Specialty Pipeline Update: April 2022

This monthly 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 article for pipeline information on traditional drugs.

New Drug Information

• Opdualag™ (nivolumab and relatlimab-rmbw) injection, for intravenous use: The U.S. Food and Drug Administration (FDA) approved BMS’ Opdualag (nivolumab and relatlimab-rmbw) for adult and pediatric patients 12 years of age or older with unresectable or metastatic melanoma as a fixed-dose dual immunotherapy single intravenous infusion administered every 4 weeks.[1]^,[2] Nivolumab (also available as BMS’ Opdivo) is a PD-1 inhibitor and relatlimab is a LAG-3-blocking antibody. The approval was based on the phase 2/3 RELATIVITY-047 trial (N=714) which demonstrated that Opdualag more than doubled the median progression-free survival (PFS), the primary endpoint, when compared to nivolumab monotherapy: 10.1 months versus 4.6 months; HR 0.75; 95% CI 0.62 to 0.92, p=0.0055. Opdualag will compete with the combination of Opdivo + Yervoy (ipilimumab; BMS). Using cross-trial comparison, Opdivo + Yervoy efficacy may be higher (11.5 months of PFS in CHECKMATE-067) but Opdualag may have the safety advantage (Grades 3 or 4 adverse events 55% for Opdivo-Yervoy in CHECKMATE-067 vs 19% for Opdualag in RELATIVITY-047). In terms of pricing, the annual list price for Opdualag is ~$329,000 while an average annual list price for Opdivo + Yervoy regimen is ~$179,000. (Note: Only 4 doses of Yervoy, in combination with Opdivo, are recommended for unresectable or metastatic melanoma. After 4 doses, Opdivo is administered as a single agent until disease progression or unacceptable toxicity.)[3]
• Vijoice™ (alpelisib) tablets: Novartis’ Vijoice (alpelisib) received accelerated approval from the FDA for the treatment of adult and pediatric patients 2 years of age and older with severe manifestations of PIK3CA-related overgrowth spectrum (PROS) who require systemic therapy.[4] PROS represents overgrowth conditions caused by PIK3CA with an estimated prevalence of 14 per million or about 5,000 people in the U.S. Vijoice is an oral kinase inhibitor that works by inhibiting the PI3K pathway. Vijoice’s accelerated approval was based on a retrospective chart review study, EPIK-P1, that demonstrated patients treated with Vijoice orally once daily experienced reduced target lesion volume and improvement in symptoms and manifestations related to PROS. At week 24, 27% (10/37) achieved a confirmed response to treatment with Vijoice, which was the primary endpoint defined as 20% or greater reduction in the sum of PROS target lesion volume.[5] Alpelisib is also approved as Novartis’ Piqray for the treatment of certain breast cancers which has a list price of approximately $186,000 annually, while Vijoice will cost approximately $390,000 annually. There are no other FDA approved medications to treat PROS, management varies by patient, but surgery and radiologic embolization are common.
• Alymsys (bevacizumab-maly) injection, for intravenous use: The FDA approved Amneal’s Alymsys (bevacizumab-maly), a biosimilar referencing Genentech’s Avastin. This is the third bevacizumab biosimilar approved in the U.S joining Pfizer’s Zirabev^® and Amgen’s Mvasi^®.[6] For the 12 months ended February 2022, U.S. annual sales for bevacizumab were $2.6 billion, $1.6 billion of which represented biosimilar sales according to IQVIA^®.
• Ztalmy (ganaxolone) oral suspension: The FDA approved Marinus’ Ztalmy oral suspension for seizures associated with CDKL5 deficiency disorder (CDD) in patients aged 2 and older. Ztalmy is the first approved treatment for CDD, a rare genetic disorder characterized by early-onset and difficult-to-control seizures. The phase 3 MARIGOLD double-blind placebo-controlled trial (n=101) demonstrated that patients treated with weight-based dosing of Ztalmy orally three times daily showed a median 30.7% reduction in 28-day motor seizure frequency compared to 6.9% in the placebo group (p=0.0036), achieving the trial’s primary endpoint. Ztalmy is expected to launch in July 2022 through a designated specialty pharmacy following scheduling by the U.S. Drug Enforcement Administration (DEA). Marinus will target patients with CDD aged 2 to 21 years old who aren’t responding to current treatment which they estimate to be about 2,000 people in the U.S.[7]^,[8] The average annual wholesale acquisition cost (WAC) per Marinus will be $133,000.

