Specialty Pipeline Quarterly Update: December 2022

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

See separate articles for pipeline information on traditional drugs, biosimilars and cell/gene therapy. 

New Drug Information

• Tzield^® (teplizumab-mzwv): The U.S. Food and Drug Administration (FDA) approved Provention Bio’s Tzield injection to delay the onset of stage 3 type 1 diabetes in adults and pediatric patients 8 years and older who currently have stage 2 type 1 diabetes. Tzield is administered by intravenous (IV) infusion once daily for 14 consecutive days. The efficacy of Tzield was evaluated in a Phase 2, randomized, double-blind, event-driven, placebo-controlled trial in 76 patients with stage 2 type 1 diabetes. The primary measure of efficacy was the time from randomization to development of stage 3 type 1 diabetes diagnosis. The trial results showed that over a median follow-up of 51 months, 45% of the 44 patients who received Tzield were later diagnosed with stage 3 type 1 diabetes, compared to 72% of the 32 patients who received a placebo. The mid-range time from randomization to stage 3 type 1 diabetes diagnosis was 50 months for the patients who received Tzield and 25 months for those who received a placebo.¹In 2021 the Endocrinologic and Metabolic Drugs Advisory Committee voted 10-7 that the benefits of teplizumab outweighed its risks, with many panelists “struggling” to come down on one side or the other. Panel members raised concerns about how small the study was—it didn’t meet its enrollment goal and wound up testing teplizumab in just 44 patients—and about the fact that the study did not follow patients after their diabetes diagnosis. Multiple panelists pointed to a higher rate of serious side effects in the 44 patients who received teplizumab, compared to the 32 who got placebo (16% versus 3%), as well as three patient deaths in the teplizumab arm compared to none in the placebo group.² Tzield has launched with an average wholesale price (AWP) $16,620 per vial. The infused treatment will carry a list price of $13,850 per vial, which works out to $193,900 for a 14-vial (one per day for 14 days) regimen for the average-sized patient.
• Rebyota^® (fecal microbiota, live-jslm): The FDA approved Ferring’s (Rebiotix) Rebyota for the prevention of recurrence of Clostridioides difficileinfection (CDI) in individuals 18 years of age and older. It is for use after an individual has completed antibiotic treatment for recurrent CDI. In the United States, the infection is associated with 15,000-30,000 deaths annually. Rebyota is administered rectally as a single dose. Rebyota is prepared from stool donated by qualified individuals. The donors and the donated stool are tested for a panel of transmissible pathogens, however, as Rebyota is manufactured from human fecal matter, it may carry a risk of transmitting infectious agents. In clinical trials, the overall estimated rate of success in preventing recurrent CDI through eight weeks was significantly higher in the Rebyota group (70.6%) than in the placebo group (57.5%).³ Rebyota launch and price are pending.
• Rezlidhea^® (olutasidenib): Forma Therapeutics’ Rezlidhea was approved by the FDA for use in certain patients with relapsed or refractory (R/R) acute myeloid leukemia(AML). Specifically, the drug is approved for use in patients who have R/R AML with a susceptible isocitrate dehydrogenase 1 (IDH1) mutation as detected by an FDA-approved test. The FDA also approved the Abbott RealTime IDH1 Assay to select patients for treatment. Rezlidhea is an oral inhibitor of mutated IDH1 that has been designed to bind and inhibit mutated IDH1 to reduce hydroxyglutarate levels and restore cellular differentiation of myeloid cells. Rezlidhea met its primary endpoint of a composite of a complete remission (CR) plus a complete remission with partial hematological recovery (CRh) in its pivotal clinical trial. Results from the trial demonstrated a 35% CR+CRh rate in mIDH1 R/R AML patients, with a median duration of response of 25.9 months. The median time to CR or CRh was 1.9 months.⁴ Rezlidhia has launched with an AWP of $644 per capsule.
• Krazati^® (adagrasib): The FDA has granted accelerated approval of Mirati Therapeutics’ Krazati, the inhibitor of the RAS GTPase family as oral monotherapy for second-line treatment of advanced non-small cell lung cancer (NSCLC) patients harboring the KRAS G12C mutation following at least one prior systemic therapy. Krazati was approved based on the Phase 2 cohort KRYSTAL-1 study which demonstrated an objective response rate (ORR) of 43% with 80% of patients achieving disease control. The median duration of response (DOR) was 8.5 months.⁵ Krazati launch and price are pending.

