Tufts Center: Approval Times Have Dropped, But Is It Enough?

For those of us who work in and follow the drug industry, winter is always made a bit brighter and warmer with the coming of the annual Outlook paper by the Tufts Center for the Study of Drug Development. The Tufts report is one of the definitive measures of where we are, where we're heading, and what hoops we have to jump through to get there.

This year's report (here's the Center's summary; the full Outlook 2010 will be made available to non-subscribers this spring) has plenty to chew on, but here are a few of the more relevant points that drug developers and QbD professionals need to consider:

--Few drugs make it to market, but it's important to remember that of those that do, only 3 of 10 generate enough revenue to sustain R&D.
--Drug developers don't just need to improve time to market, they need to dramatically change what they're doing--to "transform the way they conduct research and development over the medium and longer term to be more efficient and productive."
--Collaboration is critical. R&D success will depend upon how developers engage their partners at critical points in the product lifecycle.
--Risk management will continue to balloon in importance. With FDA and global regulators limited in their resources, it will be left up to developers to show expertise via Risk Evaluation and Mitigation Strategies (REMS)
--Biotech products will boom, but take longer to get to market due to increased clincial trial requirements.

Just a few thoughts to warm your winter.

In the EU, Funding for Those Who Strive to Eliminate Bottlenecks

The Innovative Medicines Initiative, a project started jointly by the EC and EFPIA, has announced another round of funding for projects that aim to speed drug development, including those that solve data management dilemmas. Click here for more.

Are You Innovating and Imaginating All By Yourself?

One of the many people I spoke with this past week at the AAPS show in Los Angeles was Ted Grasela, CEO of Cognigen Corp., which advises manufacturers on model-based drug development. Grasela delivered a presentation on the importance of modeling and simulation to development, and on strategies that pharmacometricians and statistical experts can use to influence drug development in a positive way. It's time for modeling and simulation to take its rightful and significant place in drug development decisionmaking, Grasela said.

Most importantly, statistical modeling can be a kind of glue that binds the entire drug development process and the people involved. “People are innovating and imaginating all over the place," Grasela says, "but often these islands of innovation that never get linked with one another.”

Here's my full writeup of Grasela's presentation. I stopped by the Cognigen booth afterwards for a chat with Grasela and Cognigen colleagues, and came to appreciate their ideas of bringing more science to the development process. Here's the Cognigen home page for those interested.

The Henry Ford of Drug Development? Have We Heard This One Before?

Quote of the day: "This device is to drug discovery what the assembly line was to the automobile or the silicon chip to information technology." I'm sure this device to inject proteins into cells to accelerate drug development is useful, but could this McMaster U. researcher be prone to just a bit of exaggeration?

Push vs. Pull: Finding Better Ways to Incentivize Development of Antibiotics

There's an excellent, balanced summary of the pros and cons of "push" and "pull" forms of incentivizing drug development (focused on antibiotics), by Kurt Karst on the FDA Law Blog. Karst quotes and links to a London School of Economics paper that urges governments to take more proactive roles in working with industry to establish viable incentives for those who develop promising antibiotic medicines, in light of "superbugs" and the issue of resistance to current antibiotics.

The report itself is exhaustive but worth a look. Don't be put off by the "Confidential" label at the bottom of each page, since the PDF is easily found in many places on the web.

Should We Call It an ELNLIMS?

We won't call it the holy grail, but the announcement by Thermo Scientific and Symyx regarding the release of an integrated LIMS/ELN product is a significant step towards a fully integrated, electronic laboratory. Researchers should have more power and functionality at their fingertips, with fewer obstacles towards accessing and sharing data. That spells more efficient development efforts.

In a press release last spring announcing the Thermo-Symyx partnership, Symyx president Trevor Heritage boasted that lab professionals will have the “ability to record and execute experimental protocols, capture results, access and analyze data, build reports and collaborate with colleagues seamlessly."

Given that it's now just six months since the partnership was announced, clearly there will be bugs to be worked out of the new offering, but that's to be expected.

Another intriguing question: What do we call something that combines a three-letter and four-letter acronym? ILMS (Integrated Lab Management System)? I'll have a chance to speak with representatives of both

Lessons Learned from 20 Years of Drug Development

Have the past 20 years been a bit hazy for you, or perhaps you'd just like a reminder of what we've learned from drug development's successes and many failures? Deloitte is hosting a free webinar on Nov. 10 on the lessons of the past couple decades.

--Paul Thomas

The Challenges of Developing Alzheimer's Therapies

A quick note: From this month's Nature, an insightful look at the complexity of Alzheimer's Disease and the challenges (and limitations) of developing drugs that target the disease early enough in its progression to make a difference.

