Specialty Drug Pipeline Monthly Update: November 2023

This monthly pipeline wrap-up provides a review of newly approved specialty drugs, recent drug launches, generic updates, new indications and news of note on drugs in the approval process.

See separate article for pipeline information on traditional drugs.

New Drugs

Loqtorzi™ (toriplalimab-tpzi): The United States (U.S.) Food and Drug Administration (FDA) approved Loqtorzi, by Coherus BioSciences, for use in combination with cisplatin and gemcitabine for the first-line treatment of adults with metastatic or recurrent locally advanced nasopharyngeal carcinoma (NPC), and as monotherapy for the treatment of adults with recurrent, unresectable, or metastatic NPC with disease progression on or after platinum-containing chemotherapy. Loqtorzi is a next generation programmed death receptor-1 (PD-1)- blocking antibody that binds to the PD-1 ligands, PD-L1 and PD-L2, and to the PD-1 receptor found on T cells. In the JUPITER-02 (NCT03581786) trial, it significantly prolonged progression-free survival by 48% when added to chemotherapy as first-line treatment.[i] In the POLARIS-02 (NCT02915432) trial, it led to an objective response rate of 20.5%, a disease control rate  of 40%, median progression-free survival of 1.9 months, and a median overall survival of 17.4 months in patients who were refractory to standard chemotherapy.[ii] The Orphan Drug is the first checkpoint inhibitor approved to treat NPC and has the potential to become part of a new standard of care for patients with NPC. Launch of Loqtorzi is expected in 1Q 2024, with pricing to follow.[iii]

Wezlana (ustekinumab-auub): The FDA approved Wezlana by Amgen, as the first biosimilar and interchangeable product to Janssen’s interleukin-12 and-23 antagonist Stelara® (ustekinumab).[iv] Biosimilars are highly similar to and have no clinically meaningful differences from their reference product and interchangeable biosimilars are expected to produce the same clinical results as the reference product in any given patient. Wezlana is approved for all indications as its reference product, which includes treatment of adults and pediatric patients ≥ 6 years of age with moderate to severe plaque psoriasis (PSO) who are candidates for phototherapy or systemic therapy, or with active psoriatic arthritis (PsA), and for adults with moderately to severely active Crohn’s disease (CD) or ulcerative colitis (UC). As with Stelara, Wezlana is approved for intravenous (IV) and subcutaneous (SC) administration; adult patients may self-administer the SC formulation. Wezlana may be available in the U.S. no later than February 21, 2025, based on a settlement agreement.[v] Pricing to follow.

Fruzaqla™ (fruquintinib): Fruzaqla, by Takeda, was FDA approved under a Priority Review for the treatment of adults with metastatic colorectal cancer (mCRC) who have been previously treated with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy, an anti-vascular endothelial growth factor (VEGF) therapy, and, if RAS wild-type and medically appropriate, an anti-epidermal growth factor receptor (EGFR) therapy. Fruzaqla is an oral kinase inhibitor that targets VEGF receptors 1, 2, and 3. Approved as oral capsules, Fruzaqla is administered once daily for the first 21 days of each 28-day cycle, and is continued until disease progression or unacceptable toxicity occurs. In the phase 3, international FRESCO-2 (NCT04322539) study, fruquintinib or placebo were added to best supportive care (BSC).[vi] After a median follow-up of 11 months, the overall survival (OS) was significantly longer in patients treated with Fruzaqla than placebo (median, 7.4 versus 4.8 months, respectively; p<0.001). The progression-free survival (PFS) was also longer with Fruzaqla compared to placebo (median, 3.7 versus 1.8 months, respectively; p<0.001). Results were consistent regardless of prior therapy. In the similarly designed, China-based, phase 3 FRESCO (NCT02314819) trial, OS and PFS were longer with Fruzagla compared to placebo (median OS, 9.3 and 6.6 months, respectively; median PFS, 3.7 and 1.8 months, respectively).[vii] Fruzaqla could compete with Lonsurf® (trifluridine/tipiracil) and/or Stivarga® (regorafenib) in the refractory mCRC space. Takeda has not announced the launch timeline for Fruzagla; pricing information to follow.

