Sanofi drops out of breast cancer drug race after another failed attempt - MedCity News

Hormonal therapies are well established in the treatment of breast cancer, working by blocking or reducing the levels of hormones that fuel tumor growth. If the disease progresses, the next line of therapy involves an injectable drug that specifically targets the estrogen receptor on the cancer cells. Several big pharmaceutical companies are trying to develop drugs that work the same way, but in a more convenient pill formulation. Stemline Therapeutics beat them all to win the first FDA approval for an oral drug in this drug class.

Friday regulatory decision for the drug, elacestrant, covers postmenopausal women or older men whose breast cancer has progressed after at least one line of hormone therapy. Stemline, a New York-based subsidiary of Italian company Menarini Group, will market its new once-daily pill under the name “Orserdu.”

The Stemline drug is what is called a Selective Estrogen Receptor Degrader (SERD). The first such drug to reach the market was Faslodex, an AstraZeneca cancer drug that became a blockbuster after Approval since 2002. But generic versions launched in recent years have eaten into sales of Faslodex, which total $431 million in 2021. AstraZeneca’s brand-name drug and subsequent generic SERDs are administered as intramuscular injections in the buttocks.

The FDA’s decision on Orserdu was based on the results of a phase 3 trial that included 478 patients with advanced breast cancer that was classified as estrogen receptor (ER) positive and HER2 negative. The total enrollment included 228 patients whose breast cancer also had a mutation called ESR1. All study participants had cancer that had progressed after one or two previous hormone therapies. Patients were randomly assigned to receive the study drug or standard hormonal therapies, including Faslodex.

The main goal of the study was to measure progression-free survival, which is how long patients lived without their cancer getting worse. In patients with ESR1 mutations, median progression-free survival was 3.8 months in the Orserdu arm versus 1.8 months in the control arm. The FDA said that an exploratory analysis in patients whose cancer did not have an ESR1 mutation showed that the improvement seen in all randomized patients was mainly due to the results in patients with ESR1 mutations. The FDA’s nod for Orserdu covers only those patients. This mutation should be detected by a companion diagnostics from Guardant Healthwhich also won FDA approval.

“ESR1 mutations are a known driver of resistance to standard endocrine therapy and have so far been difficult to treat,” he said in a prepared statement. “The approval of elacestrant is welcome as it offers a new option for patients with ER positive, HER2 negative metastatic breast cancer.”

The most common side effects seen in the studies included nausea, muscle aches, higher cholesterol, increased liver enzyme levels, and fatigue. These adverse reactions are comparable to reactions to Faslodex.

Menarini acquired global rights to Orserdu in 2020 from Radius Health, which is leading clinical development of the small molecule. The approval of Orserdu means that Radius will receive core payments as well as royalties from sales of the drug. Menarini is responsible for the further development of the drug in other markets.

The approval of Orserdu follows clinical trials of oral SERDs by major pharmaceutical companies. Last March, Sanofi reported on Phase 2 failure of the drug candidate amcenestrant in advanced ER-positive, HER2-negative breast cancer. Sanofi withdrew from the oral SERD race last summer after a Phase 3 trial of this drug as first-line therapy. Meanwhile, Roche’s oral SERD, giredestrant, failed its phase 2 trial. AstraZeneca is still looking into an oral SERD called camisestrant. Last October, the pharmaceutical giant announced Phase 2 results showed that both doses of the drug resulted in an improvement in progression-free survival compared with Faslodex treatment.

Two other recent regulatory approvals have expanded treatment options for cancer patients. Here is a summary of those decisions:

Eli Lilly Grants FDA Approval for Mantle Cell Lymphoma

Eli Lilly’s pirtobrutinib, a cancer drug added to its pipeline by Acquisition of Loxo Oncology for $8 billion in 2019, it is now FDA approved to treat a rare blood cancer called mantle cell lymphoma (MCL). Lilly will market the pill as “Jaypirca.”

MCL is a cancer of B lymphocytes, a type of white blood cell. It is named after the mantle zone at the outer edge of the lymph nodes, where this type of cancer often begins. Jaypirca is indicated for those whose MCL has relapsed or failed to respond to at least two lines of systemic therapy, including a class of drugs that block Bruton’s tyrosine kinase (BTK), an enzyme that plays a role in the spread of blood cancers.

Jaypirca is a non-covalent or reversible inhibitor of BTK. This ability means that it can restore BTK inhibition in MCL patients who have previously been treated with a covalent BTK inhibitor. The new Lilly drug provides another treatment option for those who cannot tolerate BTK inhibitors, as well as those whose cancer progresses during treatment with a covalent BTK-blocking drug. Michael Wang, a professor of lymphoma and myeloma at the University of Texas MD Anderson Cancer Center, said in a prepared statement that Jaypirca may extend the length of time patients can benefit from a therapy that works by inhibiting BTK.

The FDA’s decision on Jaypirca was an accelerated approval. Lilly said the confirmatory study needed for such rapid approvals currently involves patients.

Merck’s Keytruda is approved as an adjuvant therapy for lung cancer

Keytruda, Merck’s immunotherapy megablockbuster, whose long list of approved uses includes several in non-small cell lung cancer (NSCLC), scored another. The agency approved adjuvant medicine, a treatment given after a primary treatment, such as surgery, to prevent the cancer from coming back. The FDA decision allows the Merck drug to be used after surgical removal of NSCLC tumors classified by size as stage Ib, II or IIIA.

This latest approval of Keytruda is based on the results of a placebo-controlled phase 3 study that enrolled 1,177 patients, the majority of whom received adjuvant chemotherapy. These patients were randomly assigned to receive intravenously infused Keytruda or a placebo administered every three weeks for up to a year.

The main aim was to measure disease-free survival – how long patients live without signs or symptoms of cancer. The FDA said the trial met the primary objective in the overall study population. In patients who had previously received adjuvant chemotherapy, median disease-free survival was 58.7 months compared with 34.9 months in the placebo arm. The adjuvant approval of Keytruda covers patients with NSCLC who received adjuvant chemotherapy after surgery.

Public domain image from the National Cancer Institute

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