FDA Approves Companion Genetic Diagnostic Test for Erlotinib [Tarceva] in NSCLC

May 16, 2013

May 14, 2013 – The US Food and Drug Administration (FDA) today announced the approval of the cobas EGFR Mutation Test, a companion diagnostic for the cancer drug Erlotinib (Tarceva). This is the first FDA-approved companion diagnostic that can detect epidermal growth factor receptor (EGFR) gene mutations, which are present in approximately 10% of non-small cell lung cancers (NSCLCs).

The approval of this test comes at the same time as an expanded indication for Erlotinib (Tarceva). The FDA has also announced a labeling change for Erlotinib (Tarceva), and the drug is now indicated for first-line use in patients with metastasized NSCLC that tests positive for EGRF mutations. Until now, the official indication was second- or third-line use in advanced NSCLC.

“The approval of the cobas EGFR Mutation Test will allow physicians to identify non-small cell lung cancer patients who are candidates for receiving Erlotinib (Tarceva) as first-line therapy,” said Alberto Gutierrez, PhD, director of the Office of In Vitro Diagnostics and Radiological Health in the FDA’s Center for Devices and Radiological Health, in a statement. “Companion diagnostics play an important role in determining which therapies are the safest and most effective for a particular patient.”

The safety and effectiveness of the cobas EGFR Mutation Test was established with clinical data showing progression-free survival in NSCLC patients with specific types of EGFR mutations (exon 19 deletions or exon 21 L858R substitution mutations) for 10.4 months when they received Erlotinib (Tarceva) treatment, compared with 5.4 months for those who received standard therapy.

In the United States, Erlotinib (Tarceva) is currently the only drug available for use in EGFR-positive NSCLC, although elsewhere in the world, another similar drug is widely used: Gefitinib (Iressa). A third drug in this class of EGFR tyrosine kinase inhibitors (TKIs), Afatinib (Tomtovok, by Boehringer Ingelheim), is close to approval, with an FDA decision expected in July 2013. Afatinib will also have its own companion diagnostic test (Therascreen EGFR PCR Kit, from Qiagen).

Using an EGFR TKI in the first-line treatment of EGFR-mutated NSCLC is recommended by several clinical guidelines, including the American Society of Clinical Oncology.

Patient outcomes are significantly better when compared with chemotherapy, so much so that it “would be a tragedy not to use” an EGFR inhibitor in EGFR-positive patients, according to one expert in the field, Edward Kim, MD, PhD, assistant professor of medicine and director of clinical operations at the University of Texas MD Anderson Cancer Center, in Houston. To not know whether the tumor is mutation-positive is not acceptable anymore, he added.

However, testing for mutations is not yet routine, and there are difficulties with obtaining lung cancer samples of sufficient size and quality, as well as disagreement over which is the best method for obtaining such samples, as recently reported by Medscape Medical News. In addition, there are issues with the costs of such testing, as outlined in a comment from a surgeon is response to that article.

The cobas EGFR Mutation Test is manufactured by the Roche Molecular Systems. Erlotinib is comarketed by California-based Genentech, a member of the Roche Group and OSI Pharmaceuticals.


Ivacaftor [Kalydeco] approved by FDA to treat the rare G551D mutant positive form of cystic fibrosis

February 3, 2012

February 03, 2012 – From a press release by the FDA, we just learn about e new success of the principle of personalized medicine. Please read the original article below:

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The U.S. Food and Drug Administration today approved Kalydeco (ivacaftor) for the treatment of a rare form of cystic fibrosis (CF) in patients ages 6 years and older who have the specific G551D mutation in the Cystic Fibrosis Transmembrane Regulator (CFTR) gene.

CF is a serious genetic disorder affecting the lungs and other organs that ultimately leads to an early death. It is caused by mutations (defects) in a gene that encodes for a protein called CFTR that regulates ion (such as chloride) and water transport in the body. The defect in chloride and water transport results in the formation of thick mucus that builds up in the lungs, digestive tract and other parts of the body leading to severe respiratory and digestive problems, as well as other complications such as infections and diabetes.

CF, which affects about 30,000 people in the United States, is the most common fatal genetic disease in the Caucasian population. About 4 percent of those with CF, or roughly 1,200 people, are believed to have the G551D mutation.

“Kalydeco is an excellent example of the promise of personalized medicine – targeted drugs that treat patients with a specific genetic makeup,” said FDA Commissioner Margaret A. Hamburg, M.D. “The unique and mutually beneficial partnership that led to the approval of Kalydeco serves as a great model for what companies and patient groups can achieve if they collaborate on drug development.”

