Much Adieu about Nothing: MRSA Found at Public Beaches in Washington State

The 2009 Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) is currently taking place in San Francisco. For those of you who may not know ICAAC, is an annual meeting mainly attended by infectious disease physicians and researchers where the latest and most cutting edge research on infectious agents is reported. Things must have been a little slow at this year’s meeting (except for H1N1 of course) which led the newswires to pick up a story about the isolation of methicillin resistant Staphylococcus aureus  (MRSA) at public beaches in Washington State. While MRSA infections are certainly a public health concern, particularly among infants, older adults and immunocompromised individuals finding MRSA at public beaches isn’t particularly surprising nor newsworthy.

S. aureus is an opportunistic pathogen that isn't particularly virulent and is incapable of causing disease unless it is accidentally introduced into a wound, surgical incision or similar environment. In humans, the bacterium colonizes mainly the nasal passages, but it may be regularly found in most other anatomical locales, including the skin, oral cavity and gastrointestinal tract. Epidemiological studies have demonstrated that over 70% of people transiently carry S. aureus in their nasal passages at one time or another in their lives. This means that S. aureus is very common and ubiquitous in human populations. Consequently, I wasn’t surprised when I learned that Seattle researchers had isolated S. aureus at public beaches in Washington State. Nor was I shocked to learn that some of the isolates were MRSA strains!  After all, the incidence of methicillin-resistant S. aureus has been steadily increasing in the US and elsewhere for the past 20 years. And, healthy people who carry MRSA (and regularly shed it from their bodies) do like to go to beach and lay in the sand when the weather is warm. That said, I would have flabbergasted if the researchers didn't isolate MRSA from the beach sand samples that they surveyed. As an aside, I want to let my readers know that I isolated S. aureus from a soil sample while an undergraduate microbiology  major at Cornell University. Finally, while some MRSA infections can be fatal, those that are diagnosed correctly and early are usually easy to eliminate with conventional antibiotic regimens.

Because the work mentioned in the ICAAC press release hasn’t been published, it is  difficult to evaluate the results and implications of the study's findings.  Nevertheless, I don’t think it was prudent for the scientists who conducted the research to issue a press release about finding MRSA at public beaches—especially when the American public is already jittery about infectious agents like H1N1. If the authors’ intent was to make a big splash (pun intended) by mentioning the “dreaded MRSA” in their press release, they were successful—the story is all over the news. However, in my opinion, we are obliged as scientists to accurately inform the lay public about important scientific and public health issues—not play into its worse fears and misconceptions about them.

Until next time...

Good Luck and Good Job Hunting!!!!!!

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Cinnamon Oil: A New Antibacterial?

There are many natural products from animals, plants, fungi and bacteria that possess antibacterial properties. This makes complete sense from an evolutionary standpoint. Therefore, it should comes as no surprise that spices like cinnamon and natural products like honey possess inherent antibacterial properties. Nevertheless, despite my over 30 years as a card-carrying bacteriologist, I always pleased and pleasantly surprised when I learn that a common substance like cinnamon oil has potent antibacterial activity against antibiotic-resistant bacterial pathogens.

A recent study showed that a cinnamon oil solution was capable of killing a variety of nosocomial bacterial pathogens including Streptococcus pneumoniae and methicillin-resistant Staphylococcus aureus (MRSA). Moreover, the cinnamon oil appeared to be as effective as several antiseptics and disinfectants widely used in many hospitals. And, this isn’t the first report on the antibacterial effects of cinnamon oil. In a 2008 study, French researchers showed cinnamon oil solutions of 10% or less were effective against S. aureus, Escherichia coli and several antibiotic resistant strains of bacteria.  Further, there is a precedent for the use of cinnamon-derived products as an antiseptic. In the Middle Ages thieves who stole jewelry from dead bodies and used “thieves oil”—a concoction consisting of cinnamon bark, lemon oil and eucalyptus—rarely got ill. Finally, cinnamon oil when topically applied to the skin is generally safe. However, in some people it can cause an allergic reaction.

This is good news for a country that has grown increasingly obsessed with chemically-based antibacterial soaps and sanitizers whose overuse may actually be selecting for the emergence of strains of multiple antibiotic resistant bacteria. Nevertheless, the use of natural antiseptics like cinnamon and other plant oils as sanitizers may help to reduce the growing incidence of  drug resistance among nosocomial bacterial pathogens.

Until next time....

Good Luck and Remember to Wash Your Hands (with plain soap, not antibacterial-containing products!)

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Educating the American Public: Enough with the "Germs" Already

The media frenzy surrounding the impending H1N1 swine flu pandemic has spawned a recent spate of articles and television news segments on “germs.” In the last 48 hours, articles on germs have appeared in the New York Times, my local paper (The Trenton Times via the Chicago Tribune), on news channels and most recently this morning on the Today Show on MSNBC. Most of these have focused on where “germs” are found, how they are spread and ways to minimize or prevent their transmission. For those of you who may be interested, the word germ was first coined in 1664 and is defined as a “small mass of living substance capable of developing into an organism or one of its parts” or more conventionally, as a “microorganism that causes disease.” While these media pieces are intended to inform the public about infectious agents and their transmission, most people who read or see these reports don’t understand that the word germ can encompass viruses, bacteria and fungi. And, to make matters worse, most Americans don’t know that viruses, bacteria and fungi are different microorganisms.

Unfortunately, after reading newspaper articles and seeing reports on television about so-called germs, many consumers rush out to their local groceries and purchase a variety of antibacterial soaps and detergents—erroneously believing that these products will protect their families from infection by the dreaded H1N1 virus and other pathogens. Although frequent hand washing and the appropriate use of viricidal disinfectants can help to reduce transmission of H1N1 and other viruses, antibacterial products are generally less effective (or ineffective) against viruses and overuse can result in emergence of multi-drug resistant bacteria.