Adzynma (ADAMTS13, recombinant-krhn): The FDA approved Adzynma, a human recombinant A disintegrin and metalloproteinase with thrombospondin motifs 13 (rADAMTS13), for prophylactic or on demand enzyme replacement therapy (ERT) in adult and pediatric patients with congenital thrombotic thrombocytopenic purpura (cTTP).[viii] Adzynma replaces the deficient ADAMTS13 enzyme in patients with cTTP. It is the only pharmacologic treatment approved for the rare, inherited condition; fresh-frozen plasma (FFP) has been the standard of care. Adzynma is approved as a lyophilized powder for reconstitution for IV administration. It is given as a weight-based dose once daily as on-demand treatment of an acute event, and once weekly or every other week for prophylactic therapy. Interim analysis of an ongoing open-label, cross-over study, revealed that after a median duration of therapy of 0.7 years (range, 0-1.4 years), no patient who received Adzymna prophylaxis treatment experienced an acute TTP event or a subacute TTP event. However, among those who received FFP therapy, one patient had an acute event and 4 patients experienced subacute events (5 events total). In the on-demand cohort, 5 adults experienced an acute TTP events (6 events total), of whom 2 were assigned to Adzynma treatment and 3 received plasma-based treatment. All events in both groups resolved with on-demand treatment. Adzynma was granted Fast Track and Orphan Drug designations, as well as a Priority Review by the FDA. Takeda is expected to launch Adzynma in December 2023, with pricing to follow.[ix]

Ixchiq® (chikungunya vaccine, live): The FDA granted an Accelerated Approval for the live-attenuated vaccine, Ixchiq, for the prevention of disease caused by chikungunya virus (CHIKV) in individuals 18 years of age and older who are at increased risk of exposure to CHIKV.[x] The approval was based on anti-CHIKV neutralizing antibody titers, and continued approval may depend upon confirmatory trial results. Ixchiq is the first vaccine available to immunize against CHIKV worldwide. It is administered as a single intramuscular (IM) dose. The effectiveness of a Ixchiq in preventing disease due to CHIKV was based on a non-human primate model that reported a 98.9% seroresponse rate 28 days after a single dose. Valneva plans to launch Ixchiq in the U.S. in early 2024, after the vaccine is reviewed by the Centers for Disease Control and Prevention (CDC) Advisory Committee on Immunization Practices (ACIP) in February 2024.[xi] Pricing information will follow.

Truqap™ (capivasertib): Under a Priority Review, the FDA approved AstraZeneca’s Truqap for use in combination with fulvestrant to treat adults with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative locally advanced or metastatic breast cancer with at least one biomarker alteration (PIK3CA, AKT1 or PTEN) as detected by an FDA-approved test. Eligible patients have progressed on at least one endocrine-based regimen in the metastatic setting or experienced recurrence on or within 12 months of completing adjuvant therapy. Approved as oral tablets, Truqap is taken twice daily for 4 days, followed by 3 days off, until disease progression or unacceptable toxicity occurs. Truqap is the first AKT inhibitor approved by the FDA. In the phase 3 CAPItello-291 (NCT04305496) trial, the median progression-free survival was over twice as long when Truqap was added to fulvestrant compared to fulvestrant alone among patients with AKT pathway–altered tumors (7.2 versus 3.6 months, respectively; p<0.001).[xii] The objective response rates in the overall population arms were 26% and 8%, respectively, with complete response rates of 2.3% and 0%, respectively. AstraZeneca has not announced the timeframe for launch of Truqap. Pricing will follow.

Augtyro™ (repotrectinib): Under a Priority Review, the FDA approved Augtyro, a tyrosine kinase inhibitor (TKI), for the treatment of adults with locally advanced or metastatic ROS1-positive non-small cell lung cancer (NSCLC). ROS1 fusions are estimated to occur in about 1% to 2% of patients with NSCLC. In the single-arm, open-label, phase 1/2 TRIDENT-1 (NCT 03093116) trial, Augtyro led to overall response rates of 79% in ROS1 TKI-naïve patients and 38% in patients who received prior ROS1-targeted TKI therapy. The median duration of response was 34.1 and 14.8 months, respectively, in each group. The Orphan Drug is approved as oral capsules to be taken once daily for the first 14 days, and twice daily thereafter, until disease progression or unacceptable toxicity occurs. Bristol-Myers Squibb plans to launch the Augtyro in mid-December 2023, with pricing to follow.[xiii]

New Indications

Vabysmo® (faricimab-svoa): Vabsymo, by Genentech, received a new indication from the FDA for the treatment of macular edema following retinal vein occlusion (RVO).[xiv] It is administered via intravitreal injection every 4 weeks.