The FDA reviewed and approved Kalydeco in approximately three months under the agency’s priority review program that is designed to expedite the review of drugs. The priority review program uses a six-month review, instead of the standard 10 months, for drugs that may offer significant advances in treatment over available therapy.

Kalydeco was approved ahead of the drug’s April 18, 2012 prescription user fee goal date and is designated as an orphan drug, which identifies the disease as affecting fewer than 200,000 people in the United States.

In patients with the G551D mutation, Kalydeco, a pill taken two times a day with fat-containing food, helps the protein made by the CFTR gene function better and as a result, improves lung function and other aspects of CF such as increasing weight gain.

“Kalydeco is the first available treatment that targets the defective CFTR protein, which is the underlying cause of cystic fibrosis,” said Janet Woodcock, M.D., director of the FDA’s Center for Drug Evaluation and Research. “This is a breakthrough therapy for the cystic fibrosis community because current therapies only treat the symptoms of this genetic disease.”

Two 48-week, placebo-controlled clinical studies involving 213 patients, one in patients ages 12 years and older and another in patients ages 6 years to 11 years, were used to evaluate the safety and efficacy of Kalydeco in CF patients with the G551D mutation. In both studies, treatment with Kalydeco resulted in significant and sustained improvement in lung function.

Kalydeco is effective only in patients with CF who have the G551D mutation. It is not effective in CF patients with two copies of the F508 mutation in the CFTR gene, which is the most common mutation that results in CF. If a patient’s mutation status is not known, an FDA-cleared CF mutation test should be used to determine whether the G551D mutation is present.

The most common side effects of Kalydeco include upper respiratory tract infection, headache, stomach ache, rash, diarrhea, and dizziness.


Drug Safety Communication on Brentuximab Vedotin [Adcetris] – Progressive Multifocal Leukoencephalopathy (PML) and Pulmonary Toxicity

January 17, 2012

January 16, 2012 – The American Food and Drug Administration ( FDA) released on January 13, 2012 the following drug safety communication:

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ISSUE: FDA notified healthcare professionals that two additional cases of progressive multifocal leukoencephalopathy (PML), a rare but serious brain infection that can result in death, have been reported with the lymphoma drug Adcetris (brentuximab vedotin). Due to the serious nature of PML, a new Boxed Warning highlighting this risk has been added to the drug label.

In addition, a new Contraindication warning was added against use of Adcetris with the cancer drug bleomycin due to increased risk of pulmonary (lung) toxicity.

The signs and symptoms of PML may develop over the course of several weeks or months. They may include changes in mood or usual behavior, confusion, thinking problems, loss of memory, changes in vision, speech, or walking, and decreased strength or weakness on one side of the body.

BACKGROUND: Adcetris (brentuximab vedotin) is used to treat Hodgkin lymphoma and a rare lymphoma known as systemic anaplastic large cell lymphoma. At the time of Adcetris’ approval in August 2011, one case of PML was described in the Warnings and Precautions section of the label.

RECOMMENDATION: Patients who develop any signs and symptoms of PML should notify their healthcare professional immediately. Healthcare professionals should hold Adcetris dosing if PML is suspected and discontinue Adcetris if a diagnosis of PML is confirmed. See the Data Summary in the Drug Safety Communication for additional information.

Healthcare professionals and patients are encouraged to report adverse events or side effects related to the use of these products to the FDA’s MedWatch Safety Information and Adverse Event Reporting Program:

  • Complete and submit the report Online: www.fda.gov/MedWatch/report.htm1
  • Download form2 or call 1-800-332-1088 to request a reporting form, then complete and return to the address on the pre-addressed form, or submit by fax to 1-800-FDA-0178

 More Information as of 01/13/2012 – Drug Safety Communication3 – FDA]


Drug Safety Communication: Zoledronic Acid [Reclast] Associated with New Contraindication and Updated Warning on Kidney Impairment

September 2, 2011

September 01, 2011 – Risk factors for developing renal failure include underlying moderate to severe renal impairment, use of kidney-damaging (nephrotoxic) or diuretic medications at the same time as Zoledronic Acid [Reclast], or severe dehydration occurring before or after Zoledronic Acid [Reclast] is given. The risk of developing renal failure in patients with underlying renal impairment also increases with age.