To that end, I think it is high time that the news media eschew the use of the anachronistic term germ in favor of bacteria, virus or fungi when referring to causative agents of infectious diseases. Promulgating the use of the word germ will continue to keep the lay public in the dark about infectious agents and the diseases they cause and hinder people from making informed decisions about treatment and preventing their transmission.

Until next time...

Good Luck and Good Job Hunting!!!!

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Pharma Investing Less in R&D: What Does the Future Hold?

It’s no secret that major pharmaceutical companies are no longer investing in internal drug discovery initiatives as much as they have in the past. However, I was unaware how drastic the decline in R&D spending was until I read an article entitled “Significant Change Predicted for Bioindustry” by Benjamin J. Conway in the July issue of Genetic Engineering & Biotechnology News. 

Mr. Conway notes that in 1989 more than 50% of the pharmaceutical industry’s budget was spent on preclinical drug discovery and development. During the 1990s, the percentage slowly declined and was approximately 44% by 1999. He asserts that beginning in 2000, “the drop became precipitous” as pharmaceutical companies spent increasing amounts of their R&D budgets on downstream activities including expanded clinical trials. By 2006, big pharma was spending about 25% of its budget on R&D. Strikingly, Mr. Conway contends that “when measured in terms of constant absolute dollars, spending on pre-clinical R&D activities actually declined 0.4% annually over the period, despite annual increases of nearly 7% in total R&D spending.” 

Not surprisingly, the almost decade-long decrease in pharmaceutical R&D spending is best reflected in the lack of new drug approvals over the past five years or so. According to Mr. Conway, throughout the 1990s more than 50% of all new drug approvals originated at big pharma companies. By 2001, these companies were responsible for approximately 60% of new drug approvals. However, since then, pharma’s new drug approvals have plunged to 25% to 30% of annual totals. Some analysts suggest that the figure has been as low as 15%. The decline in new drug approvals almost parallels the decrease in R&D spending at most major pharmaceutical companies. Many industry analysts and thought leaders contend that big pharma companies have gotten too big and unwieldy and can no longer innovate. The unprecedented drops in pharma’s new drug approval rates tend to support that assertion. Mr. Conway points out that the so-called “innovation gap” has been filled by biopharmaceutical companies that “today account for 75% or more of new therapeutics developed each year.”

These changing market dynamics suggests that big pharma must reconfigure the business model that it has clung to for the past 50 years to remain competitive. Not surprisingly, almost all of the major pharmaceutical companies have begun to do just that! For example, over the past three years more than 60,000 R&D scientists have lost their jobs with little likelihood that the vacated jobs will ever be resurrected. Further, big pharmaceutical companies have increasingly begun to outsource many R&D activities to Asia, Eastern Europe and elsewhere. Finally, most big pharma companies have publicly demonstrated—through mergers and acquisitions—that biotechnology products as well as small molecules are in their future.

While big pharma may be retrenching and evolving, don’t expect the pharmaceutical industry on internal drug discovery initiatives —or small molecules for that matter— to disappear any time soon. The industry is going through a transitional period and the companies of the future will look only slightly different than they do today. These companies will still be large and well capitalized, but likely more diversified in their product portfolios (which will surely contain biotechnology drugs). Also, they will continue to excel in new product development, marketing and distribution. However, unlike the past, much less emphasis will be placed on internal R&D programs to discover new molecular entities. This means that pharmaceutical R&D operations will remain lean and companies will increasingly rely on M &A and licensing deals (with smaller specialty pharma and biotechnology companies) to keep their pipelines full.

Until next time...

Good Luck and Good Job Hunting!!!!!!!!!!

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Another Sign That Pharma Companies Will Rely Less on Internal R&D Programs

The drug maker Eli Lilly and Co quietly launched a new website today for a program dubbed Lilly Phenotypic Drug Discovery Initiative or PD2. According to the company, “The PD2 initiative is a unique opportunity for investigators from external institutions to submit proprietary compounds for potential screening in Lilly's phenotypic assay panel. This highly collaborative process is enabled by a web-based application that facilitates efficient transfer of information between Lilly and the investigator. The PD2 screening panel is currently comprised of five modules which are relevant to therapeutic areas of long-term strategic interest, including oncology, neurological disorders, and metabolic diseases. This panel may change over time to reflect additional research interests.”

Company officials believe that program will allow it to evaluate and possibly license treatments from biotech companies and academic institutions "that are never fully evaluated as potential drug candidates." The launch of the PD2 website—perhaps the first of its kind—clearly sends a signal that pharmaceutical companies are reducing their reliance on internal discovery programs to identify prospective new molecular entities and are eager to enter into licensing deals to find and acquire them. 

Membership in the PD2 requires that a legal representative from the investigator's academic institution or biotech company executes a Material Transfer Agreement (MTA). Once the MTA is reviewed and approved by Lilly officials, the institution can create an account. Until that time, use of the site is limited to browsing only. I have no doubt that technology transfer offices at most major universities will be signing up for membership in short order.

I think the PD2 initiative is an innovative and timely one given the massive reductions in R&D jobs that have taken place at many pharma companies over the past two years. Expect other pharma companies to follow Lilly’s lead.

Until next time....

Good Luck and Good Job Hunting!!!!!

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The Follow-On Biologics Debate: Innovator Companies Lose Round 2

A much-anticipated Federal Trade Commission (FTC) report was released on Wednesday that will likely help House Energy and Commerce Chairman Henry Waxman bolster support for his fledgling follow-on biologics (FOB) bill. For those of you who haven’t been closely following the debate over proposed legislation to create a regulatory framework for approval of FOBs in the US, I provide a brief synopsis.

