Monthly Archives: April 2009

Over £220 million to boost innovation in the NHS

I went to an event last night and heard of this recently announced fund, but it had been lost in the press due to the Swine Feaver Crisis. However its interesting reading, my understanding is that this fund will be distributed to regional management and used to drive innovation and technology ddevelopment within the NHS.

A £220 million fund will be made available to encourage innovation within the NHS, Health Minister Lord Darzi announced today, during an event at the Science Museum in London to mark the launch of ‘Innovation for a Healthier Future’, a series of initiatives to nurture and reward innovation within the NHS.

Building on the Government’s firm commitment to create an innovative health service, England’s ten Strategic Health Authorities (SHAs) will each receive £2 million this year, and £5 million in each of the following four years to support frontline NHS staff in developing innovative ideas. The cash will be invested directly into a combination of projects on the ground and at regional level, speeding up the time it takes for innovative solutions to get from design bench to NHS bedside. This will benefit patients directly and increase the quality of the care they receive.

Many innovative ideas in the NHS risk not being developed due to a lack of funding. The fund has been made available to help bring these ideas about and empower the inspiration of the 1.3 million NHS staff and their colleagues in social care who make a difference each day to people’s lives.

Lord Darzi said:

‘This announcement is a huge step forward in implementing the recommendations set out last summer in my strategy on the future of the NHS.

‘NHS staff have told me that accessing the funds to make ideas become reality can be a struggle and as a result, many great ideas never get realised. That is why I am delighted to announce that we now have a £220 million innovation fund available to get those ideas off the bench and to patient bedsides, day centres or GP surgeries.

‘We know that around 40 percent of the world’s inventions over the past 50 years originated in the UK and that the NHS is rightly recognised as a world leader in the development of innovative treatments and technologies – but we can be better at putting those good ideas into action and these funds will help do exactly that.’

The Government has also announced that alongside this funding, it has put in a place a support structure on innovation for Strategic Health Authorities, with NESTA (the National Endowment for Science Technology and the Arts) and the Young Foundation acting as advisers to SHAs in bringing about a true innovation culture. The two bodies have a proven track record in nurturing and supporting innovation and assisting organisations to turn great ideas into great improvements.

Speaking about their support to the NHS, Jonathan Kestenbaum NESTA Chief Executive said:

‘The pressures on delivering high quality healthcare have never been greater. Yesterday’s solutions to tomorrow’s problems won’t work. The SHA Innovation Fund will ensure that fresh ideas and radical thinking by frontline staff can be delivered across the NHS. NESTA has developed expertise in how to encourage innovative public services and we are pleased to be able to put this into action at the very heart of public service delivery’.

In addition, Lord Darzi announced further details of the ‘Innovation Challenge Prizes’ which will engage with innovators globally and invite them to devise exciting new ways to address key health challenges.

The prizes will be a key way in which to recognise and promote emerging best practice and the Challenges themselves will be designed to engage a wide range of NHS staff.

A panel of experts will create a shortlist of possible challenges with the exact challenges announced later this year following a public engagement process. The Panel will be assisted in its work by Trevor Baylis, inventor of the wind up radio and one of this countries top inventors.

Says Trevor Baylis, ‘Britain has an outstanding heritage in innovation, from the steam engine to the MRI scanner – we are a nation of innovators who are constantly looking for new, different and better ways of doing things. The Innovation Challenges Prizes are a fantastic opportunity to create and develop ideas that can genuinely change lives for the better.’

Alongside this new investment and support, England’s Strategic Health Authorities will also be subject to a legal duty to promote innovation and support the diffusion of innovative technologies and solutions throughout the health service.

From DoH website

If you would like more detail in this area please get in touch with Damien Bové damien.bove@idaconsultants.com

Damien Bové works as a drug development consultant (pharmaceutical or biotechnology) and regulatory consultant, we work with our clients to define a drug  evelopment target, define a drug development strategy, define a regulatory strategy or define a commercial strategy. Our clients are generally raising funds or looking to license out their technology and we help them achieve it. If you want to know more don’t hesitate to get in touch.

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New Draft FDA Guidance on Somatic Cell Therapy for Cardiac Disease

The FDA CBER (Centre for Biologics Evaluation and Research) has released some draft guidance for industry. it is intended to provide sponsors who are developing cellular therapies for the treatment of cardiac disease, with recommendations on the design of preclinical and clinical studies and on the Chemistry Manufacturing and Controls information needed for IND’s (Investigational New Drug Applications), for cellular therapies aimed at cardiac disease. The guidance also provides recommendations regarding the information that you should submit on the product’s delivery system.

The Background to this guidance is expanded upon!