--Paul Thomas

Studying Dogs Alongside Humans, to Develop Cancer Drugs for Both

National Cancer Institute researchers are undertaking a project to conduct comparative oncology drug trials in humans and dogs, with the hopes of providing an improved perspective upon how clinical drugs will perform in later-stage trials. An offshoot of the project is to accelerate the development of efficacious cancer drugs for dogs. The Comparative Oncology Trials Consortium maps out its mission in the Public Library of Science online. Here is some of the rationale behind their work:

Current drug development pathways are frequently unidirectional. Novel agents are assessed in conventional preclinical models of efficacy and toxicity before moving into human clinical trials where they either fail or succeed. Particularly with novel targeted therapies the conventional paradigms of toxicity studies conducted in healthy animals followed by Phase I and Phase II human trials leave unanswered many important questions on the “best use” of these drugs [6]. Translational drug development studies in pet dogs with cancer provide an opportunity to answer these questions by serving as an intermediary between conventional preclinical models and human clinical trials [7]–[9]. In these dogs, cancers develop naturally in the context of an intact immune system and with a syngeneic host and tumor microenvironment. Similar environmental, nutrition, age, sex, and reproductive factors lead to tumor development and progression in human and canine cancers. They share similar features such as histologic appearance, tumor genetics, biological behavior, molecular targets, therapeutic response, and unfortunately, acquired resistance, recurrence, and metastasis.

--Paul Thomas

S-P'S Hassan: Small Developers Losing Clout, and Risk Losing Innovative Spirit

Speaking recently, Schering-Plough's Fred Hassan lamented the fact that small drug developers are not only seeing their market valuations decline, making them easier, less expensive takeover targets, but also that they face the prospect of losing their "innovation power" once they are swallowed up by larger companies. The comments were part of a longer speech by Hassan on the need to create more flexible pathways to bring cancer and other critical drugs to market sooner.

--Paul Thomas

What Lessons Will We Take Away from H1N1 Vaccine Development and Approvals?

Cutting Edge Information specializes in paid research reports for pharmaceutical decisionmakers, but yesterday sent out a press release not plugging a new report but simply opining on what lessons will be learned from the rapid and, it appears, successful development of new vaccines to tackle the swine flu pandemic. And what's to be gleaned from how quickly these drugs were approved by global regulators?

CEI raises some salient issues: if H1N1 vaccines can be successfully fast-tracked, shouldn't this open the door for more rapid and favorable regulatory review of oncology drugs and other products that clearly

Global Outsourcing of Clinical Trials: Patient Concerns and Hope for Change

I've seen a number of news items come across my desk of late about Western companies forging partnerships to outsource clinical trials around the globe, particularly to India. Today's OpEd piece from UK's Guardian looks at some of the growing concern over fair treatment of patients as this trend plays out. The primary concern: "informed consent" can look good on paper but not necessarily be honored and practiced in situations in which trial patients are severely economically disadvantaged.

There are positives about the continued trend towards outsourcing trials overseas, of course. It's an opportunity to speed drug development, and to increase the availability of medications for "local diseases" around the world.

--Paul Thomas

U.S. vs. EU: Who's Better at Getting Drugs to Market? Does It Matter?

Joseph DiStefano of the Philadelphia Inquirer looks at the recent research of Dr. Donald Light, a visiting professor at Stanford, with an eye towards the debate over whose system of drug development, Europeans' or Americans', is the more productive.

Light reassesses the work of researchers Henry Grabowski and Richard Wang, who concluded a few years back that enhanced free-market conditions in the U.S. had allowed pharma and biotech companies here to get more drugs to market more quickly.

Not so fast, says Light. In his work, Light figures in the sheer amount of money spent on development (much higher in the U.S.) and whether or not the drugs that got to market really made a difference beyond what drugs were already available to consumers--or, as is often the case, they simply added one more product to the mix.

Dollar for dollar, Light says, and despite more prevalent government cost controls, European development is the more efficient system. (PhRMA wholeheartedly disagrees, as DiStefano's article notes.)

Regardless of which side of the pond you're on, and which public-private system of drug development you lean towards, the research from Grabowski, Wang, Light, et al. points to a greater need, everywhere, for increasing the quality and efficacy of drugs approved. Says Light about the U.S., "only about one in seven new drugs are better than existing drugs." Even if you question his methods, motives, or accuracy, it's a sobering statistic to consider, and a reminder that Quality by Design thinking is needed to keep our attention on what's important--getting truly better drugs to market, faster and cheaper than before, everywhere in the world.

--Paul Thomas

Drug Development, an Interactive Tour

Hadn't seen this video before on PhRMA's Innovation.org web site, but it's well done. A bit sappy (cue the piano music), but it's a good step-by-step look at how drugs get to market. A good one to send all your friends and relatives who wonder: a) how drugs get to market; and b) why it takes so darn long to get there. It's also good for explaining to them what you do--e.g., "See that guy talking about submitting IND's to the FDA--that's what I do all day!"

--Paul Thomas

Putting a Dollar Value on Pharmacogenomics

Few would argue that pharmacogenomics (using genomic markers to predict drug response in patients) will play a role in targeting drug leads and getting compounds to market faster. Researchers (consultants with NERA consulting and the University of North Carolina) have taken steps to quantify the impact that pharmacogenomics could have. The greatest economic benefits could result from the ability of pharmacogenomics to identify successful preventative medicines and thereby reduce overall healthcare costs, the researchers say in their new report on the economics of pharmacogenomics. They also suggest that their work justifies giving pharmaceuticals a larger slice of the overall healthcare financing pie. The full report can be downloaded free of charge.