The Promoting Innovation and Access to Life-Saving Medicines Act (H.R.1427) introduced by US Representatives Henry Waxman (D-CA), Frank Pallone (D-NJ) and Nathan Deal (R-GA) calls for an abbreviated development pathway (at the discretion of the agency), the possibility of substitution or interchangeability (if the follow-on biologics manufacturer can prove a high degree of structurally similarity and an identical mode of action) and five years of data exclusivity. In contrast, The Pathways for Biosimilar Act (H.R. 1548) introduced by US Representatives Anna Eshoo (D-CA), Jay Inslee (D-WA) and Joe Barton(R-TX) requires clinical data, rigorous immunogenicity testing and limits on interchangeability and substitution provisions for follow-on biologics. Further, it calls for a minimum of 12 or up to 14 years of data exclusivity for innovator companies—a period during which FDA can’t rely on innovator data to approve follow-on biologics. For example, if a biotechnology drug was approved in 2009, the earliest that FDA could consider and approve an application for a competing follow-on product is 2021.

The FTC report concluded that a 12- to 14-year wait is unnecessary because follow-on biologics will not be offered at the same steep discounts as traditional generic drugs. It also pointed out that no evidence exists that biologic patents will not hold up. The agency estimates follow-on biologics would be sold at discounts ranging from 10 percent to 30 percent. Not surprisingly, the FTC did not recommend a specific number of exclusivity years. This allows legislators to continue to squabble and debate the point ad nauseum, until concessions are made by both innovator and follow-on biologics proponents.

The measure by Eshoo and Barton has garnered 88 co-sponsors, while Waxman and Deal's bill has 11. In the Senate, the Health, Education, Labor and Pensions Committee reached a bipartisan compromise on follow-on biologics in 2007 that allowed for 12 years of exclusivity, but that deal seems unlikely. Democrats are trying to address generic firms' concerns that brand companies could make slight changes to their products and start the exclusivity period over again. Some senators introduced a more generic-friendly bill like Waxman's earlier this year.

Conventional wisdom suggests that the data exclusivity provisions in the final legislation will be five years—a period identical to that provided stipulated in the 1984 Hatch Waxman Act, which created the US generic pharmaceutical industry. 

Stay tuned for new updates on this unfolding drama!

Until next time...

Good Luck and Good Job Hunting!!!!!!!!!! 

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Why Downsizing May Hurt Pharma

Since 2007, approximately 80,000 pharmaceutical jobs have been eliminated. The recent consolidation in the industry, e.g., Merck-Schering, Pfizer-Wyeth and Roche-Genentech suggests that many more life sciences jobs will be lost over the next year or so. Typically, to avoid law suits and possible discrimination claims, most companies will layoff a mixture of experienced and entry level employees that cover the racial, religious and age spectra. For those of you who may not know, Americans who are 40 and older constitute a “protected class of employees.” In other words, companies that layoff employees cannot disproportionately give pink slips to employees 40 years of age or older. This law was enacted because older employees typically have higher salaries and have accrued more benefits and vacation time than their more junior counterparts and eliminating them can drastically cut costs. While most companies are careful to layoff a mixture of junior and senior employees during large layoffs, a quick perusal of the demographics of employees who lose their jobs reveals that many of them are older, more experienced workers. Sacrificing a few entry level employees (to prevent any red flags) is worth it to the accountants who charged with cutting costs and orchestrating large corporate layoffs.

Unlike consumer goods, pharmaceutical and biotechnology drug development is arcane, complex and may take up to 15 years to complete. There are many “go” or “no go” decisions that must be made during the drug development process. Typically, these decisions are rendered by experienced employees who have been “down the road” many times before and are able to recognize the oft-time nuanced attributes of successful drug candidates. Without the benefit of these employee and their experiences, drug companies may struggle to make the “right decisions” for new products being developed. Also, the loss of experienced employees can disrupt the flow of essential “corporate knowledge” to entry level and more junior employees. This is important because— while most entry level and junior employees are academically and technically qualified—it usually takes them years (under the tutelage of mentors and senior employees) to understand a company’s best practices. Put simply, the unrelenting loss of experienced pharmaceutical workers can alter the standing or dominance of pharmaceutical companies in certain therapeutic areas. While massive layoffs of experienced pharmaceutical employees bolster drug stock prices in the short term, the long term effects of these layoffs on the overall health of the pharmaceutical industry remains uncertain.

Jeff Kindler, Pfizer’s CEO, mentioned yesterday during a CNBC interview, that eight Wyeth senior executives will keep their jobs after the Pfizer-Wyeth deal closes later this year. Not surprisingly, he failed to mention how many “rank and file” employees of the combined company would keep their jobs after the merger. Don’t be shocked when Pfizer-Wyeth announces massive layoffs after the deal closes—Pfizer’s stock price has fallen 21% since it announced the Wyeth acquisition late last fall.

Until next time....

Good Luck and Good Job Hunting!!!

 

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Word on the Street: Novartis May Purchase Cubist for $1.6 billion

Rumors are rife that Novartis is going to purchase Lexington, MA-based Cubist for $1.6 billion. Wall Street analysts are speculating that Novartis may announce the deal as early as Monday.

Cubist manufactures Cubicin (daptomycin), one of only a handful of new antibiotics brought to market in the past 20 years that is effective against many infections caused by Gram-positive bacteria, most notably methicillin-resistant Staphylococcus aureus (MRSA). The company is developing new lipopeptide antibiotics similar to Cubicin and also has an active anti-viral drug discovery program.

Over the past 10 years, big pharma companies largely abandoned antibiotic research and placed all discovery efforts in the hands of only a few smaller public companies and startups. Cubist is the only independent biopharmaceutical company that successfully brought a new antibiotic to market. 

