Incredible journeys: Robert Donnell plots the course of a new medicine

by Robert Donnell 17. January 2017 10:51


While plotting their way to our medicine cabinets new drugs won’t always use the most obvious map


The path of a new drug – from research to licensing – is a familiar one to companies seeking to take their products to market. There are still, however, potential stalling points, before the treatment reaches the patient.

Even when the data on the drug’s Phase I – III trials has been announced, and published, in peer-reviewed journals, there is still the hurdle of gaining licensing from the appropriate regulatory authority. And even when it has been licensed, it may not be available in certain countries, due to an absence of sales infrastructure, or because it is not commercially viable to launch.

Take Europe, for instance. The European Medicines Agency will grant marketing authorisation for a drug in 28 countries, but a pharma company may not launch in all those separate countries simultaneously. Certain larger markets – including the UK, Germany and France – take precedence. Due to internal capacity, commercial return or reimbursement issues, there may be a delay of months – or even years – before the product is launched in all countries.

In circumstances where a drug has not yet been commercialised and made available through the normal supply chain, Managed Access Programmes (MAPs) can provide a valuable way of helping a patient with unmet medical needs. Indeed, MAPs represent a realistic, boundary-resilient way of providing patients or physicians – who know a drug exists somewhere else in the world – with a realistic opportunity of accessing the treatment.

MAP is a collective name for the different regulatory compliant programmes that countries have devised to help the patient with an unmet clinical need. These programmes vary in name, and some people may be more familiar with other terms, such as Named Patient Programmes, Early Access and Compassionate Use Programmes.

With the appropriate MAP, an unregistered drug can be supplied to a patient with a physician-assessed unmet clinical need, before the drug is available in the respective country.

Although this process and concept is counter-intuitive to many people in the industry, MAPs are becoming more common. The timing of a MAP may vary, and the therapy could surface when the drug is licensed in other countries, but not the patient’s country. Furthermore, it could materialise when the drug is licensed in the patient’s country – but unavailable due to the pharma company not having launched it there – or before the drug has been licensed anywhere.

As you would imagine, MAPs are not easy to execute, requiring highly-specialised regulatory customer service and operational expertise in order to deal with distribution issues that exist outside the usual industry processes. Factors such as patient criteria, regulations and importation protocols – all of which vary from country to country – need to be taken into account.

For the pharmaceutical industry, MAPs can be understandably unfamiliar terrain, but this is where their role in facilitating patient access to drugs comes into sharp focus.


In sickness and in stealth

Patients are following MAPs in increasing numbers

Ultimately – whatever the stage – a regulatory compliant programme is required to get the drug to the patient who needs it, outside of the usual regulatory and supply chain framework that the pharma industry operates within.

Counter-intuitive, yes, but also crucial. Without the MAP, the patient would have to wait months or years to gain access to a drug that could ease their suffering or even save their life.

MAPs are also used to help deal with orphan diseases – conditions that affect fewer than 200,000 people nationwide. There are between 6000-8000 orphan diseases, many of which affect only a few hundred patients.

On these occasions, it is not feasible for a pharmaceutical company to set up supply chains across all regions in which patients are suffering from a particular orphan disease, or even have the drugs registered in each of those countries. Here again, a MAP can provide treatment options that would otherwise be out of reach.

With such an array of uses, then, it is unsurprising that MAPs – despite being so different to the rest of the industry – are not uncommon. They can be found across the world, whether it’s the Temporary Authorisations for Use programme in France, the European-wide compassionate use programme, or with different countries’ individual patient programmes.

And although some in the industry approach the world of MAPs with uncertainty – and others are still unaware of their existence – awareness is increasing rapidly. This is not just limited to within the industry either – these days, patients around the world with the same diseases can connect and share information online.


Robert Donnell is Head of Business Development at Durbin. Go to


Editor’s view

Access to medicine is an emotive subject, which brings with it a complex moral and regulatory maze – it’s exceptionally difficult to navigate for both patient and healthcare professional. One only has to reflect on the Cancer Drug Fund narrative to emphasise how carefully these processes have to be handled.

The truth that dare not speak its name is that desperate patients don’t care whether something has been approved, or whether all the boxes have been ticked. If they’ve only got six months to live – they’ll take anything.

Without access to real or perceived life-saving treatments, patients can very easily be tempted into the unscrupulous recesses of alternative medicine or even attempt to source therapies on the black market.

This is well demonstrated by Ron Woodroof’s pursuit, during the 1980s, of HIV/AIDS drugs in the film, Dallas Buyers Club. After being denied therapies in his own country – even when they have been approved for another condition – Ron smuggles drugs from Mexico and bribes healthcare professionals (as you do).

