|May 2013, Volume XXIII, No. 3|
Regulatory & Legislative Highlights
By Deepen Joshi, Sunovion Pharmaceuticals
Isentress (raltegravir) has been approved by the FDA for use with other antiretroviral drugs for the treatment of HIV-1 infection for children and adolescents ages 2-18. The drug is part of a class of medications called HIV integrase strand transfer inhibitors that works by slowing the spread of HIV in the body. It was first approved for use in adult patients in October 2007, under FDA's accelerated approval program, which allows the agency to approve a drug to treat a serious disease based on clinical data showing that the drug has an effect on a surrogate endpoint that is reasonably likely to predict a clinical benefit to patients. Isentress does not cure HIV infection. Patients must stay on continuous HIV therapy to control HIV infection and decrease HIV-related illnesses. (Source: FDA Website, 21 December, 2011).
Prevnar 13, a pneumococcal 13-valent conjugate vaccine manufactured by Wyeth Pharmaceuticals, has been approved by the FDA for people ages 50 years and older to prevent pneumonia and invasive disease caused by the bacterium, Streptococcus pneumoniae. Pneumococcal pneumonia, caused when the bacterium Streptococcus pneumoniae infects the lungs, is the most common disease caused by this bacterium in adults. When the bacterium invades parts of the body that are normally free from germs, such as the blood or spinal fluid, the disease is considered "invasive."
Prevnar 13 is approved for use in children ages 6 weeks through 5 years for the prevention of invasive disease caused by 13 different serotypes of the bacterium Streptococcus pneumoniae and for the prevention of otitis media caused by seven of the serotypes of the bacterium. (Source: FDA Website, 30 December, 2011)
The FDA recently completed its recommendations for three user fee programs that will help speed safe and effective drugs and lower-cost generic drug and biosimilar biological products to patients. The recommendations were transmitted to Congress by Health and Human Services. The programs include the fifth authorization of the Prescription Drug User Fee Act (PDUFA) and new user fee programs for human generic drugs and biosimilar biological products.
Under a user fee program, industry agrees to pay fees to help fund a portion of the FDA's drug review activities while the FDA agrees to overall performance goals such as reviewing a certain percentage of applications within a particular time frame.
The proposed user fee programs for generic drugs and biosimilars are modeled on the successful PDUFA program. As a result of the continued investment of PDUFA resources, the United States now leads the world in first introduction of novel drugs.
The proposed new Generic Drug User Fee program would provide the FDA with needed funding at a time when generic drug applications are on the rise. Generic drug user fees would help ensure consumers timely access to safe, high-quality and effective generic drugs, which account for two-thirds of all prescriptions dispensed in the US.
The recommended user fee program for biosimilars includes fees for products in development to generate revenue in the near-term and to provide FDA with the resources needed to support development-phase meetings with sponsors of biosimilar biological product candidates. (Source: FDA Website, 13 January, 2012)
The FDA and representatives from the medical device industry have reached an agreement in principle on proposed recommendations for the third reauthorization of a medical device user fee program. The recommendations would authorize the FDA to collect $595 million in user fees over five years, plus adjustments for inflation.
Under a user fee program, industry agrees to pay fees to help fund a portion of the FDA's device review activities while the FDA agrees to overall performance goals such as reviewing a certain percentage of applications within a particular time frame.
FDA will develop a package of proposed recommendations and give the public an opportunity to comment before they are submitted to Congress. The date of the public meeting has yet to be determined. (Source: FDA Website, 01 February, 2012)
FDA Permits Marketing of First Test for Risk of Rare Brain Infection in Some People Treated With Tysabri
The FDA has allowed marketing of the first test to help determine the risk for a rare brain infection called progressive multifocal leukoencephalopathy (PML) in people using the Biogen Idec drug Tysabri (natalizumab) to treat multiple sclerosis (MS) or Crohn's disease (CD). The Stratify JCV Antibody ELISA test, when used with other clinical data from the patient, can help health care providers determine the risk for developing PML in MS and CD patients.
The John Cunningham virus (JCV) is a common virus that many people have been exposed to at some point in their lives, and is generally harmless. However, people with weakened immune systems, such as patients using immunomodulatory therapies like Tysabri, have an increased chance of developing PML from JCV. PML usually causes death or severe disability.
Currently, there is no treatment, prevention, or cure for PML, and no certain way to predict who will develop it. This test in conjunction with other factors will allow the physicians and patients to carefully assess the risks and benefits of continuing Tysabri treatment depending on the complete clinical information for the particular patient.
Tysabri is co-marketed by Cambridge, Mass.-based Biogen Idec and Elan Pharmaceuticals whose US operations are based in South San Francisco. (Source: FDA Website, 20 January, 2012)
The FDA has approved Pfizer's Inlyta (axitinib) to treat patients with advanced kidney cancer (renal cell carcinoma) who have not responded to another drug for this type of cancer. Renal cell carcinoma is a type of kidney cancer that starts in the lining of very small tubes in the kidney. Inlyta works by blocking certain proteins called kinases that play a role in tumor growth and cancer progression. Inlyta is a pill that patients take twice a day. Recently approved drugs for the treatment of kidney cancer include sorafenib (2005), sunitinib (2006), temsirolimus (2007), everolimus (2009), bevacizumab (2009) and pazopanib (2009). (Source: FDA Website, 27 January, 2012)
Genentech's Erivedge (vismodegib) has been approved by the FDA to treat adult patients with basal cell carcinoma, the most common type of skin cancer. The drug is intended for use in patients with locally advanced basal cell cancer who are not candidates for surgery or radiation and for patients whose cancer has spread to other parts of the body.