Novartis’ possible acquisition of Cubist signals, that at least one major pharmaceutical company sees opportunities and upside in the antibiotic drug discovery market. Several years ago, Pfizer acquired another antibiotic discovery company, Vicuron (formerly Versicor) but to date the acquisition has not yielded any new antibiotics. While Novartis’ acquisition of Cubist is yet another sign of consolidation that is taking place in the life sciences sector, it may bolster new efforts in the antibacterial drug discovery area. Unlike Cubist, Novartis has enough money and marketing muscle to increase Cubin sales and develop some of the exciting new molecular entities in Cubist’s drug development pipeline.

Until next time…..

Good Luck and Good Job Hunting!!!!

 

Methicillin Resistant Staphylococcus aureus: A Growing Link between MRSA Infections and Pigs

That methicillin resistant Staphylococcus aureus (MRSA) is in the news again is not surprising. However, to my knowledge, Nicholas Kristof‘s article in today’s New York Times may be the first Op-Ed piece written by a non-scientist about the growing threat and seriousness of MRSA infections. Mr. Kristof apparently became aware of MRSA when he was contacted by Tom Anderson, MD, a Camden, Indiana physician who was experiencing “phenomenal levels of MRSA infections" in his community.

Beginning in the early 1990s, Dr Anderson noticed a rapidly rising incidence in the number of community acquired skin infections caused by MRSA among his patients. Most of Dr Anderson’s patients were swine farmers—the predominant industry in Camden. At first puzzled by the growing incidences of MRSA outbreaks, Dr. Anderson began to suspect that his patient’s pigs may be the source of growing number of cases of MRSA skin infections. He was reluctant to alert public health officials about his suspicions because any hint livestock-related health issues might jeopardize the livelihood of many of his neighbors and friends. By last fall, however, Camden’s MRSA epidemic had grown so large that Dr. Anderson could no longer remain silent. Rather than alert the authorities himself, he decided to invite Mr. Kristof, an investigative reporter, to visit him in Camden and break the story. Unfortunately, before Mr. Kristof could visit, Dr. Anderson died abruptly at age 54. There was no autopsy, but a blood test suggested he may have died from a heart attack or aneurysm. And—this is where the story gets interesting—a recent Dutch study has linked porcine MRSA isolates to a case of human endocarditis. Dr. Anderson had himself suffered at least three bouts of MRSA infections.

In another Dutch study conducted in 2004, MRSA strain ST398 (which caused the endocarditis in the more recent study) was isolated from three family members, three farm workers and 8 of 10 pigs from a single farm. Since then, strain ST398 has spread rapidly through the Netherlands — especially in swine-producing areas— and pig farmers there are 760 times more likely than the general population to carry MRSA. More recently, a study conducted by public health officials in Ontario, Canada showed that 20% of pig farmers were colonized by strains of MRSA genetically identical to those isolated from European pigs. Finally, a 2008 study conducted in Iowa, reported that strain ST398 was isolated from 45 percent of pig farmers and 49 percent of hogs that were tested. Together, these studies suggest that colonization of swine by MRSA and pig farmers is very common and that swine (and possibly other agricultural animals) could become an important reservoir for strains of MRSA.

While not conclusive, most infectious diseases experts believe that the emergence of MRSA and antibiotic resistant bacteria can be directly linked to the widespread and rampant use of antibiotics as growth enhancers in livestock feed. Despite the alarming emergence of multiple antibiotic resistance bacteria, livestock producers in the US and elsewhere continue to add antibiotics to livestock feeds. This led Mr. Kristof to lament that “we as a nation have moved to a model of agriculture that produces cheap bacon but risks the health of all of us.” Not surprisingly, as is frequently the case, big business has chosen to place profits before the health and safety of society.

Until next time...

 

Good Luck and Good Reading (look for Mr. Kristof’s Sunday column on the emergence of antibiotic resistant "superbugs")

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Dr. Margaret Hamburg Tapped As New FDA Commissioner

According to a report on NPR’s All Things Considered program, the Obama Administration has nominated Margaret Hamburg, MD to head the US Food and Drug Administration. Dr. Hamburg is a former health commissioner in New York City who has worked on issues surrounding infectious diseases and bioterrorism. In New York, she instituted a needle-exchange program to help prevent the spread of HIV. She also set up a program, in which health workers went to tuberculosis patients’ homes to help them manage their drug regimens.

A Harvard Med School graduate, Dr. Hamburg was an assistant secretary of health and human services during the Clinton administration and now works at the Nuclear Threat Initiative, which tries to cut the threat from nuclear, chemical, and biological weapons. She opposes abstinence-based sex education in public schools and has been a critic of the marketing practices of the pharmaceutical industry. Further, Dr. Hamburg is a leading advocate for changes in the nation’s public health policies and infrastructure, from local health departments to the highest levels of government. Finally, after eight years of mismanagement and poor leadership, the agency has somebody at the helm with intelligence, experience and is an advocate for change. 

Kudos to Team Obama!

Until next time...

Good Luck and Good Job Hunting (FDA is hiring)!!!!!

 

Pharma and Twitter

Twitter, the microblogging platform, is the current rage in social media. According to @Shwen, who writes the Med 2.0 Blog, it grew by 752% in 2008. Shwen is a social media enthusiast who is trying to convince the life sciences industry that Twitter and other social networks can be leveraged to improve drug development and deliver healthcare.

According to a recent post on Med. 2.0, there are currently three pharmaceutical companies that are actively using Twitter: Novartis (@novartis), Boehringer Ingelheim (@Boehringer) and Astra Zeneca (AstraZenecaUS). Also, it appears that Johnson and Johnson (@JNJcomm) launched an account last week. Tweets from @novartis and @Boehringer occur fairly regularly whereas AstraZenecaUS tweets are rare. Unlike YouTube, where pharmaceutical sponsors who create channels can regulate and control content, it is much more difficult to manage Twitter because tweets are in real time, uncensored (for the most part) and can be globally disseminated within seconds.