This is extreme, but it serves to remind us that, in pursuit of life, humans will do almost anything. With this considered, legitimate alternatives must be encouraged.  



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Sanofi and Regeneron's marketing authorisation application for Dupixent® accepted for EMA review

by Amy Schofield 8. December 2016 11:57

The European Medicines Agency (EMA) has accepted for review the marketing authorisation application (MAA) for Sanofi and Regeneron Pharmaceuticals' Dupixent® (dupilumab) for the treatment of adults with moderate-to-severe atopic dermatitis (AD) who are candidates for systemic therapy.

The investigational biologic therapy inhibits signalling of IL-4 and IL-13, two key cytokines required for the type 2 (including Th2) immune response, which is believed to be a major driver in the pathogenesis of the disease.

The MAA for Dupixent contains data from three Phase 3 pivotal studies in the global LIBERTY AD program, that included more than 2500 patients. The objective of the studies was to evaluate Dupixent as monotherapy (SOLO 1 and SOLO 2) and in concomitant administration with topical corticosteroids (CHRONOS), in adult patients with moderate-to-severe AD whose disease is not adequately controlled with topical prescription therapies. 

A biologics license application for Dupixent was accepted for Priority Review by the U.S. Food and Drug Administration in September 2016. The EMA and FDA have conditionally accepted Dupixent as the trade name for dupilumab.

Dupixent is currently under clinical development and its safety and efficacy have not been fully evaluated by any regulatory authority. In addition to AD in adults, Dupixent is being studied in paediatric AD, asthma, nasal polyposis and eosinophilic oesophagitis. If approved, Dupixent would be commercialised by Regeneron and Sanofi Genzyme, the specialty care global business unit of Sanofi.

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Clinical trial transparency "steadily" improving

by Amy Schofield 24. November 2016 12:51

Pharmaceutical companies are showing a ‘significant trend’ towards increased clinical trial transparency, according to a new ABPI study.

The study shows results of 90% of clinical trials on all 34 new medicines approved by the European Medicines Agency (EMA) in 2013 were disclosed within a 12-month timeframe.

'Clinical trial transparency of recently approved medicines', is published in the peer-review journal Current Medical Research and Opinion (CMRO), and is the latest in a series spanning a five-year period.

Together with results from two earlier studies, this research, conducted by Livewire Editorial Communications on behalf of the ABPI, indicates that the disclosure rate of industry-sponsored clinical trials at 12 months has steadily improved year on year from 71% in 2009 to 90% in 2013.

This study assessed all completed company-sponsored trials related to new medicines approved by the EMA in 2013 and shows that of the 539 evaluable company-sponsored clinical trials related to 34 new medicines licenced to 24 different companies:


  • 484 (90%) had been disclosed on a registry or in scientific literature within 12 months of first regulatory approval or trial completion.
  • 500 (93%) had results disclosed by the end of the study at 31 July 2015.
  • Larger, phase III trials reached disclosure rates of 93% (210/225) within 12 months and 95% (214/225) at 31 July 2015.
Dr Jacintha Sivarajah, Head of Medical Affairs at the ABPI, said: “These latest findings highlight the trend towards increasing rates of disclosure for pharmaceutical industry-sponsored clinical trials, reaffirming the industry’s commitment to greater transparency across all of its relationships and activities."

72% (28/39) of the undisclosed trials were early phase I or II trials. Many of these were initiated more than 10 years ago, prior to the publication of industry commitments, implementation of regulatory requirements and the availability of clinical trial registries, and at a time when they would not have been expected to be published as individual studies.


Dr Bryan Deane, co-author of the report, said: “As long as medicines that began development before 2005 are still reaching approval the disclosure rate is unlikely to reach 100%. These early stage trials pre-date industry’s commitment to greater transparency. 

“However, now that registration and reporting of clinical trials has become routine and industry, particularly large multinational companies, is increasingly focussing on ensuring its transparency requirements are fulfilled, it is reasonable to expect that the trend for increased disclosure rates will continue.”


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General | News

PharmaMar seeks European marketing authorisation for multiple myeloma treatment

by Amy Schofield 23. September 2016 08:32

PharmaMar has announced the submission to the European Medicines Agency of the marketing authorisation application (MMA) for Aplidin® (plitidepsin) in combination with dexamethasone for the treatment of relapsed/refractory multiple myeloma.

The application follows positive data obtained from the randomised, Phase III ADMYRE clinical trial, where the efficacy and safety of Aplidin® with dexamethasone versus dexamethasone alone in patients with relapsed/refractory multiple myeloma after at least three, but no more than six, prior therapeutic regimens was evaluated. The results of the ADMYRE study showed a statistically significant 35% reduction in the risk of progression or death over the comparator. The study met its primary endpoint.