Cosentyx® (secukinumab): Novartis’ interleukin-17A antagonist Cosentyx received a new indication for the treatment of adults with moderate to severe hidradenitis suppurativa (HS).[xv] The recommended dosage for HS is 300 mg SC once weekly for the first 5 doses, and every 4 weeks thereafter. If the patient does not respond to every 4 week dosing, 300 mg every 2 weeks may be considered. Cosentyx could compete with adalimumab products (Humira and its biosimilars) in the HS space.

Idacio® (adalimumab-aacf): The FDA approved a new indication for Fresenius Kabi’s Idacio, a biosimilar to Abbvie’s Humira® for the treatment of noninfectious intermediate, posterior and panuveitis in adult patients.[xvi] Idacio is now approved for most indications that its reference product carries, with the exception of UC and uveitis in pediatric patients.

Keytruda® (pembrolizumab): The FDA approved Merck’s PD-1 blocking antibody Keytruda for use in combination with gemcitabine and cisplatin, for the treatment of patients with locally advanced unresectable or metastatic biliary tract cancer (BTC).[xvii] Use of Keytruda for BTC was previously limited to second-line therapy in select patients (microsatellite instability-high [MSI-H] and/or deficient mismatch repair [dMMR], or tumor mutational burden-high [TMB-H]).

Orencia® (abatacept): The FDA approved an expanded indication for Bristol-Myers Squibb’s Orencia for the treatment of active psoriatic arthritis (PsA) to include pediatric patients ≥ 2 years of age.[xviii] For the new population, Orencia is administered SC as weight-based doses and may be used in combination with methotrexate. IV administration of Orencia is not approved for pediatric patients with PsA.

New Formulations

Adalimumab – The FDA approved a supplemental biologics license application (sBLA) by Abbvie for unbranded product labeling for adalimumab.^[xix] Adalimuamb is also approved as branded Humira® by Abbvie.

Adalimumab-aacf: The FDA approved an sBLA for unbranded biological product labeling for Fresenius Kabi’ adalimumab-aacf.^[xx] Adalimumab-aacf is also approved as branded Idacio®, a biosimilar of Humira.

References

[i] JUPITER-02 trial. https://www.nature.com/articles/s41591-021-01444-0.

[ii] POLARIS-02 trial. https://ascopubs.org/doi/full/10.1200/JCO.20.02712.

[iii] Press Release. https://investors.coherus.com/news-releases/news-release-details/coherus-and-junshi-biosciences-announce-fda-approval-loqtorzitm.

[iv] Wezlana labeling. https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/761285s000,761331s000lbl.pdf.

[v] Press release. https://www.tevapharm.com/news-and-media/latest-news/alvotech-and-teva-secure-u.s.-license-date-for-avt04-a-proposed-biosimilar-to-stelara.

[vi] FRESCO-2 trial. https://www.thelancet.com/article/S0140-6736(23)00772-9/fulltext.

[vii] FRESCO trial. https://jamanetwork.com/journals/jama/fullarticle/2685988.

[viii] Adzynma labeling. https://www.fda.gov/media/173756/download.

[ix] News. https://www.reuters.com/business/healthcare-pharmaceuticals/us-fda-approves-takedas-blood-disorder-therapy-2023-11-09.

[x] Ixchiq labeling: https://www.fda.gov/media/173758/download?attachment.

[xi] News. https://www.drugs.com/newdrugs/fda-approves-ixchiq-chikungunya-vaccine-live-prevention-caused-chikungunya-virus-6140.html.

[xii] CAPItello-291 trial. https://www.nejm.org/doi/pdf/10.1056/NEJMoa2214131?articleTools=true.

[xiii] Press release. https://news.bms.com/news/corporate-financial/2023/US-Food-and-Drug-Administration-Approves-Augtyro/default.aspx.

[xiv] Vabysmo labeling. https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/761235s003lbl.pdf

[xv] Cosentyx labeling. https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/125504s063lbl.pdf.

[xvi] Idacio labeling. https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/761255s003lbl.pdf.

[xvii] Keytruda labeling: https://www.merck.com/product/usa/pi_circulars/k/keytruda/keytruda_pi.pdf.

[xviii] Orencia labeling: https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/125118s250lbl.pdf.

[xix] Adalimumab labeling: https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/125057s423lbl.pdf.

[xx] Adalimumab-aacf labeling: https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/761255s004lbl.pdf.