Despite these issues, Med 2.0’s Shwen muses “I can only imagine that more pharma companies are going to be jumping on board the Twitter-train sooner rather than later. How they use it to engage, on the other hand, is going to vary greatly from company to company. At the very least, I see companies setting up accounts as “listening posts”, but others may choose to engage, like @boehringer does in an informal manner. Whatever the case, Twitter is fast becoming the new dominant space for listening and/or engaging the life sciences community.”

Like Shwen, I believe that it a matter of time before pharma and biotech realize that they must embrace social media (in all of its various forms) to remain competitive in today’s increasingly interconnected marketplace.

For those of you who may be interested, you can follow BioJobBlog (@Biojobblog) and Biocrowd (@Biocrowd) on Twitter too!

Until next time…

Good Luck and Good Twittering

 

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Career Opportunities in Drug Development

Ever wonder how a drug makes it from the bench to the marketplace and what types of jobs are required to support the process? I created a PowerPoint presentation that describes the activities and the jobs required at each stage of the development process. I also listed the degree requirements that are necessary to secure various jobs from drug discovery through commercialization.

FDA Delays Approval of Ceftobiprole to treat MRSA

U.S. regulators have delayed a decision on approval of an antibiotic from Johnson & Johnson and Basilea saying they need further audits of clinical sites, the two companies said on Wednesday.

Ceftobiprole, a broad-based spectrum antibiotic targeted mainly against infections caused by methicillin-resistant Staphylococcus aureus (MRSA), is Basilea's lead product and the news hit the Swiss biotech shares, which plummeted 27 percent.

In a so-called complete response letter on the drug's approval application, for complicated skin and skin structure infections, the Food and Drug Administration (FDA) said it was unable to review the clinical data submitted with the NDA until issues of data integrity had been resolved. The FDA has asked J&J to conduct additional audit work of clinical investigator sites and to address specific questions related to site monitoring."

Ceftobiprole is approved in Canada and Switzerland and has been recommended for approval in the European Union. A new application in the United States is planned within a year.

Late last week, FDA rejected an NDA for another antibiotic, iclaprim, being developed by Arpida, another Swiss company. It has been a bad two weeks at FDA for approval of new antibiotics—drugs that we desperately need.

Until next time….

Happy Thanksgiving

 

Optimer's New Carbohydrate-Based Antibiotic May Be a Winner

Optimer, a San-Diego, CA-based biopharmaceutical company, reported positive Phase III clinical trial results for OPT-80, its lead treatment for Clostridium difficile gastroenteritis. C. difficile gastroenteritis is caused by exotoxins secreted by clostridia that have colonized the colon following prolonged antibiotic treatment for other bacterial infections. If left untreated, patients can die from a pseudo-membrane that forms in the colons of C. difficile-infected people. The incidence of C. difficile gastroenteritis has drastically increased over the past decade because of prolonged treatments with multiple antibiotics that are often necessary to eradicate infections caused by multiple drug resistant bacteria.

Historically, CHO-based drugs (with a few notably exceptions like heparin) have not fared well as therapeutic agents. To my knowledge, OPT-80 is the first synthetic carbohydrate (CHO)-based antibiotic to demonstrate anti-bacterial efficacy in a Phase III clinical trial. Having worked for Transcell Technologies (now defunct) and Alchemia,Pty—both of which attempted to develop CHO-based antibiotics—Optimer’s clinical success with OPT-80 is certainly noteworthy. I wish the company continued success in the future—mostly because I have always thought that carbohydrates would make good antibiotics!

 

Until next time…

 

Good Luck and Good Job Hunting!!!!!!

 

 

The End of an Era: Ligand Pharmaceuticals to Buy Pharmacopeia for $70 Million in a Stock Deal

New Jersey-based Pharmacopeia, the first-ever combinatorial chemistry company, announced that it had agreed to be purchased by Ligand Pharmaceuticals in a stock deal worth about $70 million. Onetime a leader in combinatorial chemistry and high throughput screening, Pharmacopeia has struggled of late after it jettisoned its profitable molecular modeling division several years ago. While the company was able to advance several of its lead compounds into early phase clinical testing, its  longtime business model, predicated on multiple, small discovery deals with large pharmaceutical companies, was unable to provide enough capital to continue to sustain operations.

Pharmacopeia was established in 1993 after its founders licensed from Columbia University several of the first issued combinatorial chemistry patents. The company was a pioneer in combinatorial chemistry (and subsequently high throughput screening) and was the first to publicly tout the virtues of combinatorial chemistry in drug discovery. By the mid-1990s, many pharmaceutical companies had embraced combinatorial chemistry as the “next big thing” and began eliminating traditional natural product and medicinal chemistry jobs. The industry’s love affair with combinatorial chemistry grew so strong that many companies (most notably Merck), completely eliminated their natural products discovery departments in the late 1990s. Unfortunately, the role of combinatorial chemistry in drug discovery never lived up to its promised potential and was largely abandoned in the early 2000s. Although combinatorial chemistry is now part of the modern day drug discovery paradigm, this onetime “shining star” has largely been relegated to a minor supporting role.

I first became acquainted with Pharmacopeia in 1994 after I took a job with Transcell Technologies, a now-defunct biotechnology company that was co-located with Pharmacopeia in a research facility in Monmouth Junction, NJ. While Transcell and Pharmacopeia shared a cafeteria and some common laboratory equipment, Pharmacopeia employees were strictly forbidden to talk with Transcell employees— lest they inadvertently divulge proprietary combinatorial chemistry concepts that might jeopardize the company’s future. Coincidentally, a guy who lived two doors down from my family and me turned out to be Pharmacopeia’s in-house intellectual property attorney. Although, Ron and I became good friends, he was also extremely tight-lipped about the “goings-on” at Pharmacopeia. Privately-held Pharmacopeia went public in 1995 and at one time, its market capitalization was almost $1.0 billion.