--Paul Thomas

What Is the Real Meaning of Pharma Innovation?

Britain’s NICE (National Institute for Health and Clinical Excellence) is charged with providing guidance on promoting good health among citizens of the U.K. Unfortunately, NICE has had a contentious relationship with the drug industry in general, and has often been viewed not as a promoter of public health but rather an impediment to innovation which might benefit the public. One way to put it: “Pharma sees NICE as a barrier to its ambitions to bring products to patients. NICE sees itself as the guardian of the public purse and of all patients.”

The above statement is from Sir Ian Kennedy, who was hired by NICE earlier this year to review the organization’s procedures and make recommendations for how it might turn things around—i.e., “make nice” with pharma while still protecting the public interest. Kennedy has issued his final report, "Appraising the Value of Innnovation and Other Benefits," with a laundry list of recommendations for NICE. But, for those of us outside the U.K., we might find most compelling Kennedy’s ruminations on the meaning of innovation within a pharma context. Here are some of those thoughts, from the report:

“ . . . It will come as no surprise that, while everyone was content to use the word [innovation], and everyone agreed that it was a good thing, it was not easy to identify what was being discussed. In fact, as is common in policy-making, the absence of any hard centre of meaning allows people from all quarters to appear to be in agreement, without the need to nail down what it is that they were agreed on.

4.8 There is no shortage of definitions of innovation. Their very number suggests an amorphous concept. It is clear to me that the notion of innovation has a range of connotations which are, to a degree, context-specific. And, the world of pharmaceutical products is one such context. As a first step, it may help to know what Sir David Cooksey had in mind when he called for this study. When I spoke to him he referred to innovation as connoting “different ways of doing things which bring improved outcomes”. This helps. There is the idea of difference, or newness, and the idea that it represents an improvement on what went before. . . . it should be clear that something more than newness (or difference) plus some degree of improvement in effectiveness may be necessary to qualify as innovation in this specific context. . . .

4.10 Where innovation becomes important, therefore, is when Pharma states that a product meets three initial criteria, in that the product: But, they will not warrant any special treatment. Only if they are priced in a way that meets NICE’s established approach, will they warrant approval. Such products may be described as innovative, but the claim alone will cut no ice, nor bring any special treatment.
• is new
• constitutes an improvement on existing products
• offers something more: a step-change in terms of outcomes for patients

Kennedy agrees that “step-change” is in itself amorphous as well, but this is what we should by striving for as an industry, and this is the concept around which NICE and pharmaceutical companies can coalesce to expedite products to market that are truly “innovative.”

--Paul Thomas

On the Horizon: Drug Discovery and Development Week

Drug Discovery and Development Week, a collection of five conference themes around one exhibition, is slated for the first week of August in Boston. Among the highlights: In the Drug Safety Strategies to De-Risk Compounds event, William Mattes, former director of toxicology for the Critical Path Institute, will deliver a keynote on Skirting Drug Safety Potholes in the Critical Path to POC, while FDA senior scientific advisor Wendy Sanhai will discuss Biomarker Development and Clinical Qualification. The Cancer Drug Development track will feature a debate on the effectiveness of current methods of development via cancer stem cells. There's plenty more on hand, of course, including a keynote by Daiichi Sankyo president and CEO Takashi Shoda, on the challenges of building a global drug company in today's market.

--Paul Thomas

Progressive Collaborations: GSK Gets First Contributor to Patent Pool

Another exciting collaboration speeding development: Alnylam has become the first company to jump into the patent pool that GSK has established to aid development of drugs to confront tropical diseases. Alnylam will contribute some 1,500 current and pending patents, tripling the number that GSK has already contributed itself.

GSK CEO Andrew Witty: “The key objective of the pool is to make it easier for researchers across the world to access intellectual property that may be useful in the search for new medicines to treat neglected tropical diseases. The more companies, academic institutions and foundations that join the pool, the more effective it will be. Alnylam’s announcement today is therefore a welcome and significant step forward.”

--Paul Thomas

Public and Private: Janssen Alliance for TB Drug Development May Serve as Model

An interesting note from a few weeks ago on an agreement between Janssen subsidiary Tibotec and the not-for-profit TB Alliance to share resources and expertise. Says the alliance's president and CEO Mel Spigelman, “Since the TB Alliance was founded, we have assembled the largest pipeline of new TB drugs in history . . . " It's a great model for collaboration, cost sharing, and bringing needed drugs to market that otherwise would not have gotten the full resources and backing they deserve.

--Paul Thomas

Real-Time Neurochemical Monitoring of Trial Patients?

A good article in the Irish Times detailing some of the work in the Emerald Isle to speed drug development. The lead is about the work of John Lowry at the National University of Ireland Maynooth. Some of Lowry's research is available online. Here is a journal article detailing his team's efforts to enhance the selectivity of its biosensors. And here is a thorough video on Lowry and his biosensor work.

--Paul Thomas