Erivedge, reviewed under the agency's priority review program, is the first FDA-approved drug for metastatic basal cell carcinoma. Erivedge was reviewed under the FDA's priority review program that provides for an expedited six-month review of drugs that may offer major advances in treatment. Basal cell carcinoma is generally a slow growing and painless form of skin cancer that starts in the top layer of the skin (epidermis). The cancer develops on areas of skin that are regularly exposed to sunlight or other ultraviolet radiation.
Erivedge is a pill taken once a day and works by inhibiting the Hedgehog pathway, a pathway that is active in most basal cell cancers and only a few normal tissues, such as hair follicles. Erivedge is being approved with a boxed warning alerting patients and health care professionals of the potential risk of death or severe birth effects to a fetus. (Source: FDA Website, 30 January, 2012)
The FDA recently 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, 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.
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 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. (Source: FDA Website, 31 January, 2012)
The FDA has granted the Novartis drug Gleevec (imatinib) regular approval for use in adult patients following surgical removal of CD117-positive gastrointestinal stromal tumors (GIST). GIST is a rare form of cancer that originates in cells found in the wall of the GI tract. These cells, known as interstitial cells of Cajal, are part of the autonomic nervous system, which regulates body processes such as food digestion. More than half of GISTs start in the stomach.
Gleevec is a pill that should be taken with a meal and a glass of water and was first approved by FDA in May 2001 to treat patients with advanced Philadelphia chromosome positive chronic myeloid leukemia, a blood and bone marrow disease linked to a genetic abnormality. (Source: FDA Website, 31 January, 2012)
The FDA has issued three draft guidance documents on biosimilar product development to assist industry in developing such products in the United States.
The Patient Protection and Affordable Care Act, signed into law by President Obama on March 23, 2010, amended the Public Health Service Act to create an abbreviated approval pathway - under section 351(k) - for biological products that are demonstrated to be highly similar (ie. biosimilar) to or interchangeable with an FDA-licensed biological product.
A biosimilar is a biological product that is highly similar to an already approved biological product, notwithstanding minor differences in clinically inactive components, and for which there are no clinically meaningful differences between the biosimilar and the approved biological product in terms of the safety, purity, and potency.
FDA will seek public comment on the guidance documents and instructions on how to submit comments will be announced in an upcoming Federal Register notice. In finalizing the guidance documents, the agency will consider the information received from the public. (Source: FDA Website, 09 February, 2012)
Bristol-Myers Squibb and AstraZeneca have announced that the FDA has issued a "complete response letter" regarding the New Drug Application (NDA) for investigational compound dapagliflozin for the treatment of type 2 diabetes in adults. The complete response letter requests additional clinical data to allow a better assessment of the benefit-risk profile for dapagliflozin. This includes clinical trial data from ongoing studies and may require information from new clinical trials.
The companies will work closely with the FDA to determine the appropriate next steps for the dapagliflozin application, are in ongoing discussions with health authorities in Europe and other countries as part of the application procedures, and remain committed to the drug and its development.
Bristol-Myers Squibb and AstraZeneca entered into a collaboration in January 2007 to enable the companies to research, develop and commercialize select investigational drugs for type 2 diabetes. Dapagliflozin, an inhibitor of SGLT2, a target in the kidney, is being investigated to evaluate its safety and efficacy in improving glycemic control in adults with type 2 diabetes, both as a monotherapy and in combination with other anti-diabetic agents.
The kidney plays an important role in glucose balance, normally filtering about 180g of glucose each day, with virtually all glucose being reabsorbed back into circulation. SGLT2 is a major sodium-glucose cotransporter in the kidney and is an insulin-independent pathway for the reabsorption of glucose back into the blood.
The Centers for Disease Control and Prevention estimate that approximately one in every 11 adults in the United States has diagnosed diabetes. Type 2 diabetes accounts for approximately 90 to 95 percent of all cases of diagnosed diabetes in adults. It is a chronic, progressive disease characterized by insulin resistance and dysfunction of beta cells in the pancreas, which decreases insulin sensitivity and secretion, leading to elevated glucose levels. Over time, this sustained hyperglycemia contributes to worsening insulin resistance and further beta cell dysfunction. To date, treatments for type 2 diabetes have focused primarily on insulin-dependent mechanisms. An approach that acts independently of insulin could provide an additional option for adults with type 2 diabetes.
Significant unmet need still exists as nearly half of treated patients remain inadequately controlled on their current glucose-lowering regimen. Many patients with type 2 diabetes have additional comorbidities (such as obesity) which may complicate glycemic control. (Source: BMS Website, 19 January, 2012)
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