By any reckoning, a 15-year run is outstanding for a biopharmaceutical company. However, as the old adage goes, “All good things must come to an end.” At present, it is not clear, whether or not California-based Ligand will relocate the company or cut jobs. Nevertheless, Pharmacopeia’s impending demise sends a clear signal that the golden age of combinatorial chemistry has ended!

Until next time….

Good Luck and Good Job Hunting!!!

 

Japan's Daiichi Sankyo Co Buy's Generic Manufacturer Ranbaxy

Daiichi Sankyo will buy a controlling interest (50.1%) of Ranbaxy, India’s third largest generic manufacturer.  Daiichi will pay as much as $4.6 billion for the opportunity.

The deal will put Daiichi Sankyo into ninth place in the $120 billion generic-drug market behind leaders Teva Pharmaceutical Industries Ltd. and Novartis AG's Sandoz unit. According to the report “Daiichi Sankyo is mimicking strategies pursued by Novartis and Johnson & Johnson to weather turbulence in the branded-drug industry by diversifying into other markets. The acquisition also gives the Japanese company more reach in emerging regions including India, China and Eastern Europe. “

I think after this deal, that other pharmaceutical companies may consider buying profitable generics businesses. I am not sure why it has taken innovator companies so long to realize that it is much easier to join (buy??) rather than compete with generic manufacturers. It just seems so obvious to me—and I don’t even have an MBA!  Maybe there is some truth to the age-old aphorism “missing the forest for the trees.”

Until next time…

Good Luck and Good Job Hunting!!!!!

Novartis Buys US-Based Antibiotic Discovery Company

Novartis announced today that it intends to purchase Malvern, PA-based Protez Pharmaceuticals for $400 million. Protez is developing a novel spectrum carbapenem antibiotic that is active against variety drug-resistant Gram positive (most notably MRSA )and Gram negative bacterial pathogens. Its lead compound, PZ-601, is in Phase II human clinical testing. Protez acquired PZ-601 (formerly SMP-216601) in 2005 from Dainippon Sumitomo Pharmaceuticals.   

Novartis is buying Protez to sure up its antibacterial drug pipeline. Novartis already sells Cubicin, (manufactured by Massachusetts-based Cubist Pharmaceuticals Inc.,) in Europe and is developing other antimicrobials including Aurograb and Tifacogin to treat infections.

Like many of the newly marketed antibiotics, PZ-601 is injected and not orally bioavailable. Nevertheless, it is likely that PZ-601 will provide much needed help against the ever increasing number of drug resistant bacterial isolates. Swiss companies Basilea Pharmaceutica AG and Arpida Ltd. are also working on experimental medicines to treat MRSA.

It is not clear how the acquisition will affect Protez employees.  I suspect that most of the employees will keep their jobs except for Company officers.

Until next time…

Good Luck and Good Job Hunting!!!!!

A New Age is Dawning: FDA to Go On a Hiring Spree!

The Food and Drug Administration (FDA) announced today that it wants to hire 1,300 biologists, chemists, medical officers and others over the next several months. The agency currently employs more than 10,000 people and wants to add 600 new employees and backfill more than 700 that have been vacant by October. The new hires will triple the number hired from 2005 to 2007. Roughly 30% of all regular FDA staffers and approximately half of FDA managers are already eligible to retire.

An FDA spokesperson said that 400 of the new jobs will be related to drug application review and another 150 will be hired as inspectors to inspect drugs, foods and other related items. The agency will rely on user fees from drug companies to pay for all drug review jobs and about 100 other positions. The rest will come from the funds that were recently appropriated by Congress.

In addition to drug reviewers and inspectors, FDA is seeking consumer safety officers, nurse consultants, statisticians, epidemiologists, pharmacologists, pharmacists and veterinarians. Most of the positions are in the Washington D.C area but some are overseas and in other parts of the US.

This is one of the largest hiring initiatives in FDA’s history. It’s about time that Congress realized that the agency has been seriously under funded and understaffed ever since Bush was elected in 2001. I suspect that the impetus for the additional funding and hiring initiative has a lot to do with the beating that the agency has taken over the past few years. As we all know, FDA has been blasted by consumer advocates and lawmakers for lax oversight and inefficiency.

I can’t recall whether I said this before, but FDA is a great place “to be from”. Many of my colleagues who worked at FDA for three or more years are now highly paid regulatory consultants charging the companies that hire them about $3,000 to $5,000 per day. That said, as a bit of career advice; opportunity is knocking—don’t dither and wait too long before you apply.

Until next time….

Good Luck and Good Job Hunting (at FDA)!!!!!!!!!!

The Real Problem at FDA

I spent the entire morning reading various articles, blog posts and comments about what is wrong with the US Food and Drug Administration (FDA). Not surprisingly, phrases like “drug lag”, the large size and costs of clinical trials, political and corporate influence, reduced numbers of NME approvals etc appeared ad nauseum. These are the same old, tired complaints with the agency that have been bandied about for the past 10 years or so. 

In my opinion, the bottom line is this: the agency is egregiously under staffed and under funded despite the fact that companies pay steep user fees for regulatory reviews. I can understand why corporate America is dissatisfied with the service that it receives from FDA. It is natural to expect good customer service after paying large sums of money to a service provider.  However, it is important to note, that the words “customer service” don’t appear any where in the Food, Drug and Cosmetic Act of 1938 (although it can possibly be implied fromPDUFA in 1992 and FDAMA in 1997).  Nevertheless, what is mentioned in the FD&C is SAFE and EFFICACIOUS pharmaceuticals, biologics and medical devices. Put simply, safe and efficacious products, not customer service, is REAL the mission of FDA.  With this in mind, the agency is legally required to do everything in its power to provide Americans with carefully scrutinized and safe medical devices, pharmaceutical and biotechnology products.