New Indications

• Lynparza^® (olaparib): AstraZeneca’s Lynparza received FDA approval for the adjuvant treatment of adult patients with deleterious or suspected deleterious germline BRCA-mutated human epidermal growth factor receptor 2 (HER2)-negative high-risk early breast cancer who have been treated with neoadjuvant of adjuvant chemotherapy.
• Rinvoq^® (upadacitinib): AbbVie’s Rinvoq received FDA approval for the treatment of adults with moderately to severely active ulcerative colitis who have had an inadequate response or intolerance to one or more tumor necrosis factor (TNF) blockers.
• Yescarta (axicabtagene ciloleucel): The FDA approved Kite’s Yescarta for adults patients with large B-cell lymphoma (LBCL) that is refractory to first-line chemoimmunotherapy or relapses within 12 months of first-line chemoimmunotherapy.

April News

• “With these limitations in mind, current evidence does suggest that the drugs of interest [sotrovimab, molnupiravir, Paxlovid^®, fluvoxamine] reduce hospitalizations among patients with mild-to-moderate COVID-19 who are at high risk of progression to severe disease. Numbers of deaths in the pivotal trials are too small to draw firm conclusions.”[9]
• “Composed of neuroscience and drug development experts, the 10-person advisory committee on Wednesday voted 6 to 4 against the medicine, named AMX0035 and developed by the Cambridge, Massachusetts-based biotechnology company Amylyx Pharmaceuticals.”[10]
• “TG Therapeutics, Inc., announced that the Company has voluntarily withdrawn the pending Biologics License Application (BLA)/supplemental New Drug Application (sNDA) for the combination of ublituximab and UKONIQ® (umbralisib) (combination referred to as U2) for the treatment of adult patients with chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL).”[11]
• “The FDA has issued a Complete Response Letter (CRL) to Akebia Therapeutics regarding the New Drug Application (NDA) for vadadustat, an investigational therapy for anemia due to chronic kidney disease (CKD).”[12]

[1] Bristol Myers Squibb – U.S. Food and Drug Administration Approves First LAG-3-Blocking Antibody Combination, Opdualag™ (nivolumab and relatlimab-rmbw), as Treatment for Patients with Unresectable or Metastatic Melanoma (bms.com)

[2] Bristol Myers’ Opdivo combo Opdualag scores FDA approval in melanoma, opens 3rd immune checkpoint drug class | Fierce Pharma

[3] YERVOY U.S. Prescribing Information (bms.com)

[4] FDA approves Novartis Vijoice® (alpelisib) as first and only treatment for select patients with PIK3CA-Related Overgrowth Spectrum (PROS) | Novartis

[5] vijoice.pdf (novartis.us)

[6] Amneal Achieves Second U.S. Biosimilars Approval with ALYMSYS® (bevacizumab-maly) | Business Wire

[7] Marinus Pharmaceuticals, Inc. – Marinus Pharmaceuticals Announces FDA Approval of ZTALMY® (ganaxolone) for CDKL5 Deficiency Disorder

[8] FDA approves new epilepsy drug, handing Marinus a long-awaited victory | BioPharma Dive

[9] ICER_COVID_19_Evidence_Report_032822.pdf

[10] FDA advisers narrowly side against an experimental ALS drug, likely lowering its approval chances | BioPharma Dive

[11] TG Therapeutics Announces Voluntary Withdrawal of the (globenewswire.com)

[12] FDA Says No to Vadadustat Approval Due to Safety Concerns – Hematology Advisor