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Portugal

By Marcio Barra

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More than 30 new drugs, some with novel mechanisms of action which are already used in other European countries, are currently waiting for authorization by the Portuguese National Competent Authority, some for more than a year. The president of the board of APIFARMA, João Almeida Lopes, in a newspiece on the SIC tv channel commented that he believes these delays are due to economic reasons.

Some of the delays extend over a year, whereas current law sets a 75 day time limit for approval.

Below is a list of the drugs currently waiting for commercialization approval in Portugal:

 

Brand name Molecule Indication Marketing Authorization holder Reported reason for delay
Zydelig Idelalisib Zydelig is a cancer medicine that is used to treat chronic lymphocytic leukaemia (a cancer of a type of white blood cells called B lymphocytes) used in combination with another medicine (rituximab) Gilead The first contract proposal was presented by INFARMED in September 2015
Affinitor Everolimus Affinitor is a cancer treatment for advanced breast cancer in women who have been through their menopause. Novartis Contract was received. Process not yet concluded
Votubia Everolimus Used to treat benign tumours caused by the genetic disease tuberous sclerosis Novartis Economic study not yet started
Cosentyx Secukinumab Moderate to severe plaque psoriasis Novartis Parity with the comparator
Cosentyx Secukinumab Ankylosing spondylitis when conventional treatments do not work well enough. Novartis Economic evaluation not yet started
Xolair Omalizumab Chronic urticaria Novartis  –
OFEV Nintedanib Idiopathic pulmonary fibrosis (IPF) Boehringer-ingelheim Orphan indication
Vargatef Nintedanib Cancer medicine used to treat adults with non-small cell lung cancer. Boehringer-ingelheim  –
Praxbind Idarucizumab Reversal agent for Pradaxa Boehringer-ingelheim  –
Giotrif Afatinib Non-small cell lung cancer boehringer-ingelheim  –
Xofigo Radium-223 dichloride Treatment of adults with castration-resistant prostate cancer, symptomatic bone metastases and no known visceral metastases Algeta and Bayer Waiting for a cost minimization analysis from INFARMED. Waiting opinion from the Comissão Nacional de Farmácia e Terapêutica
Stivarga Bayer Gastrointestinal stromal tumor  Bayer Currently under economic evaluation and Waiting the opinion of the Comissão Nacional de Farmácia e Terapêutica
Stivarga  Bayer Colorectal cancer  Bayer Reportedly looking for solutions to assure accessibility to patients. Waiting opinion from the Comissão Nacional de Farmácia e Terapêutica
Zytiga Abiraterone acetate Treatment of prostate cancer  Janssen Accelerated approval by the EMA.

Recognition of added therapeutic value.

Imbruvica Ibrutinib Chronic lymphocytic leukaemia  Janssen Breakthrough therapy designation by the FDA. Recognition of added therapeutic value.
Imbruvica Ibrutinib Mantle cell lymphoma  Janssen Breakthrough therapy designation by the FDA. Recognition of added therapeutic value.
Olysio  Simeprevir  Chronic hepatitis C   Janssen Recognition of added therapeutic value. An estimated 300 patients missing Harvoni (sofosbuvir)
Velcade Bortezomib Patients with non-previously treated multiple myeloma  Janssen
Velcade Bortezomib Previously untreated patients who are going to receive high-dose chemotherapy followed by a blood stem-cell transplant. In this group of patients, Velcade is used in combination with dexamethasone, or with dexamethasone plus thalidomide;  Janssen Therapeutic standard in all guidelines. Recognition of added therapeutic value.
Sylvant Siltuximab Treatment of multicentric Castleman’s disease in adults who tested negative for the human immunodeficiency virus (HIV) and the human herpesvirus-8 (HHV-8)  Janssen Orphan disease –roughly 9 patients each year. Recognition of added therapeutic value
Sirturo Bedaquiline Sirturo is used in combination with other tuberculosis medicines in adults with tuberculosis that is affecting the lung and that is multi-drug resistant (resistant to at least isoniazid and rifampicin, two standard tuberculosis medicines).  Janssen New molecule for tuberculosis. Orphan disease –roughly 3 patients each year. Recognition of added therapeutic value
lynparza Olaparib First oral treatment for women with BRCA-mutated advanced ovarian cancer who have received 3 or more prior chemotherapy medicines  AstraZeneca Oprhan drug. Currently undergoing economic evaluation. Waiting opinion from the Comissão Nacional de Farmácia e Terapêutica
Toujeo Insulin glargine injection Used to treat diabetes in adult patients  Sanofi-Aventis New formulation. Waiting decision on charges limit.
Keytruda Pembrolizumab used to treat adults with melanoma that has spread to other parts of the body or cannot be surgically removed.  Merck Formal negotiations with INFARMED have begun, and a final proposal has been reached.
Zontivity Vorapaxar Used to reduce the occurrence of atherothrombotic events such as further heart attacks or strokes in adult patients who have already had a heart attack. It is given in combination with aspirin and clopidogrel.  Merck Under pharmacoeconomic evaluation
Isentress Raltegravir Isentress is indicated in combination with other anti-retroviral medicinal products for the treatment of human immunodeficiency virus (HIV-1) infection in adults, adolescents, children,toddlers and infants from the age of 4 weeks  Merck Under pharmacoeconom ic evaluation
Genoya Elvitegravir/Cobicista/Emtricitabine/Tenofovir alafenamide HIV-1 Gilead
Zerbaxa Ceftolozane and tazobactam. Antibiotic used to treat adults with complicated (difficult to treat) bacterial infections affecting:

·        tissues and organs within the belly (intra-abdominal infections);

·         the kidneys (pyelonephritis);

·         the urinary tract (structures that carry urine, such as the bladder).

