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Monthly News Roundup - November 2022

FDA Approves Hemgenix, a Historic, One-Time Gene Therapy for Hemophilia B

In November, the U.S. Food and Drug Administration (FDA) approved CSL Behring’s Hemgenix (etranacogene dezaparvovec-drlb), an adeno-associated virus vector-based gene therapy indicated for the treatment of adults with hemophilia B. Hemgenix is administered as a single intravenous infusion and is given only once.

  • Hemophilia B is a rare, lifelong bleeding disorder caused by a single gene defect, resulting in insufficient production of factor IX, a protein primarily produced by the liver that helps to form blood clots. People with the condition are particularly vulnerable to bleeding in their joints, muscles, and internal organs, leading to pain, swelling, and joint damage.
  • Hemgenix is indicated for adults with hemophilia B who currently use factor IX prophylaxis therapy, have life-threatening hemorrhage or have repeated, serious spontaneous bleeding episodes. It allows people living with hemophilia B to produce their own factor IX, and can lower the risk of bleeding with a single dose. Typically, patients with hemophilia B have to adhere to strict, expensive, lifelong infusion schedules of factor IX.
  • In the ongoing HOPE-B clinical trial, Hemgenix reduced the rate of annual bleeds and 94% of patients discontinued factor IX infusions. Seven to 18 months after Hemgenix, the mean adjusted annualized bleeding rate (ABR) for all bleeds was reduced by 54%.
  • Hemgenix works by supplying a noninfectious viral vector (AAV5) to carry genetic DNA instructions to the liver, where factor IX proteins are then generated. These genetic instructions remain in the target cells, but generally do not become a part of a person’s own DNA.
  • The most common side effects (incidence ≥5%) were liver enzyme elevations, headache, elevated levels of a certain blood enzyme, flu-like symptoms, infusion-related reactions, fatigue, nausea and feeling unwell.
  • The single dose therapy is priced at $3.5 million, according to CSL Behring.

Libtayo + Chemotherapy Cleared as First-line Therapy for Advanced NSCLC

Lung cancer is the leading cause of cancer death worldwide. In November, the FDA cleared Regeneron’s Libtayo (cemiplimab-rwlc), a programmed death receptor-1 (PD-1) blocking antibody, plus platinum-based chemotherapy as first-line treatment of adults with advanced non-small cell lung cancer (NSCLC) with no EGFR, ALK or ROS1 aberrations. Patients must not be candidates for surgery or chemotherapy with radiation, but can be treated with this combination irrespective of PD-L1.

  • FDA approval was based on superior survival outcomes of Libtayo + chemotherapy, compared to chemotherapy alone in 466 patients. In the Phase 3 EMPOWER-Lung 3 trial, Libtayo + chemotherapy demonstrated a marked increase in overall survival (OS) - a median of 22 months versus 13 months with chemotherapy alone. The trial was stopped early due to a significant improvement in OS, the primary endpoint.
  • Other Libtayo + chemotherapy endpoints compared to chemotherapy alone (respectively) included: an 8-month versus 5 month median progression-free survival (PFS); a 43% versus 23% overall response rate; and a 16-month (range: 2 to 19+) versus 7 months (range: 2 to 19+) median duration of response (DoR).
  • The recommended dose of Libtayo is 350 mg IV over 30 minutes every 3 weeks until disease progression or unacceptable toxicity.
  • Warnings include immune-mediated adverse reactions, which may be severe or fatal, and can occur in any organ system or tissue. Serious adverse reactions occurred in 25% of patients, with treatment discontinuations due to adverse reactions in 5% and fatal adverse reactions in 6%.
  • The most common side effects of Libtayo (when added to chemotherapy) included: alopecia (hair loss), musculoskeletal pain, nausea, fatigue, peripheral neuropathy (pain, weakness, and numbness from nerve damage, usually in the hands and feet) and decreased appetite.
  • Libtayo is also approved to treat cutaneous squamous cell carcinoma (CSCC), basal cell carcinoma (BCC), and as a single agent for the first-line treatment of adult patients with NSCLC whose tumors have high PD-L1 expression.

AstraZeneca’s Imfinzi + Imjudo + Chemotherapy OK’d for Metastatic NSCLC

For patients with metastatic non-small cell lung cancer (NSCLC), only about 8% will live more than five years after their diagnosis. In response, the FDA has approved AstraZeneca’s Imfinzi (durvalumab) in combination with Imjudo (tremelimumab-actl) plus platinum-based chemotherapy for adults with stage IV metastatic NSCLC. Patients should have no EGFR or ALK aberrations. Metastatic cancer has spread in the body from its original site.

