Latest approvals by the US FDA
• The proton pump inhibitor (PPI) Nexium (esomeprazole magnesium) is indicated for short-term treatment of gastroesophageal reflux disease (GERD) in children ages 1 to 11 years old. Nexium is manufactured by AstraZeneca [1].
• Xyntha Antihemophilic Factor (Recombinant) Plasma/Albumin Free is a new treatment for hemophilia A. Hemophilia A is a hereditary blood-clotting disorder that affects mainly males. It is caused by a mutation of the factor VIII, resulting in clotting factor VIII deficiency. Xanthia is a genetically engineered version of factor VIII. It is manufactured by Wyeth Pharmaceuticals Inc. [2].
• The Interleukin-1 blocker Arcalyst (rilonacept) is an orphan drug indicated for the treatment of two Cryopyrin-Associated Periodic Syndromes (CAPS) disorders. CAPS are very rare conditions of inflammation. Orphan drugs are drugs intended for the treatment of rare diseases. To make it worthwhile for drug companies to develop such drugs in the US, manufacturers of orphan drugs enjoy tax incentives and longer period of exclusivity as provided for by the US Orphan Drug Act. Arcalyst is manufactured by Regeneron Pharmaceuticals Inc. [3].
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Recalls and OTC Disapproval: A Gloomy December for Merck
This is definitely not Merck’s month.
On 12 December 2007, Merck announced the voluntary recall of potentially contaminated batches of the influenza vaccines PEDVAXHIB and COMVAX. These vaccines are indicated for infants and young children for protection against the seasonal flu and hepatitis B. The affected batches were distributed in April 2007 [1].
On another front, a US FDA advisory panel voted against Merck’s application for the prescription drug Mevacor 20 mg to be sold over-the-counter. Mevacor (lovastatin) is indicated for the treatment of elevated cholesterol levels. It has been on the market as a prescription drug since 1997. The panel’s recommendation is based on concerns of the use of the drug by misinformed consumers who may not actually benefit from it. The recommendation is not binding and a final decision would be reached in January 2008 [2].
Merck News Item, 12 Dec 2007
Merck News Item, 13 Dec 2007
Nexavar Approved for Liver Cancer Treatment
The US FDA has recently approved the oral kinase inhibitor Nexavar (sorafenib) for use in patients with hepatocellular carcinoma, an inoperable form of liver cancer. This makes Nexavar the “first FDA-approved drug therapy for liver cancer.” Nexavar was originally approved in 2005 for treatment of advanced kidney cancer and is currently marketed in over 60 countries for this indication [1, 2].
The FDA approval came about month after Nexavar was centrally approved in Europe in October for the new indication. The appproval was based on results of a randomized placebo-controlled trial involving 602 patients with hepatocellular carcinoma. The study results showed an average extended survival of 2.8 months in patients treated with Nevaxar compared to placebo. Tumor progression was also observed to be slower.
“Nexavar, an oral anti-cancer drug, is the first approved systemic drug therapy for liver cancer and the only drug therapy shown to significantly improve overall survival in patients with the disease.” [1,2]
Nexavar is manufactured by Bayer Pharmaceuticals Corporation of Germany.
[2] Bayer Press Release, 19 Nov 2007
Avandia Remains on Market but with Additional Warning
The US FDA has recommended that Avandia (rosiglitazone) be allowed to remain on market. However, additional warning has been inserted in the existing boxed warning in the product’s labeling. The new warning highlights the potential increased risk for cardiovascular events, especially myocardial infarction [1].
Avandia, manufactured by GlaxoSmithKline (GSK), was approved for marketing in 1999 in the US as oral treatment for type-2 diabetes mellitus. It has the advantage that it can be used as a stand-alone therapy or as co-therapy with other oral anti-diabetes treatments.
An article in NEJM early this year reported a meta-analysis of 42 randomized controlled clinical trials on rosaglitazone. The results show that “rosiglitazone was associated with a significant increase in the risk of myocardial infarction and with an increase in the risk of death from cardiovascular causes that had borderline significance.” [2]
The FDA has requested GSK to conduct a new long-term postmarketing study to evaluate the potential cardiovascular risk of Avandia and the manufacturer agreed to comply [1]. The study is expected to be concluded by 2014.
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Limits on MRI Use in the EU postponed
The EU decided to postpone introducing a law regulating workers’ exposure to electromagnetic fields [1]. The decision is based on the fact that such as legislation would place serious limits on the use of magnetic resonance imaging (MRIs).
Directive 2004/40/EC was aimed to protect workers against the occupational hazard of electromagnetic field exposure and was to take effect in April 2008 [2]. However, the high occupational limit values set by the directive would inadvertently put a ban on the use of MRI in diagnostic medicine.
“MRI is currently the leading technique for detecting brain tumours and many other serious conditions. It allows doctors to help 8 million patients each year…[the EC] is well aware of the enormous benefits of MRI and of its immense value for public health.” [1]
Other international agencies such as the International Commission on Non-Ionising Radiation Protection (ICNIRP) and the World Health Organisation (WHO) are looking into revising the current occupational limit values for electromagnetic fields [1]. The EU will probably introduce a revised directive based on similar limits in 2012.