Despite advances in medical and surgical therapies, heart disease remains a major cause of morbidity and mortality. There is an increasing number of patients with significant morbidity despite optimal medical management. Cardiac cellular therapies have emerged as a field designed to advance the treatment of heart disease through the regeneration of cardiac tissues.

There has been much debate about how to interpret differing data and theories on the mechanism of action of cell therapies in cardiovascular disease. This guidance appears to be an attempt to set some standards in the design of these trials.

If you want to read the full guidance click here.

If you would like more detail in this area please get in touch with Damien Bové damien.bove@idaconsultants.com

Damien Bové works as a drug development consultant (pharmaceutical or biotechnology) and regulatory consultant, we work with our clients to define a drug  evelopment target, define a drug development strategy, define a regulatory strategy or define a commercial strategy. Our clients are generally raising funds or looking to license out their technology and we help them achieve it. If you want to know more don’t hesitate to get in touch.

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PhRMA Issues Revised Principles on Conduct of Clinical Trials and Communication of Clinical Trial Results

On April the 20th the Pharmaceutical Research and Manufactures of America (PhRMA) issued a revised “Principles on Conduct of Clinical Trials and Communication of Clinical Trial Results” – These guidelines outlines a number of elements including: Principles on the conduct of clinical research, registration of clinical trials and disclosure of study result summaries. Some of the more important changes include:

Registration of Clinical Trials – PhRMA advises member companies to register on a public database timely summary information about all clinical trials that study products in patients.  PhRMA defines timely as 21 days of enrollment of the first patient in the clinical trial. (this includes phase 1 studies), the PhRMA guidance is more stringent and goes further than FDA rules.

Submission of Summary Results - As it did in its prior version, PhRMA promises to disclose summary results of all clinical trials for approved drugs, regardless of the study’s outcome.  In a major change from its prior version, however, PhRMA also promises to post timely summary results of all clinical trials if the sponsor discontinues development of the drug.  PhRMA defines timely as 12 months after the trial ends, 30 days within drug approval or a year after a company discontinues the drug development program.

Disclosure of Conflict of Interest in Articles - The revision urges sponsors to encourage physicians and researchers to disclose conflict of interest information when authoring manuscripts to medical journals.  Authors that submit a manuscript to a medical journal, according to PhRMA, should disclose “all financial and personal relationships that might bias their work,” and explicitly state whether potential conflicts exist.

Increased Qualifications Needed for Authorship – The revised Principles would make it more difficult to be listed as an author of an article in a medical journal.  These more stringent guidelines adhere to the standards of the International Committee of Medical Journal Editors.

Provision of Study Results to Investigators and Participating Patients – PhRMA directs sponsors to provide all investigators with a full summary of the study results even if an investigator does not contribute to the publication of the study.

Sponsors Right To Review – PhRMA also confirms that sponsors have the right to review manuscripts, presentations, or abstracts that result from the sponsor’s studies or use the sponsor’s data prior to publication or presentation.

If you would like more detail in this area please get in touch with Damien Bové damien.bove@idaconsultants.com

Damien Bové works as a drug development consultant (pharmaceutical or biotechnology) and regulatory consultant, we work with our clients to define a drug  evelopment target, define a drug development strategy, define a regulatory strategy or define a commercial strategy. Our clients are generally raising funds or looking to license out their technology and we help them achieve it. If you want to know more don’t hesitate to get in touch.

Nonresponder phenomenon – a huge oportunity

I have just read an excellent article by David B. Jackson, and felt obliged to comment, its in this months edition of Drug Discovery Today , and its entitled Clinical and economic impact of the non-responder phenomenon – implications for systems based discovery. It makes a number of very good points and uses them as a justification for more computer modeling and data mining of diseases and therapies, however what struck me is the economic impact and the opportunity impact of this phenomenon and how it can impact on strategic decision making and as a pharmaceutical development consultant I am always looking out for such things.
Molecular diversity is part of life and as you know this impact in drug effectiveness considerable especially in the area of cancer, we all know that many oncology drugs will just not work in many patients but in those where they do work the effects are profound. David makes the argument that these present a huge opportunity for insilico drug development projects, as the reasons for a drug not working in some patients are often investigated and there tends to be lots of data available both genetic and molecular, it all means that there is a huge well understood group of patients just waiting to have their disease tackled. Just to give us an idea of the economic attractiveness of this data he runs a few interesting calculations.