New Indications

• Rylaze^® (asparaginase erwinia chrysanthemi (recombinant)- rywn): The FDA approved Jazz Pharmaceuticals’ Rylaze new dosing regimen for the asparagine specific enzyme for administration on Monday, Wednesday and Friday as component of a multi-agent chemotherapy regimen for treatment of acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma (LBL) in adult and pediatric patients 1 month or older who have developed hypersensitivity to E coli-derived asparaginase.
• Imjudo^® (tremelimumab-actl): AstraZeneca’s Imjudo has been approved by the FDA to expand its indication for use in combination with AZ’s PD-L1 inhibitor durvalumab (Imfinzi) and platinum-based chemotherapy for treatment of adults with metastatic non-small cell lung cancer (NSCLC) with no sensitizing EGFR mutation or anaplastic lymphoma kinase (ALK) genomic tumor aberrations.
• Imfinzi^® (durvalumab): AstraZeneca’s Imfinzi has been approved by the FDA to include the treatment of adults with metastatic non-small cell lung cancer (NSCLC) with no sensitizing EGFR mutation or anaplastic lymphoma kinase (ALK) genomic tumor aberrations.
• Tecentriq^® (atezolizumab): Genentech’s Tecentriq received FDA approval for adult and pediatric patients 2 years of age and older with unresectable or metastatic alveolar soft part sarcoma.

December News

• “Johnson & Johnson unit Janssen sued Amgen over the company’s proposed biosimilar to its megablockbuster Stelara (ustekinumab), after Amgen said it was ready to launch next May or as soon as the FDA signs off on it. If Amgen carries through with that plan, Janssen told the Delaware district court that the Thousand Oaks, CA-based company will infringe on at least two Janssen patents. The suit follows Amgen’s announcement in April that preliminary results from a Phase III study evaluating the efficacy and safety of its ustekinumab biosimilar, known as ABP 654, met its primary efficacy endpoint in adult patients with moderate-to-severe plaque psoriasis, demonstrating no clinically meaningful differences between ABP 654 and Stelara.”⁶
• “After more than a decade and a half in development, the FDA’s Cardiovascular and Renal Drugs Advisory Committee today voted 8-3 against approval of Cytokinetics’ heart failure drug. Adcomm members said the drug’s potential benefits did not seem to outweigh its risks, with panel members raising concerns about the drug’s safety and its limited efficacy. The drug, known as omecamtiv mecarbil (OM), has seen mixed clinical results, with a first Phase 3 readout from November 2020 hitting the primary endpoint of reducing the odds of hospitalization or other urgent care for heart failure by 8%. But it also missed a key secondary endpoint analysts had pegged as key to breaking into the market.”⁷
• “BioMarin Pharmaceutical Inc. announced advancements in the U.S. Food and Drug Administration (FDA) review of the Biologics License Application (BLA) of ROCTAVIAN™ (valoctocogene roxaparvovec AAV gene therapy) for adults with severe hemophilia A. The Company was recently notified by the FDA that after further consideration, at this time, the Agency no longer plans to hold an advisory committee meeting to discuss the BLA for ROCTAVIAN that is currently under review.  Previously, the FDA communicated to the Company that it did intend to hold an advisory committee meeting but did not specify a date.”⁸
• “Looking back, 2022 brought two key successful Phase 3 trials. In September, Eisai and Biogen announced lecanemab met its primary endpoint of slowing the rate of cognitive decline in a 1,906-patient Phase 3 study. Just last week, Anavex announced blarcamesine met its primary endpoint of slowing decline in a 509-patient Phase 2b/3 trial. However, 2022 was also full of bumps and controversies. In November, Roche announced its antibody, gantenerumab, missed the mark in the Phase 3 GRADUATE-1 and GRADUATE-2 studies. Meanwhile, Medicare announced in April it would severely restrict coverage of Aduhelm, shattering the sales prospects of what analysts once believed to be a multi-billion dollar drug. And over the summer, a report suggested data manipulation in studies backing the amyloid theory behind most current AD therapies. As sponsors work to make sense of 2022, here’s a look at three major questions that could shape AD drug development in 2023. Will Lilly’s donanemab break through? Will AD trials become more inclusive? Will there be new approaches to AD drug development?”⁹

References

1. https://www.fda.gov/news-events/press-announcements/fda-approves-first-drug-can-delay-onset-type-1-diabetes
2. https://www.ajmc.com/view/fda-panel-supports-approving-teplizumab-to-delay-type-1-diabetes
3. https://www.statnews.com/2022/11/30/fda-approves-first-microbiome-drug/
4. https://www.rigel.com/investors/news-events/press-releases/detail/349/rigel-announces-u-s-fda-approval-of-rezlidhia
5. https://www.prnewswire.com/news-releases/mirati-therapeutics-announces-us-fda-accelerated-approval-of-krazati-adagrasib-as-a-targeted-treatment-option-for-patients-with-locally-advanced-or-metastatic-non-small-cell-lung-cancer-nsclc-with-a-krasg12c-mutation-301700902.html
6. https://endpts.com/protecting-its-megablockbuster-janssen-challenges-amgens-stelara-biosimilar-ahead-of-planned-2023-launch/
7. https://endpts.com/fda-adcomm-votes-8-3-against-cytokinetics-potential-heart-failure-drug/
8. https://investors.biomarin.com/2022-11-23-BioMarin-Announces-Advancements-in-FDA-Review-of-ROCTAVIAN-TM-Valoctocogene-Roxaparvovec-for-Adults-with-Severe-Hemophilia-A
9. https://www.clinicaltrialsarena.com/features/alzheimers-2023/