In the meantime, the EU is pushing for more research in this field. It is funding projects under the 7th Framework Programme for Research to explore hybrid imaging systems such as MRI/PET and MRI/Ultrasound [1].
Sources:
[1] EU Press Release 26/10/2007. Commission to postpone and amend electromagnetic fields legislation to protect MRI Reference: IP/07/1610.
[2] Directive 2004/40/EC of the European Parliament and of the Council of 29 April 2004. Official Journal of the European Union L 159.
Viracept back in the European market
The protease inhibitor Viracept (nelfinavir) is available again in Europe. On 19 Oct 2007, European regulatory authorities reinstated this anti-HIV drug’s market authorisation in the EU [1].
Nelfinavir was first introduced in 1999 and Roche is responsible for supplying the drug in Europe. Last summer, several batches of Viracept were found to have higher-than-normal ethyl mesylate sulphonate (EMS) content. EMS is a known mutagen and teratogen.
There was a wide-spread recall of the product and it was taken off the European market upon the recommendation of European Medicines Agency (EMEA) [2].
Roche immediately took the appropriate steps to correct the manufacturing problems which apparently satisfied the European regulatory authorities, leading to its reinstatement.
Bad News and Good New for Novartis
Within a period of 2 days, Novartis has suffered a loss in the US and scored a victory in Europe.
On 27 Sept 2007, the USFDA disapproved the COX-2 inhibitor Prexige (lumiracoxib). The drug is indicated for the treatment of osteoarthritis. Although marketed in many countries, the FDA is not fully convinced of the drug’s benefit-risk balance even after submission of additional safety data [1].
On the positive side, Galvus (vildagliptin) was granted marketing approval in the EU on 28 Sept 2007. Glavus is an oral DPP-4 inhibitor indicated for Type 2 diabetes. The centralised procedure marketing license is valid in 27 EU countries and the two EFTA countries Norway and Iceland.
It is not smooth sailing for Galvus in the US, either. Its approval in the US is delayed this year due to safety issues concerning patients with renal impairment. New clinical trials are ongoing to resolve these issues.[2].
[1] Novartis Media Release, 27 Sept 07. Prexige® receives ‘’not approvable'’ letter in the US despite being one of the most studied COX-2 inhibitors.
[2] Novartis Media Release, 28 Sept 07. Galvus® receives European approval as new treatment for type 2 diabetes with broad range of indications.
Things are looking up for generics: the recent approvals and victories
Generic drug manufacturers scored another victory this week. On 5 Sept 2007, the US FDA announced the approval of the first generic versions of GlaxoSmithKline’s Coreg (carvedilol). In total, 14 drug companies were given the go signal to market their Coreg-like generics indicated for the treatment hypertension, heart failure, and left ventricular dysfunction following myocardial infarction.
Last month, the FDA approved the Israeli drug company Teva’s application to market a generic form of Famvir (famciclovir), an antiviral drug used to treat genital herpes. Famvir is a patented product of the pharmaceutical giant Novartis.
Last week, a Swiss court approved the application of the generic manufacturer Mepha to continue the marketing of the generic version of Fosamax (alendronate), a drug indicated for the treatment of osteoporosis developed by Merck, Sharp & Dohme.
Although patent litigations are still ongoing between the major players in the field, the generics companies are already making headways in the pharmaceutical industry. These recent developments will benefit grateful consumers but put the big pharmaceutical companies at a disadvantage.
New Drug Application in Europe
Do you think that getting approval for a new drug in the US is a real pain? Try your luck in Europe. One may wonder how it can be so different on the two sides of the Atlantic after the guidelines for Common Technical Document (CTD) were set in place. Well, we shouldn’t forget that the US is a single country while Europe is a whole continent. Below is a very brief overview of the procedures a new drug applicant has t
o go through to break into the European market.
The European Medicines Agency (EMEA) is the EU counterpart of the US FDA as the main regulatory institution. In addition, each member state has its own regulatory board. We are talking here about 27 member states and 3 EFTA countries, making it 30 countries in total. There are three procedures to get a drug approved in Europe and there are strict guidelines as to which products should follow which procedure.
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The Centralised Procedure is obligatory for products which include among others, drugs against HIV and cancer and products derived by recombinant DNA and monoclonal antibody technologies. In 2008, some more products will be obliged to follow this procedure. The end result of this procedure is a single marketing authorisation and a single trade name for all 30 countries.
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The Decentralised Procedure (DCP) is for products not qualified for the centralised procedure and have not received a marketing authorisation in any of the EU/EFTA countries. It involves parallel submissions to the member states chosen by the applicant. The end results are several marketing authorisations and different trade names.
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The Mutual Recognition Procedure (MRP) is for products which have already been granted a marketing authorisation from an EU/EFTA country. If the applicant wants to expand this authorisation to other countries, then this is the way to go. The end results are similar to those of the DCP.
Take note that for both DCP and MRP, the submission dossier should be translated into the official languages of the countries in question.But don’t worry. Complicated as they may be, all submission procedures actually follow well-defined steps and strict timelines. And - they work!!!