The economics of non response:

While the non responder problem afflicts all therapeutic areas, it is particularly pronounced in clinical oncology, in 2006 for example the top 15 selling onco-therapeuics generated sales of approximately US$26.43billion. Within this group of drugs the average un-weighted overall response rate is 35%, the economic implications of this are massive. Estimates are that 65% of cancer patients do not response to conventional therapeutic options. so new drugs tend to grow the market rather than replace other existing therapies.
All of this means that there is a massive opportunity in many cancer indications and the level of data, both molecular and genetic should be making the job of designing new therapies an attractive option to in silico  development experts.

In summary the story is – Drug = non responder = opportunity + data

If David is to be believed we should all be reaching for our silver platters, I for one am not completely convinced that its as simple as that but I am sure all this is creating huge opportunities with the skills and backing to take advantage of it, combined with the psuh to publish unsucessful studies its all looking good.

If you would like more detail in this area please get in touch with Damien Bové damien.bove@idaconsultants.com

Damien Bové works as a drug development consultant (pharmaceutical or biotechnology) and regulatory consultant, we work with our clients to define a drug  evelopment target, define a drug development strategy, define a regulatory strategy or define a commercial strategy. Our clients are generally raising funds or looking to license out their technology and we help them achieve it. If you want to know more don’t hesitate to get in touch.

Glaxo and Pfizer to Merge HIV Drug Units in New Company – Breaking News

This has just surfaced today,  GlaxoSmithKline plc and Pfizer inc plan to combine their HIV-drug units into a new company that will control almost 20 percent of the market for anti-HIV drugs. The ownership split will be 85/15 in favour of GSK. The final ownership ratios will vary depending upon the outcome of products in development. This is a symptom of the poor outlook for both these companies in this area, with GSK’s Combivir loosing patent protection in 2012, and Pfizer is rumoured to be looking at exiting this entire area. This deal is expected to have a detrimental impact on GSK’s cash flow for the coming financial year so it remains to be seen how the markets will react to it, it looks more like a buy out by GSK than a merger in thsi authors opinion, nothing wrong with that though.

The company will have 11 of agents on the market including  Combivir and Epzicom (with combined sales of approximalty GBP £1.51bn (US$2.25bn), and Pfizer’s Selzentry will be boosted by access to the GSK’s HIV marketing infrastructure. The company will have an estimated 17 product in its development pipeline, four of which are in phase 2 development. it should be in a strong position in the area but this author wonders about risk loading an organisation around a single (high risk) indication.

If you would like more detail in this area please get in touch with Damien Bové damien.bove@idaconsultants.com

Damien Bové works as a drug development consultant (pharmaceutical or biotechnology) and regulatory consultant, we work with our clients to define a drug  evelopment target, define a drug development strategy, define a regulatory strategy or define a commercial strategy. Our clients are generally raising funds or looking to license out their technology and we help them achieve it. If you want to know more don’t hesitate to get in touch.

FDA go Mystery Shopping

Institutional Review Boards are charged with monitoring clinical trials that go through the institution to ensure patients safety and to ensure the principles for good clinical research are maintained. The FDA has decide to monitor the quality of the decisions being made by some IRB’s in commercial research institutes, in what appears to be a break from the normal methods of Audit, where they review past decisions, in the case of Coast, a for profit Independent review board, the FDA submitted a bogus clinical trial protocol, for a fictitious product and fictitious company, when the board approved the study the FDA sprang its trap. Now Coast are facing some very difficult questions, shedding staff and shedding business.

Mystery shopper is a different path but this author asks where will they take it next, fake safety reports, fake adverse event reports, its the natural evolution of the Audit.

If you would like more detail in this area please get in touch with Damien Bové damien.bove@idaconsultants.com

Damien Bové works as a drug development consultant (pharmaceutical
or biotechnology) and regulatory consultant, we work with our clients
to define a drug development target, define a drug development
strategy, define a regulatory strategy or define a commercial strategy.
Our clients are generally raising funds or looking to license out their
technology and we help them achieve it. If you want to know more don’t
hesitate to get in touch.

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Priority Review Vouchers – and there off

Some time ago we published an article about Priority Review Vouchers and how they could potentially be worth US$300million, although I have just read an estimate of US$50 to US$500 million. Well it has started now watch this space,Yesterday the FDA announced the approval of Norvartis’ combination drug product Coartem (artemether, lumefanterine) for the treatment of acute uncomplicated malaria infections in adults and children weighing at least five kilograms, and the FDA has awarded them a priority review voucher. It remains to be seen if they sell it on, for the estimated millions, or use it to speed up their own products.

For those of you who don’t know about these vouchers, how they work is if you develop a new drug against certain tropical diseases (there is a list available) the FDA gives you a voucher that can be used to grant an accelerated approval process to any product, a voucher that can be sold on. Because these vouchers if applied to a potential block buster can bring forward your access to market by at least 4 months, combined with shorter remaining patent lives on new drugs leaving development, they are expected to be worth many millions of dollars, as mentioned above values of US$500 million are being banded about.