  • Imfinzi is a PD-L1 blocking antibody immunotherapy and Imjudo is an CTLA-4 blocking antibody immunotherapy. Approval was based on the POSEIDON randomized, open label, Phase III study with 1,013 patients with metastatic NSCLC. Patients were treated first-line with a limited course of five cycles of Imjudo added to Imfinzi plus four cycles of platinum-based chemotherapy. The primary outcome measures were progression free survival (PFS) and overall survival (OS) compared to platinum-based chemotherapy alone.
  • Results showed a significant median OS of 14 months with Imfinzi / Imjudo / platinum-based chemotherapy vs. 11.7 months with chemotherapy alone (a 23% reduction in the risk of death). An estimated 33% of patients were alive at two years versus 22% for chemotherapy alone. The median PFS was 6.2 months with Imfinzi / Imjudo / platinum-based chemotherapy vs. 4.8 months with chemotherapy alone.
  • The intravenous (IV) regimen in patients weighing at least 30 kg is Imfinzi 1,500 mg every 3 weeks in combination with Imjudo 75 mg and platinum-based chemotherapy for 4 cycles, and then administer Imfinzi 1,500 mg every 4 weeks as a single agent with histology-based pemetrexed maintenance therapy every 4 weeks, and a fifth dose of Imjudo 75 mg in combination with Imfinzi dose 6 at week 16. Dosing is weight-based in patients less than 30 kg as outlined in the label.
  • Warnings include immune-mediated adverse reactions, which may be severe or fatal, and can occur in any organ system or tissue. The most common side effects (≥ 20%) include: nausea, fatigue, musculoskeletal pain, decreased appetite, rash, and diarrhea.

Tzield Cleared to Delay the Onset of Clinical Type 1 Diabetes

Over 1.8 million Americans have type 1 diabetes (T1D), an autoimmune disease caused by the destruction of pancreatic beta cells. This past month the FDA approved Provention Bio’s Tzield (teplizumab-mzwv), a CD3-directed antibody indicated to delay the onset of Stage 3 T1D in adults and children aged 8 years and older with Stage 2 T1D. Tzield is the first disease-modifying therapy in T1D.

  • Stage 3 type 1 diabetes (T1D) is associated with significant health risks, including diabetic ketoacidosis, which can be life threatening. Patients who progress to Stage 3 T1D eventually require insulin injections for life.
  • In the TN-10 placebo-controlled study, 67 Stage 2 T1D patients ages 8 to 49 ( with 72% under the age of 18) received either a single 14-day course of teplizumab or placebo by IV infusion. Researchers evaluated the time to delay to Stage 3 T1D (clinical T1D) diagnosis, defined by the presence of two or more T1D-related autoantibodies and altered blood sugar levels. Tzield delayed the median onset of Stage 3 T1D by a statistically significant 25 months compared to placebo (50 months in the Tzield group vs. 25 months in the placebo group).
  • Tzield is administered by intravenous infusion (over a minimum of 30 minutes) once daily for 14 consecutive days. The dose is based on body surface area and premedication is required for the first 5 doses.
  • Serious warnings include cytokine release syndrome (CRS), infections, low white blood cell counts (lymphopenia), and sudden allergic reactions. Administer all age-appropriate vaccinations prior to starting therapy.
  • Common side effects (>10%) include: decreased white blood cell counts (lymphopenia, leukopenia), rash and headache.

Elahere Gains Accelerated Approval to Treat Platinum-Resistant Ovarian Cancer

Elahere (mirvetuximab soravtansine-gynx), from ImmunoGen, has received FDA-approval to treat adults with FRα positive ovarian, fallopian tube, or primary peritoneal cancer, who have received 1 to 3 prior systemic treatment regimens. These patients have not responded to or are no longer responding to treatment with platinum-based chemotherapy. Eligible patients are determined via a companion diagnostic tool, the VENTANA FOLR1 RxDx IHC Assay.

  • Elahere is a first-in-class antibody-drug conjugate (ADC) that works by targeting folate receptor-alpha (FRα), a cell-surface protein highly expressed in ovarian cancer. It is composed of a folate receptor alpha-binding antibody, cleavable linker, and the maytansinoid payload DM4, a potent tubulin inhibitor designed to kill the targeted cancer cells. It is the first FDA-approved ADC for platinum-resistant disease.
  • Elahere approval was based on the pivotal SORAYA trial with 106 patients. Outcomes included objective response rate (ORR), the primary objective, and duration of response (DoR) data, a key secondary objective. Elahere demonstrated an ORR of 31.7%, including five complete responses, and the median DOR was 6.9 months.
  • Elahere carries a Boxed Warning, the FDA’s most prominent warning, for severe ocular toxicity, including visual impairment, keratopathy, dry eye, photophobia, eye pain, and uveitis.
  • The most common side effects (in at least 20% of patients) included: vision impairment, fatigue, increased liver enzymes, nausea, cornea damage, abdominal pain, decreased lymphocytes, and peripheral neuropathy, among others.
  • The full approval of Elahere may depend upon the clinical benefit outcomes in the confirmatory MIRASOL trial, with top-line data expected in early 2023.

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