Multiple myeloma is a type of blood cancer which represents 10% of all haematological malignancies.

Aplidin® has so far received orphan drug designation by the European Commission and the US Food and Drug Administration.  

PharmaMar expects an answer from the regulatory agency for the second half of 2017.   

AstraZeneca withdraws EU application for experimental cancer drug approval

by Amy Schofield 22. September 2016 11:34

AstraZeneca has reportedly withdrawn an application for European approval to market its experimental cancer drug, cediranib, in combination with chemotherapy, to treat ovarian cancer.

The application is reported to have been pulled because of questions raised at a late stage by regulatory authorities reviewing the product.

The British pharmaceutical company originally sought approval from the European Medicines Agency in June 2015 to sell the treatment for use with platinum-based chemotherapy in adults with a type of ovarian cancer that’s relapsed.

AstraZeneca said on Wednesday that their VEGFR inhibitor cediranib remained an important pipeline medicine and that the decision did not affect its ongoing development in tests in combination with its approved ovarian-cancer treatment Lynparza and the experimental durvalumab cancer therapy. 

A company spokesperson said: “Following lengthy engagement with the EMA, it was clear that there would remain a difference of opinion on the overall benefit-risk of cediranib and on some of the study methods. On balance, we decided to withdraw the application for combination with chemotherapy to focus our attention on combination studies of cediranib with other medicines.”

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CHMP gives nod to Lilly's olaratumab in combination for advanced soft tissue sarcoma

by Amy Schofield 20. September 2016 15:28

Eli Lilly and Company has announced that the European Medicines Agency's (EMA) Committee for Medicinal Products for Human Use (CHMP) has issued a positive opinion recommending the granting of a conditional marketing authorisation for olaratumab, in combination with doxorubicin, for the treatment of adults in the European Union (EU) with advanced soft tissue sarcoma (STS) not amenable to curative treatment with radiotherapy or surgery and who have not been previously treated with doxorubicin.

If approved, olaratumab will be marketed under the trade name LARTRUVO™. 

This is the first regulatory step in the world towards approval for olaratumab. The CHMP reviewed olaratumab under EMA's accelerated assessment programme and the positive opinion is now referred for final action to the European Commission, which grants marketing authorisation in the EU.

An EC decision on marketing authorisation is expected within two to three months of the CHMP issuing its recommendation.

This will be Lilly's first conditional approval in the EU. As part of a conditional marketing authorisation, Lilly will need to provide results from an ongoing Phase 3 study, ANNOUNCE, which is fully enrolled. Until availability of the full data is made, the CHMP will review the benefits and risks of olaratumab annually to determine whether the conditional marketing authorisation can be maintained.

Dr Richard Gaynor, senior vice president of product development and medical affairs for Lilly Oncology, said: "Advanced soft tissue sarcoma is a rare disease that is difficult to treat, and this milestone brings us one step closer to providing physicians in Europe with a new option that they can offer to their patients."

The EU submission is based on data from Phase 2 JGDG, an open-label, randomised trial that compared olaratumab, in combination with doxorubicin chemotherapy, to doxorubicin alone in patients with advanced STS not amenable to curative treatment with surgery or radiotherapy and who have not been previously treated with doxorubicin. Efficacy endpoints included progression-free survival, overall survival and objective response rate. 

The EMA previously granted olaratumab with Orphan Drug Designation for the treatment of soft tissue sarcoma in the EU.

Sanofi and Regeneron's rheumatoid arthritis drug accepted for EU regulatory review

by Amy Schofield 10. August 2016 08:15

Sanofi and Regeneron's new rheumatoid arthritis therapy, sarilumab, has been accepted for European regulatory review.

The European Medicines Agency has accepted the companies' marketing authorisation application for the investigational human monoclonal antibody.

Sarilumab works by targeting the IL-6 receptor and has been developed for the treatment of adult patients with moderately to severely active rheumatoid arthritis.

The therapy has so far successfully been trialled in seven phase III studies, involving in excess of 3300 adult patients, most of whom had failed to respond to previous treatment regimens.

Sanofi Genzyme, the specialty care global business of Sanofi, will commercialise sarilumab if it is authorised. 

A biologics licence application for sarilumab was also accepted for review by the US Food and Drug Administration during the first quarter of 2016. A decision is expected in the next few months. 

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General | News

EMA and FDA accept Roche's MS therapy for review

by Amy Schofield 29. June 2016 15:36

The European Medicines Agency (EMA) and U.S. Food and Drug Administration (FDA) have accepted Roche's OCREVUS® (ocrelizumab) for review.