This is obviously quite disruptive to business strategy, it could be possible to take a drug all the way to registration in a rare tropical disease with grants and charity contributions, reducing the amount needed to be raised and boosting your remaining equity well beyond what would normally be expected, then get your voucher, sell it for the many millions to fund your programmes in western disease. Its a strategy that will add significant time to your development programme but you will be sitting on the equity but its a strategy to be considered and there are many others.

If you would like more detail in this area please get in touch with Damien Bové damien.bove@idaconsultants.com

Damien Bové works as a drug development consultant (pharmaceutical or biotechnology) and regulatory consultant, we work with our clients to define a drug development target, define a drug development strategy, define a regulatory strategy or define a commercial strategy. Our clients are generally raising funds or looking to license out their technology and we help them achieve it. If you want to know more don’t hesitate to get in touch.

Pediatric Exclusivity After Product Approval; FDA Interpriations About Which You Might Not Be Aware

This is a very interesting article that raises some good points well worthy of consideration published on FDA Law Blog run by Hyman, Phelps & McNamara, In summary the FDA grants an additional period of exclusivity for a licensed product for a period of 6 months, if the sponsor submits requested information relating to the use of the active moiety in the paediatric population. There are a number of rules and regulations involved in obtaining this exclusivity (perhaps a full article on this subject is justified – I will try and get one in this week). However what this interesting article points out is that the FDA’s interpretation of the benefits goes beyond what you may think and their points of view are justified with case studies.

FDA statement

“Pediatric exclusivity will attach to exclusivity and patent protection listed in the Orange Book for any drug product containing the same active moiety as the drug studied and for which the party submitting the studies holds the approved new drug application (505A(a) and (c)).  For studies conducted on an unapproved drug, pediatric exclusivity will also attach to any exclusivity or patent protection that will be listed in the Orange Book upon approval of that unapproved drug.  FDA will attach pediatric exclusivity to protections listed at any time for a drug product as approved at the time pediatric exclusivity is obtained, as described further in section X.C.”

FDA statement

“Previously earned pediatric exclusivity will not apply to new patents or exclusivity covering later-filed applications or supplements containing the same active moiety for which a sponsor previously earned pediatric exclusivity, unless the data that earned the prior pediatric exclusivity is essential to approval of the new application or supplement.”

Interesting interpretation:

When the FDA issues a Paediatric Written Request (PWR) for a drug product that is a racemic mixture, any pediatric exclusivity granted as a result of that PWR applies not only to the to the racemic mixture but also to the sponsors other products containing either enantiomer whether or not FDA’s PWR specifically identifies each enantiomer in the racemic mixture.

previously earned pediatric exclusivity can apply to certain new Orange Book-listed patents if those patents relate back to the drug product when pediatric exclusivity was granted.

If you would like more detail in this area please get in touch with Damien Bové damien.bove@idaconsultants.com

Damien Bové works as a drug development consultant (pharmaceutical or biotechnology) and regulatory consultant, we work with our clients to define a drug development target, define a drug development strategy, define a regulatory strategy or define a commercial strategy. Our clients are generally raising funds or looking to license out their technology and we help them achieve it. If you want to know more don’t hesitate to get in touch.

GMP for phase 1, or not GMP as the case may be.

The FDA has set a trend towards the reduction of Good Manufacturing Practice (GMP) regulation in phase 1 clinical trials with the publication of guidelines “CGMP for Phase 1 investigational drugs”, this was published in July 2008, but we through it worth mentioning again for reasons that will become clear shortly. Not being a GMP specialist my interpretation is based on a read through the guidelines and comment for other experts in the field. In summary the guidance is that you can manufacture to GMP but without all the documentation that accompanies GMP, its not a return to investigators making drugs in an academic laboratory and giving them to patients, but it does significantly reduce the burden and more importantly the cost of preparing drugs for Phsae1 clinical trials.

Drug regulators are a pragmatic bunch and this is just another example of that good sense being applied, but why bring it up again, well as you all know the European Clinical Trials Directive (ECTD) has brought GMP to European phase 1 clinical trials, however word is starting to spread that Belgium and Holland and some other ECTD countries are interpreting GMP requirements for phase 1 clinical trials in a slightly different way, more along the lines of the US guidelines, and this author wonders if we might see a more “official” relaxing of the stance in Europe.