The American Food and Drug Administration (FDA) has now notified healthcare professionals and patients of an update to the drug label for Zoledronic Acid [Reclast] regarding the risk of kidney failure. Cases of acute renal failure requiring dialysis or having a fatal outcome following Zoledronic Acid [Reclast] use have been reported to FDA. The revised label states that Zoledronic Acid [Reclast] is contraindicated in patients with creatinine clearance less than 35 mL/min or in patients with evidence of acute renal impairment. The label also recommends that healthcare professionals screen patients prior to administering Zoledronic Acid [Reclast] in order to identify at-risk patients.

The Zoledronic Acid [Reclast] Medication Guide for patients is being updated to contain information about the risk of severe kidney problems. In addition, the manufacturer of Zoledronic Acid [Reclast] will issue a Dear Healthcare Provider letter to inform healthcare professionals about this risk.

These labeling changes are being made to the Zoledronic Acid [Reclast] label only, although Zoledronic Acid, also sold as  [Zometa], is approved for treatment of cancer-related indications. Renal toxicity is already addressed in the Warnings and Precautions section of the [Zometa] label. Dose reductions for [Zometa] are provided for patients with renal impairment.

Recommendation:

Zoledronic Acid [Reclast] is contraindicated in patients with creatinine clearance less than 35 mL/min, or in patients with evidence of acute renal impairment. Healthcare professionals should screen patients prior to administering Zoledronic Acid [Reclast] in order to identify at-risk patients. Healthcare professionals should also monitor renal function in patients who are receiving Zoledronic Acid [Reclast].

Healthcare professionals and patients are encouraged to report adverse events or side effects related to the use of these products to the FDA’s MedWatch Safety Information and Adverse Event Reporting Program by completing and submitting the report online at www.fda.gov/MedWatch/report.htm. Alternatively, download the form or call +1-800-332-1088 to request a reporting form, then complete and return to the address on the pre-addressed form, or submit by fax to +1-800-FDA-0178.

Read here the MedWatch safety alert, including links to the Drug Safety Communication, including a Data Summary, and prescribing information.


The Pill: Possibly Increased Risk of Blood Clots with Birth Control Pills Containing Drospirenone

June 2, 2011

May 31, 2011 – The American Food and Drug Administration (FDA) has released today the following announcement aimed at physicians, family practices, and patients:

ISSUE: FDA is aware of two newly published studies that evaluated the risk of venous thromboembolism (VTE) in women who use birth control pills that contain drospirenone. The two recently published studies looked at whether there is a higher risk of blood clots in women taking birth control pills containing the progestin drospirenone when compared to similar women taking birth control pills containing a different progestin called levonorgestrel. These two new studies reported that there is a greater risk of VTE associated with birth control pills that contain drospirenone. This risk is reported to be up to 2 to 3 times greater than the risk of VTE associated with using levonorgestrel-containing pills. Other studies have not reported an increase in risk. The FDA is currently evaluating the conflicting results from these studies and will look at all currently available information to fully assess the risks and benefits of drospirenone-containing birth control pills. FDA will continue to communicate any new safety information to the public as it becomes available. Read the drug safety communication for more information on these studies.

BACKGROUND: Drospirenone is a type of female sex hormone called a progestin. Most birth control pills contain two types of hormones–estrogen and progestin. Birth control pills work by preventing the release of eggs from the ovaries (ovulation) and changing the cervical mucus and the lining of the uterus to prevent pregnancy. Brand names of drospirenone-containing products include Yaz (generics Gianvi and Loryna), Yasmin (generics Ocella, Syeda, and Zarah), Beyaz, and Safyral.

RECOMMENDATION: If your birth control pill contains drospirenone, do not stop taking it without first talking to your healthcare professional. Contact your healthcare professional immediately if you develop any symptoms of blood clots, including persistent leg pain, severe chest pain, or sudden shortness of breath. If you smoke and are over 35 years of age, you should not take combination oral contraceptives because they increase the risk that you could experience serious cardiovascular events, including blood clots.

Healthcare professionals and patients are encouraged to report adverse events or side effects related to the use of these products to the FDA’s MedWatch Safety Information and Adverse Event Reporting Program:

  • * Complete and submit the report Online: http://www.fda.gov/MedWatch/report.htm.
  • Download form1 or call 1-800-332-1088 to request a reporting form, then complete and return to the address on the pre-addressed form, or submit by fax to 1-800-FDA-0178.

More information can be found here:  [Drug Safety Communication– FDA] and  [Questions and Answers – FDA].


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