Monthly Archives: March 2015

March 27, 2015 | By Márcio Barra

Kalydeco, a new orphan drug priced at over US$300,000 per year

A new study released today by the WHO Regional Office for Europe provides an in depth look at the challenges faced by European Member States health systems by the introduction of new, costly therapeutic entities, and the troubling economic burden they bring to the Member States.

As an array of new drugs reach Europe, healthcare expenditure with new drugs is increasing at an accelerated pace. Some of new, costlier drugs include Gilead’s Hepatitis C drug Sofosbuvir (Sovaldi), orphan drugs with prohibitive price tags, and new anti-cancer agents costing $6,000-10,000 a month.

The report’s main takeaway message is that European governments need to cooperate and encourage collaboration between payers on standards and criteria for evaluation of benefits and cost–efficiency of new medicines, seeing as some member states do not have mechanisms in place to evaluate cost-effectiveness. Governments should also promote transparency on price deals between countries with price regulatory agencies (such as the UK’s NICE) and countries with less developed health technology assessment methodologies.

The study highlights the fact that medicines should be priced according to the added therapeutic value that they bring to patients, and pricing systems should distinguish and reward meaningful clinical innovation. However, most countries, including Portugal, still rely on external reference pricing methods. This pricing system has a host of limitations including arbitration of the targeting price, launch delays (as countries with more expensive prices tend to have new drugs available earlier)  and the lack of incentive for innovation. Only Germany, Sweden and the United Kingdom do not use external referencing pricing, but instead free pricing mechanisms for pharmaceuticals.

While external referencing pricing remains the most popular option, more and more member states are starting to adopt health technology assessment to guide their reimbursement decisions, following the steps of  UK’s NICE, which is responsible for conducting and reviewing cost effectiveness analysis for new drugs, relying particularly on the quality‐adjusted life-year (QALY).

You can read the full report here

March 24, 2015 | By Márcio Barra


Last week, a warning letter was issued by Gilead to doctors informing that the combination of Gilead’s innovative hepatitis C drugs Harvoni (sofosbuvir/ledipasvir) or Sovaldi (sofosbuvir) with amiodarone (an antiarrhythmic drug generally reserved for difficult cases ) may cause potentially fatal heart arrhythmias.

The news comes after an FDA label update of the drugs, following a series of reports from Gilead describing symptomatic bradycardia events in nine patients who took the medications along with amiodarone. Seven of the nine patients were also taking a beta-blocker. One patient died from cardiac arrest after treatment and three others received a pacemaker.

The FDA label update provides further information on the bradycardia events, detailing that they generally occurred within hours to days, but there were cases where the events happened up to 2 weeks after initiating Hepatitis C treatment. The effect mechanism of this interaction is still unknown. The label update informs that, for patients who have to be prescribed with amiodarone, they should undergo cardiac monitoring for 48 hours after first administration and then daily heart-rate monitoring either done in the outpatient or in a home setting for 2 weeks. The same monitoring rules should be followed for those who discontinue amiodarone, due to the drug´s long half-life.

While the combination can be potentially fatal, Wall Street analysts are reporting that the news will have”zero impact” on sales.  This is due to the fact that there are a relatively small number of hepatitis C patients taking Gilead’s new drugs alongside amiodarone. Regional prescribing practices could also be a factor here, seeing as most of the cases of seriously slow heart rates occurred in France, where amiodarone is more widely prescribed.



WSJ Pharmalot

March 19, 2015 | By Márcio Barra


The Bial group announced today that the BIAPARK I phase III clinical trial study evaluating Opicapone, an investigational peripheral COMT inhibitor for people with Parkinson´s Disease, obtained positive results. This is the second new investigational drug developed by Bial, following Zebinix (eslicarbazepine acetate).

Opicapone is a selective and reversible COMT inhibitor, to be used in combination with L-DOPA/ Carbidopa or L-DOPA/benserezide. The drug increases L-DOPA plasma levels when administered alongside L-DOPA, through inhibition of the O-methylation of L-DOPA by the COMT enzyme, thus increasing L-DOPA´s plasma half-life. In the BIAPARK I study, the drug was compared to Entacapone, another COMT inhibitor, and placebo. The study results, which will be presented today at the 12th International Conference on Alzheimer’s and Parkinson’s Diseases and Related Neurological Disorders in France, show that the daily intake of 50 mg of Opicapone led to a significant reduction (2 hours) of the OFF-time period compared to placebo. Moreover, Opicapone was considered overall safe and well tolerated.

Currently, there are two COMT inhibitors available on the market, Tolcapone and Entacapone. Of the two, Tolcapone is the more efficacious, reducing OFF time in 98 minutes when compared to placebo, versus 41 minutes for Entacapone. Tolcapone´s use however, is hindered by its potential hepatic toxicity. Both drugs also require multiple dosages over the day, while Opicapone is once-daily.

Professor Joaquim Ferreira, ‎Professor of Neurology and Clinical Pharmacology at the University of Lisbon, said, “In the last 10 years, there have been few new treatment options in Parkinson’s disease. Opicapone intends to fulfil the need for a more potent COMT inhibitor.”