If we Americans want FDA to accomplish its REAL mission, then the agency must be sufficiently funded, adequately staffed and have strong, non-partisan leadership. Unless this occurs, FDA will continue to struggle and remain dysfunctional well into the 21st century.

Until next time…

Good Luck and Good Job Hunting!!!!!

Drug Sales Dip...Oh My!!!!!

According to a press release by IMS, a company that tracks pharmaceutical sales, growth of the US pharmaceutical market shrank from 8% in 2006 to a meager 3.8% in 2007–the slowest growth rate since 1961. Total U.S. prescription sales in 2007 only reached $286.5 billion. The 2007 slowdown in sales was attributed to:

  • Loss of patent exclusivity for branded products
  • Fewer new drug approvals
  • Effect of Medicare Part D on annual growth
  • Renewed focus on safety issues by US Food and Drug Administration

Industry officials place the blame for the slow down on FDA because fewer newer drugs were approved in 2007 as compared with years past. However, I believe that the slow down has more to do with:

  • Higher prices of branded medications as compared with generic drugs
  • Lack of public confidence in the pharmaceutical industry
  • Increased scrutiny by regulators on direct to consumer advertising and continuing medical education (CME)
  • Fewer and less innovative drugs in company pipelines

Bashing FDA is easy. The willingness of the pharmaceutical industry to assume ownership of some of its own shortcomings and missteps is substantially more difficult to do!

Until next time….

Good Luck and Good Job Hunting!!!!!!!!

Eli Lilly & Co Vows to Fight US Legislation That Allows Importation of Lower-Priced Prescription Drugs

As the cost of prescription drugs continues to spiral upward, the affordability and accessibility to prescription drugs and healthcare will likely be fiercely debated and may influence the outcome of the presidential election next November. Despite growing public concern over the cost of prescription drugs in the US, Eli Lilly has vowed to fight federal legislation that will allow Americans to import lower-priced prescription drugs from Canada, Japan, Australia and many European nations. Lilly spokespeople and their lobbyists in Washington DC argue that the policy would put consumers at huge risk of consuming dangerous and unsafe counterfeit drugs. Big pharma has been using the drug safety argument for the past decade or so to stifle drug importation legislation. That said, blocking prescription drug importation legislation has very little to do with drug safety and everything to do with profit margins and corporate stock prices.

The stakes of prescription drug importation are high for drug makers. In contrast with the US, most other countries keep drug prices low through government distribution programs and strict price controls. Because the US government does not control prescription drug prices, American typically pay two-thirds more than Canadians, 80% more than Germans and 100 per cent more than French residents for identical prescription drugs. Lilly and other big pharma companies contend that price controls for prescription drugs stifle innovation and competition (tell that to the European and Japanese drug companies). Currently, according to government and industry surveillance data only a tiny fraction of counterfeit drugs (about 5 per cent) actually enter the US market. But Lilly and other pharmaceutical companies argue that there could be enormous increases in the number of counterfeit drugs that enter the US annually if Congress relaxes the federal ban on imported prescription drugs.

Pharma’s counterfeit drug argument is a convenient scare tactic that it has been using to lobby against relaxing current drug importation legislation. What the drug makers don’t tell you is that they routinely import and sell drugs in America that are manufactured in foreign production facilities. Further, many of drugs that are sold in Canada, Europe, Japan and Australia are manufactured in the same production facilities that supply drugs that are sold in the US. This begs the question —if drugs are manufactured in the same foreign production facilities and one lot is sold in the US and the other in Canada, would American consumers really be at a greater risk if they bought a Company’s drug in Canada or the US? The answer to the question is a resounding NO–unless you believe that the Canadian Regulatory Agency is less competent at monitoring and approving drugs than the US FDA The real story is this–.counterfeiters stand to make much more money selling bogus prescription drugs in the US than in other countries because there are no price controls in the US (which means much larger profit margins for the counterfeiters–duh!)

Let me propose a solution to the prescription drug counterfeiting that is plaguing and threatening the safety of American–reduce the price of American prescription drugs to prices that are consistent with prescription drug prices in the rest of the world. This would provide greater access of prescription drugs to all Americans and reduce the need for some Americans to purchase prescription drugs from dubious sources because they can’t afford to buy them at their local pharmacies. Further, price controls would certainly reduce the incidence of counterfeit drugs in American because counterfeiters would no longer be able to command high prices for their products which, in turn, would seriously cut into their profit margins.

Despite the logic and simplicity of my proposal, don’t expect there to be any changes in prescription drug importation policies any time soon! Profits not drug safety or open access to life-saving drugs is what drives big pharma-this is American after all!!!

Until next time….

Good Luck and Good Job Hunting (try Indiana) !!!!!!!!!

The Impact of Prescription Drugs on Rising Healthcare Costs

Health care spending in the United States grew 6.7 percent in 2006 to $2.1 trillion, or $7,026 per person. This represents a slight increase over the 6.5 percent rate in 2005 (which was the slowest growth since 1999). Health spending accounted for 16 percent of US gross domestic product in 2006, outpacing overall nominal GDP growth by 0.6 percent. However, total health care spending in the US is not the real story here.

The federal government reported that the new Medicare drug benefit called Part D, which was implemented in early 2006, contributed to an 18.7 percent increase in Medicare spending that year, the fastest rate of growth since 1981 and double the rise in 2005.  In 2006, Medicare spending rose to $401.3 billion, up from $338.0 billion a year earlier, according to the government’s annual health spending report.

