

1. Fein A, Long D. The Specialty Pharmacy Industry Update and Outlook. Presented at: Asembia Specialty Pharmacy Summit; May 2-5, 2022; Las Vegas, NV.
2. Carter H. Three specialty drug trends to prepare for: biosimilars, gene and cell therapies, cancer drugs. Evernorth. April 20, 2022. Accessed June 20, 2022. https://www.evernorth.com/articles/specialty-drug-pipeline-biosimilars-and-more 
3. Cuellar S, Banks AM. Specialty pipeline updates I: hematology & oncology. Presented at: American Society of Health-System Pharmacists Summer Meetings & Exhibition; June 11-15, 2022; Phoenix, AZ
4. Young CA, Pleva M, Banks AM. Specialty pipeline updates II: autoimmune and emerging therapies. Presented at: American Society of Health-System Pharmacists Summer Meeting & Exhibition; June 11-15, 2022; Phoenix, AZ.