If you would like more detail in this area please get in touch with Damien Bové damien.bove@idaconsultants.com

Damien Bové works as a drug development consultant (pharmaceutical or biotechnology) and regulatory consultant, we work with our clients to define a drug development target, define a drug development strategy, define a regulatory strategy or define a commercial strategy. Our clients are generally raising funds or looking to license out their technology and we help them achieve it. If you want to know more don’t hesitate to get in touch.

New FDA Draft Guidance – Non Clinical evaluation for Anticancer Pharmaceuticals

The FDA has produced some draft guidance aimed at establishing an internationally accepted objectives and / or recommendations on the design and conduct of nonclinical studies to support the development of anticancer pharmaceuticals in patients with advanced disease and limited therapeutic options.

Because malignant tumours are life-threatening, the death rate from these diseases is high, and existing therapies have limited effectiveness, it is desired to provide new effective anticancer drugs to patients more expeditiously. Nonclinical evaluations are intended to 1)identify the pharmacological properties of a pharmaceutical, 2) establish a safe initial dose and 3) understand the toxicological profile.

These new guidlines only apply to pharmaceuticals intended to treat cancer in patients with late stage or advanced disease regardless of the route of administration, including both small molecule and biotechnology-derived pharmaceuticals.

Studies to support nonclinical evaluation

Pharmacology – prior to phase I studies, preliminary characterization of the mechanism(s) of action, resistance, and schedule dependencies as well as anti-tumour activity should have been made. appropriate models should be selected based on the target and mechanism of action but need not be studied using the same tumour types intended for clinical evaluation. these studies can provide proof of principle, guide schedules and dose escalation schemes, provide information for selected test species, and aid starting dose selection.

Safety Pharmacology – as assessment of vital organ function should be available before initiation of clinical studies. Stand alone safety pharmacology studies need not be conducted to support studies in pateiutne with late stage cancer or advanced disease.

Pharmacokinetics – the evaluation of limited kinetic parameters, e.g. peak plasma levels, AUC and half life in the animal species used for non-clinical studies can facilitate dose escalation during phase I.

General Toxicology – The primary objective of Phase I clinical trials in patients with cancer is to assess the safety of the pharmaceutical. This can include dosing to a maximum tolerated dose (MTD) and dose limiting toxicity (DLT). Therefore, determination of a no observed adverse effect level (NOAEL) or no effect level (NOEL) in the toxicology studies is not considered essential to support clinical use of an anticancer pharmaceutical. To support Phase I clinical trials at least one nonclinical study should incorporate a recovery period at the end of the study to assess for reversibility of toxicity findings or the potential that toxicity continues to progress after cessation of drug treatment. Toxicokinetic evaluation should be conducted as appropriate.

Reproduction Toxicology – These studies are not considered essential to support clinical trials intended for the treatment of patients with late stage or advanced cancer. These studies are also not considered essential for pharmaceuticals which target rapidly dividing cells in general toxicity studies or belong to a class which has been well characterized in causing developmental toxicity. Generally no fertility study is warranted to support the treatment of patients with late stage or advanced cancer. A peri- and postnatal toxicology study is generally not warranted to support the treatment of patients with late stage or advanced cancer.

Genotoxicity – Genotoxicity studies are not considered essential to support clinical trials for therapeutics intended to treat patients with late stage or advanced cancer.

Immunotoxcity – For anticancer pharmaceuticals the design components of the general toxicology studies are considered sufficient to evaluate immunotoxic potential and support marketing.

The guidelines go on to describe how you can use the pre-clinical data in designing you clinical trial: start dose for first administration in man, dose escalation and the highest dose in clinical trials. the guidelines also provide guidance on duration and schedule of toxicology studies to support initial clinical trials, the duration of toxicology studies to support continued clinical development and marketing, how to manage combination pharmaceuticals and Finlay the non clinical studies to support trials in pediatric populations. Other considerations addressed in the guidelines include conjugated agents, liposomal products, evaluation of drug metabolites, and evaluation of impurities.

Table – Example schedules for anticancer pharmaceuticals to support initial clinical trials. (reproduced from FDA guidelines S9)

moz screenshot 1 New FDA Draft Guidance   Non Clinical evaluation for Anticancer Pharmaceuticals

table1 300x182 New FDA Draft Guidance   Non Clinical evaluation for Anticancer Pharmaceuticals

If you would like more detail in this area please get in touch with Damien Bové damien.bove@idaconsultants.com

Damien Bové works as a drug development consultant (pharmaceutical or biotechnology) and regulatory consultant, we work with our clients to define a drug development target, define a drug development strategy, define a regulatory strategy or define a commercial strategy. Our clients are generally raising funds or looking to license out their technology and we help them achieve it. If you want to know more don’t hesitate to get in touch


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