The impact on funding sources that paid for prescription drug benefits varied. The public share of spending (federal and state)  increased from 28 percent in 2005 to 34 percent in 2006, while funding from private sources (insurers) fell from 72 percent to 66 percent.  The shift in funding was most dramatic for Medicare and Medicaid. Medicare’s share of total retail prescription drug spending surged from just 2 percent in 2005 to 18 percent in 2006, following Part D implementation. Meanwhile, Medicaid’s share fell from 19 percent to 9 percent.

At present, the US government cannot negotiate prescription drug pricing with drug companies that produce the medications–only drug distributors and third party insurers can do that! As the baby boomer retirement continues, the amount of government spending on prescriptions drugs will increase exponentially and ultimately cause healthcare costs in this country to explode. In my opinion there are two options: impose price controls on prescription drugs or provide all US citizens with a national healthcare system that allows the government to negotiate drug pricing directly with drug manufacturers. And for those of you who think national healthcare is a fantasy–over 60% of all healthcare claims in the US are currently handled and paid by Medicare–a federally finaced and run government healthcare system!  We are closer to a national health insurance program than you think!

Until next time...

Good Luck and Good Job Hunting!!!!!!

Why is the US Congress Doing FDA's Job?

The US Food and Drug Administration (FDA), like other federal agencies during the Bush administration, has been hobbled by a lack of leadership and an agency-wide feeling of ennui. What do you expect from a federal agency that didn't did not have a Director for 5 out of 8 years since 2001? At present, the agency is in disarray, grossly ineffective and under siege.

Over the past 5 years or so, numerous product recalls and safety issues with newly-approved drugs have caused many medical professionals and the American public to lose faith in FDA. This is clearly evident by a willingness of the US Congress to step in and assume many of the regulatory activities and legal responsibilities granted to the agency in the Food, Drug and Cosmetic Act of 1938. For example, the New York Times reported today  that a Congressional committee is investigating Merck and Schering-Plough for their handling of a critical clinical trial of Zetia, their blockbuster cholesterol-lowering drug. The House Committee on Energy and Commerce demanded more information about delays in the trial, which was completed in April 2006 but whose results have not yet been released. Independent scientists have viewed the results of this study as crucial because it is the first trial that would answer whether Zetia’s ability to lower cholesterol has real biological benefits for patients. The results might also help answer nagging questions about Zetia’s safety.  I ask: "Why are their still nagging safety questions about a blockbuster drug that has been on the market since 2002? "

FDA’s mission is to insure that all approved drugs and medical devices are safe and effective for Americans. Overall, from a historical perspective, I think that the agency has accomplished its mission and done an outstanding job. It is only recently that things have begun to become undone and spin out of control. I believe that the time has come for FDA to “step up to the plate”  to right itself and get back on track. Personally, I would rather have medical and regulatory experts rather than politicians reviewing medical and scientific data to determine whether a drug is safe and efficacious. FDA may be broken but the damage is not irreversible. With a little determination, hard work and competent leadership the agency ought to be able to regain its former reputation as a preeminent regulatory agency.

Until next time….

Good Luck and Good Job Hunting (they are looking for a few good men and women)

A Sea Change at FDA?

In an attempt to dispel the notion that it is “dysfunctional” and "lax in policing drugs once they are on the market", the US Food and Drug Administration (FDA) earlier this week launched MedWatch - The FDA Safety Information and Adverse Event Reporting Program. An integral part of the new program is The Drug Safety Newsletter a quarterly publication that provides information on the findings of selected postmarketing drug safety reviews from FDA's Center for Drug Evaluation and Research.

The newsletter also provides information on important emerging drug safety issues and recently approved new molecular entities. FDA hopes the newsletter will raise awareness of reported adverse events, and stimulate additional adverse event reporting by healthcare professionals. The first issue of the newsletter contains reviews of the following products (information in the brackets are the most serious side effects)


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Publication of this newsletter fulfills a commitment FDA made in its January 2007 response to the Institute of Medicine's (IOM) 2006 Report on The Future of Drug Safety - Promoting and Protecting the Health of the Public.

The newsletter is available at The FDA website.  Also, it will be sent electronically to those who subscribe to the Drug Safety Newsletter or to the MedWatch E-list.

To subscribe to this publication directly, go to the Drug Safety Newsletter section of the FDA site, enter your name and e-mail address in the appropriate fields, and select the "Join the List" button.  Hopefully, this new publication will inform consumers about the potential adverse effects and side effects of marketed prescription medications.

Until next time.....

Good Luck and Good Job Hunting!!!!!!!!!!!

FDA Jobs?

In the January 2007 issue of Drug Discovery & Development, Ted Agres authored an informative article called "FDA's Sweeping Changes" that outlined reforms that are slated to occur at the agency. One of these is an amendment to the Prescription Drug User Fee Act (PDUFA; which is up for renewal) to increase user fees for regulatory reviews. For those of you who are not familiar with PDUFA, it was passed in 1992 and it authorized FDA to collect fees from industry to hire additional staff to meet faster approval goals for Investigational New Drug (IND), New Drug (NDA) and Biological License Applications (BLA). Under PDUFA, user fees have grown from $9 million or 7% of FDA's drug review costs in FY1993 to ca. $ $280 million or more than 59% in FY 2007 which began on Oct. 1, 2007.  

In addition to being used to speed drug review, the new fees will support post-market surveillance and post-market evaluation of drug safety. Further, for the first time, drug manufacturerers have agreed to provide user fees to support FDA review of direct to consumer advertising (DTC). At present, FDA has no authority over DTC ads prior to drug launch; companies submit copies of broadcast and print ads when they begin running. FDA is seeking the authority to review DTC ads before they can be aired or printed.

Increases in user fees suggest that the agency ought to be looking for a few "good women and men" to review regulatory submissions and institute its new focus on drug safety and surveillance.

Until next time......

Good Luck and Good Job Hunting!!!!!!!