 Merck Waiting opinion from the Comissão Nacional de Farmácia e Terapêutica
Adempas Riociguat It is used to increase the ability to carry out physical activity in adults with Chronic thromboembolic pulmonary hypertension and Pulmonary arterial hypertension  Bayer
Jardiance  Empagliflozin  Type 2 diabetes Boehringer Ingelheim
Pradaxa´s third indication Dabigatran etexilate Treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE), and prevention of recurrent
DVT and PE in adults
Boehringer Ingelheim
Eylea  Aflibercept Diabetic macular edema  Bayer Currently in contract negotiation. Waiting opinion from the Comissão Nacional de Farmácia e Terapêutica
Eylea  Aflibercept Occlusion of the central retinal vein  Bayer Currently in contract negotiation.
Stelara  Ustekinumab  Janssen New indication. Equivalent added therapeutic value
Rezolsta Darunavir / cobicistat Human immunodeficiency virus type 1 (HIV-1)  Janssen New fixed association. Equivalent added therapeutic value
Triumeq Abacavir, dolutegravir and lamivudine Human immunodeficiency virus type 1 (HIV-1)  ViiV Healthcare New fixed association. Equivalent added therapeutic value

By Márcio Barra

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Six people were hospitalized in the Hospital of Rennes, France in serious condition, and one is brain dead, following a Phase I first-in-man clinical trial with a new drug  from the Portuguese pharmaceutical company BIAL.  The clinical trial was being conducted by French company Biotrial.

The French Health Minister, Marisol Touraine said on Friday that it is a “serious accident”. The minister added that the accident happened on Thursday and that the trial was suspended, with all previous volunteers called to undergo tests.

There are several reports online describing the drug as an analgesic product based on cannabis, but little to new additional details are being reported. Looking at BIAL´s R&D pipeline, the agent appears to be BIAL´s BIA 10-2474. BIA 10-2474 is described as a new small molecule drug that acts on the Central Nervous System as a painkiller, and currently undergoing Phase I trials.

pipeline_EN_09112015

Reports state that a total of 8 participants were participating in the trial, with two taking placebo. A message on Biotrial´s website reads:

During a FIM study which was being conducted for a sponsor, serious adverse events related to the test drug  have occurred in some subjects at our CPU. The trial has been conducted in full compliance with the international regulations and Biotrial’s procedures were followed at every stage throughout the trial, in particular the emergency procedures for the transfer of subjects to the hospital. We are in close and regular contact with the Health Authorities and Ministry in France. The priority at Biotrial remains the safety of our subjects. We are very grateful for the support we have been receiving from our clients and partners today.

BIAL is still verifying the occurrence, since the drug has been used successfully in other subjects with no issues.

By Márcio Barra

FILE - This undated file photo provided by Gilead Sciences shows the hepatitis C medication Sovaldi. Gilead Sciences says it has reached a deal with several generic drugmakers to produce cheaper versions of its popular, expensive hepatitis C drug Sovaldi for use in developing countries. (AP Photo/Courtesy of Gilead Sciences, File)

Sofosbuvir, Gilead´s Hepatitis C drug which is making waves due to its high cure rate (approximately 90%) and high treatment cost, has already cured 651 Hepatitis C patients in Portugal since it was made available, according to the National Competent Authority INFARMED to Diário de Notícias.

The drug (marketed as Sovaldi for the Sofosbuvir-only formulation, and as Harvoni for the combination of Ledipasvir and Sofosbuvir) was made available following an agreement between the Ministry of Health, INFARMED and Gilead Sciences to treat 13,000 hepatitis C patients. The agreement was concluded on February 2015 following weeks of negotiations. So far, 5322 patients are currently undergoing treatment, with 683 reaching the end of treatment. 32 patients were not cured of Hepatitis C, and hospitals have not reported the causes for the non-response to treatment. As for the total cost of payment per patient, the amount remains undisclosed.

In Portugal, it is estimated about 100,000 people are living with hepatitis C and a large proportion of them have developed cirrhosis. The prices of Sofosbuvir across European member states- in excess of €50,000- make Sobusfuvir a heated topic of discussion among healthcare regulators.

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 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.

Sources:

Bial 

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.

 

Source:

Rádio Renascença

February 10, 2015 | By Márcio Barra

INFARMED published in its news bulletin a study providing an overview of the consumption trends of anticoagulant therapy in Portugal, from 2010 to 2013.  1 The report shares some interesting numbers, especially when considering the new molecules that have been released during the timeframe, namely the new oral anticoagulants (NOACs). The full version is supposedly available in the regulators website, but unfortunately I was unable to find it.

In the last 5 years, the NOACS, of which there are the direct inhibitors of factors IIa (Dabigatran, commercial name Pradaxa) or factor Xa (Rivaroxaban, commercial name Xarelto, and Apixaban, commercial name Eliquis), have been granted European and US marketing authorization for the prevention of thrombotic events, such as stroke and systemic embolism, in high-risk adult patients. A third factor Xa inhibitor, Edoxaban (commercial name Savaysa) was recently approved in the USA by the FDA for the prevention of stroke and embolic events in patients with non-valvular atrial fibrillation. These drugs overcome some limitations associated with the traditional oral and parenteral anticoagulants, such as Warfarin and Low Molecular Weight Heparins, such as frequent monitoring of INR. As for efficacy, NOACs’ efficacy across a whole spectrum of prothrombotic conditions is, at least, non-inferior to the standard care. 2

Concerning safety, as any other new drug in the market, there are still unknowns associated with these drugs, alongside the fact that, unlike established agents such as Warfarin, at the moment there is no antidote available to reverse the anticoagulant effect. (Boehringer Ingelheim has an antidote currently in clinical development, idarucizumab. Initial Phase I study results appear promising. 3

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