Professor Andrew Lees, Professor of Neurology at the National Hospital for Neurology and Neurosurgery, London, added, “Opicapone offers an important alternative to the currently available COMT inhibitors, with convenient once-daily dosing.”

The BIPARK I clinical trial recruited a total of 600 patients over 106 study centers spread over Europe, including Portugal.



A systematic review of catechol-0-methyltransferase inhibitors: efficacy and safety in clinical practice.


March 16, 2015 | By Márcio Barra

Luis Portela, the non-executive chairman of Bial Laboratories (a Portuguese  pharmaceutical company responsible for the development and commercialization of Zebinix) in an interview at Rádio Renascença, said that drug prices in Portugal are, on average, among the lowest in Europe, mirroring the prices practiced in Slovenia and Estonia.

“The average price of drugs in Portugal is around 10.09 euros. Of course there are drugs that are more expensive, but Portugal has prices at the same level as those from Slovakia and Estonia. Portugal´s prices are among the cheapest prices in Europe and on average fell 30% in the last three to four years, “said Luis Portela.

When discussing the recent price reduction of Gilead´s controversial hepatitis C drug Sovaldi (sofosbuvir) in Portugal, Luis Portela stated that  increasing price cuts hurt innovation, especially when taking into account that there are only 25 institutions in Europe creating new medicines.

This statement echo previous comments by Luis Portela regarding the effect of drug price cuts in Portugal and how they are hurting pharmaceutical companies, including Bial. Luis Portela mentioned in 2013 that Bial had to postpone the development of a new Parkinson´s Disease drug due to budget constraints.  

Portugal drug prices are revised yearly. This year pricing revision will be made by referencing the values practiced in Slovenia, Spain and France.



Rádio Renascença

March 11, 2015 | By Márcio Barra



(Note: all references used are in the comments)

The modern clinical trial is a significant undertaking, and one that requires a multidisciplinary team(1). The current research team includes the principal investigator, sub – investigators, data managers, statisticians, clinical research coordinators (CRC), and the monitor or clinical research associate (CRA).

The International Conference on Harmonization (ICH) E6 Good Clinical Practices guidelines defines monitoring as “The act of overseeing the progress of a clinical trial, and of ensuring that it is conducted, recorded, and reported in accordance with the protocol, Standard Operating Procedures (SOPs), Good Clinical Practice (GCP), and the applicable regulatory requirement(s)”. CRAs are responsible for monitoring the trial, a task which ensures the integrity of the data that is being collected. It also allows the sponsor to closely follow the study centres, evaluate their conduct, and identify bottlenecks in patient recruitment(3).

In the past, it was the sponsor that would send their personnel to research sites to carry out the monitoring activities. This changed in the early nineties, with the emergence of contract research organizations (CROs). Like many other aspects of trial conduction, monitoring began to be outsourced (4).

The ICH guidelines state that data should be accurate, complete, legible, and timely. However, they do not provide instructions on how to approach data monitoring or individualized approaches for different types of trials. This leaves room for the industry to experiment with different strategies for trial monitoring, and with the advent of EDC, news ways to monitor clinical trial data are becoming more and more common.

On-Site Monitoring

On-site monitoring is the current industry standard, and one that has stuck with clinical trials for some decades (6). Here, the CRA is assigned to monitor a clinical trial or an observational study in a study centre or group of study centres, and then carries an in-person site evaluation (6). The most significant activities carried out by a CRA include: (1) the study initiation visit, where the CRA visits the centre to prepare the study staff for conducting the study; (2) several monitoring visits to a centre during the course of the trial; and (3) the study closure visit.

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March 9, 2015 | By Márcio Barra

Last Friday, the FDA issued the first approval in the U.S. of a biosimilar – Zarxio, made by Sandoz, the generics division of Novartis. The drug is a biosimilar of Amgen´s chemotherapy recovery agent Neupogen (Filgastrim, for the treatment of neutropenia), originally released in 1991.

This approval comes as a hit to Amgen´s, seeing as the company´s portfolio largely of biologicals to support cancer patients. Last year sales of Neupogen amounted to $1.2 billion. Future pressure is also incoming, as Sandoz is currently pursuing FDA approval of two more biosimilars of Amgen drugs: Neulasta (pegfilgrastim), also for the treatment of neutropenia, and Enbrel (etarnecept), for the treatment of rheumatoid arthritis. Hospira, recently acquired by Pfizer, is also seeking approval of a biosimilar of Amgen´s Epogen (human erythropoietin), for the treatment of anemia.

Biosimilars serve a similar purpose as generic drugs, but with some key differences and more stringent requirements, owing to the differences in replicating large molecules compared to smaller molecules. Seeing as biologic drugs are produced from living organisms, the production processes are quite sensitive to changes in the manufacturing processes, and thus is it very hard to create an exact replica of the original molecule. Biosimilars must be shown that they have no clinically meaningful differences in regards to safety and effectiveness from the reference product.

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