The EMA has validated Roche's Marketing Authorisation Application (MAA) of OCREVUS® (ocrelizumab) for the treatment of relapsing multiple sclerosis (RMS) and primary progressive multiple sclerosis (PPMS) in the European Union (EU). Validation confirms that the submission is complete and signifies the MAA is under review by the EMA’s Committee for Medicinal Products for Human Use (CHMP). The U.S. Food and Drug Administration (FDA) has also accepted for review Roche’s Biologics License Application (BLA) for OCREVUS for the treatment of RMS and PPMS, and has granted the application Priority Review Designation with a targeted action date of 28 December 2016.

If approved by the EMA and FDA for both indications, OCREVUS would be the first and only treatment for both forms of multiple sclerosis (MS), which affect approximately 95% of people at diagnosis.

OCREVUS is the first investigational medicine to significantly reduce disability progression in people with relapsing and primary progressive forms of MS.

Dr Sandra Horning, chief medical officer and head of Global Product Development, said: “We will continue to work closely with the EMA and FDA to bring this investigational medicine to people with MS as quickly as possible.”

The OCREVUS marketing applications are based on positive results from three Phase III studies, which met primary and key secondary endpoints.

AOP Orphan Pharmaceuticals announces progress of pivotal phase III trial

by Admin 5. March 2015 17:18

AOP Orphan has announced completion of recruitment of its pivotal phase III trial PROUD-PV ( to support global licensure of Ropeginterferon alfa 2b.

Ropeginterferon alfa 2b is a novel, long-acting, mono-pegylated Interferon, administered once every 14 days, after achieving therapy response only monthly.

Based on previous phase I/II trials, Ropeginterferon alfa 2b is expected to be safe and effective in the majority of PV patients.

Haematological and molecular responses occurred in most patients, while several patients achieved undetectable mutated JAK2 levels and a complete normalisation of their chromosomal make-up.

Ultimately, this is expected to result in improved tolerability, convenience and compliance and, as a consequence, better long-term treatment outcomes.

Design and endpoints of this trial have been discussed and agreed with both the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA), to support global licensure of Ropeginterferon alfa 2b, which also has Orphan Drug status in both Europe and the USA.

AOP Orphan has exclusively licensed Ropeginterferon alfa 2b for development and commercialisation in the field of Myeloproliferative Neoplasms (MPNs) from Pharmaessentia Corp. a biotech company based in Taiwan for European, CIS, and Middle Eastern markets. Pharmaessentia retains the rights for development and commercialization of P1101 in other major markets, such as North America, Asia, and South America.

Since its commencement in October 2013 over 260 PV patients have been recruited in 50 centres across Europe. Enrolment of patients was successfully completed in February 2015.

Treatment with Ropeginterferon alfa 2b is expected to be safe and effective in the majority of patients and to be superior to hydroxyurea.

Professors Jean-Jacques Kiladjian from Paris and Heinz Gisslinger from Vienna said: “We already know from several smaller studies that interferons work effectively against myeloproliferative diseases.”

Dr. Rudolf Widmann, CEO of AOP Orphan, said: “The unparalleled quick uptake and progress of PROUD-PV, completing enrolment of over 260 patients in around 15 months, proves the eagerness of both patients and physicians for this new treatment paradigm.”

Janssen receives positive CHMP opinion for VELCADE® (bortezomib)

by Admin 22. December 2014 15:47

Janssen has announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has adopted a positive opinion recommending the approval of VELCADE® (bortezomib) for use in Mantle Cell Lymphoma.

The drug has been recommended in combination with rituximab, cyclophosphamide, doxorubicin and prednisone, for the treatment of adult patients with previously untreated mantle cell lymphoma (MCL) who are unsuitable for haematopoietic stem cell transplantation.

The positive opinion of the CHMP was based on data from the Phase 3 study, LYM-3002. In the European Union (EU), VELCADE is currently indicated for the treatment of multiple myeloma (MM), another rare blood cancer, either as monotherapy or in combination with of other treatment regimens.

MCL is a rare and aggressive type of blood cancer that can be challenging to treat and is associated with a poor prognosis.

Thomas Stark, Vice President, Medical Affairs, Janssen Europe, Middle East and Africa (EMEA), said: "At Janssen, we are committed to continuously developing therapeutic solutions to treat relevant, haematologic diseases like MCL.

"This positive opinion brings us one step closer to offering additional treatment options with VELCADE for patients and physicians, and we are delighted with this recommendation."

The CHMP's positive opinion will now be reviewed by the European Commission, which has the authority to grant a label extension for medicines in the European Economic Area. A final decision on VELCADE's use in MCL by the European Commission is anticipated early next year.


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