FDA approves Necitumumab for Squamous NSCLC

Posted by Dr. Guneet Walia on November 24th, 2015

The US FDA today approved Necitumumab or Portrazza in combination with two forms of chemotherapy – gemcitabine (Gemzar) and cisplatin (Platinol)- for the treatment of advanced, metastatic squamous non-small cell lung cancer (NSCLC) patients who have not been previously treated for their advanced lung cancer.

Mechanism of Action: Necitumumab or Portrazza is a human monoclonal antibody that binds and blocks EGFR (Epidermal Growth Factor Receptor), a protein commonly found on squamous NSCLC tumors.

Clinical Trial: The approval of Necitumumab is based off the data from the multi-center, randomized phase III SQUIRE clinical trial in 1093 patients that compared Necitumumab+ gemcitabine+ cisplatin (545 patients) vs. gemcitabine+ cisplatin (548 patients). These results showed that the addition of Necitumumab to the chemotherapy combination conferred an overall survival benefit of 1.6 months, equivalent to a 16% reduction in the risk of death. Patients on the Necitumumab+ chemo combination had a median overall survival of 11.5 months compared to 9.9 months for patients receiving only chemotherapy.

In July 2015, the FDA’s Oncology Drugs Advisory Committee panel recommended for Necitumumab approval, stating that even though survival benefits of Necitumumab were modest, these were clinically significant and would provide an option to a lung cancer patient subset that currently doesn’t have many treatment options.

Non-small cell lung cancer accounts for over 85% of all lung cancer diagnoses, and is further divided into 2 sub-categories- squamous NSCLC (accounts for 30% of all lung cancer cases) and non-squamous NSCLC (includes adenocarcinoma). Today’s approval of Necitumumab is only for the squamous NSCLC indication. This agent does not show activity in the non-squamous NSCLC population as was observed in the large INSPIRE trial that compared the Necitumumab+ pemetrexed+ cisplatin combination vs. pemetrexed+ cisplatin.

Side Effects: The FDA notes that the most common side effects of Portrazza are skin rash and magnesium deficiency (hypomagnesemia), which can cause muscular weakness, seizures, irregular heartbeats and can be fatal. Necitumumab comes with a black box warning to alert health care providers of serious risks of treatment with Portrazza, that include cardiac arrest and sudden death due to blood clots, as well as hypomagnesemia.

Price: Though the price for Necitumumab has not been formally announced by its manufacturers, a study in the Journal of the American Medical Association (JAMA) Oncology earlier this year used Necitumumab as an example for establishing value-based cost for oncology drugs.

According to the authors of this JAMA Oncol. paper, “value-based pricing links the price of a drug to the benefit it provides and is a novel method to establish prices for new treatments”.

Using mathematical modeling that took into account survival benefits as well as adverse side effects of Necitumumab seen in the SQUIRE trial, the authors evaluated incremental cost-effectiveness ratios for the use of this drug across a range of values for its cost. This modeling suggests that a value-based cost for Necitumumab should range from $563- $1309 per cycle. It remains to be seen if this will indeed be the price that is set for Necitumumab by its manufacturers.

Access: Portrazza is manufactured by Eli Lilly. Lilly has assistance programs for eligible patients receiving Portrazza, including a co-pay program that allows qualified patients to pay no more than $25 per dose. For more details, patients, physicians and pharmacists may reach out to the company at 1-800-LillyRx (1-800-545-5979).

Ongoing Clinical Development: Necitumumab is currently being investigated in clinical trials in patients with NSCLC and in a combination clinical trial in immuno-oncology.

Squamous NSCLC accounts for 30% of all lung cancer cases and is a difficult to treat form of the disease, with 5-year survival rates for patients with metastatic disease being less than 5%. Effective treatment options are needed for this disease subset of lung cancer, and this approval by the FDA is a promising step in that direction.

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