January 19, 2012

Mobile Outreach Strategies for Screening Hepatitis and HIV in High-Risk Populations

Public Health Nurs. 2012 Jan;29(1):27-35. doi: 10.1111/j.1525-1446.2011.00970.x. Epub 2011 Oct 3.

Zucker DM, Choi J, Gallagher ER.


School of Nursing, University of Massachusetts Amherst, Amherst, MassachusettsMassachusetts General Hospital, Boston, Massachusetts.


ABSTRACT Objectives: To screen, counsel and offer hepatitis A and B vaccination for subjects at high risk for hepatitis C virus (HCV) and HIV, and determine any relationship between risk factors and HCV positivity. Design and Sample: A descriptive correlational design. We correlated risk factors and HCV positivity and measured vaccination completion rates. Two hundred and two unduplicated subjects in 4 locations in Western Massachusetts: a walk in substance abuse clinic, a homeless shelter, a county jail, and a community corrections facility. Measures: Demographic data and a standard HCV risk- screening survey were used. Results: Significantly higher rates of HCV were found in subjects who were currently using injection drugs (83.3% HCV positive, χ(2) (1)=20.85, p<.001), who had a history of sharing needles for drug use (75% HCV positive χ(2) (1)=83.20, p<.001), or a history of receiving treatment for drug abuse/alcoholism (38.4% HCV positive χ(2) (1)=12.14, p<.001). Vaccination completion ranged by setting between 18% and 38%. Conclusions: Targeted outreach to hard to reach groups is effective in providing access for those at high risk for HIV and HCV infection. A mobile outreach strategy can focus needed resources for a variety of groups in a community.

© 2011 Wiley Periodicals, Inc.


Combination of oral drugs suppresses common type of hepatitis C

Public release date: 18-Jan-2012

Contact: Mary F. Masson
University of Michigan Health System

Researchers targeted the type of hepatitis C most common in the United States, results reported in New England Journal of Medicine

Ann Arbor, Mich. – A new combination of investigational drugs successfully suppressed hepatitis C genotype 1 infection in a high percent of patients who had not responded to previous treatment in a study led by a University of Michigan hepatologist.

The study, which will be published Jan. 19 in the New England Journal of Medicine, focused on hepatitis C genotype 1, which is predominant in the United States and the most difficult to treat. Hepatitis C is a virus that infects the liver and can cause liver cancer and liver cirrhosis. It is transmitted through direct contact with infected blood and blood products.

In this pilot study, patients with hepatitis C genotype 1 infection, who had not responded to previous treatment with PEG-interferon alfa and ribavirin, were given a combination of two investigational direct-acting antiviral agents (daclatasvir and asunaprevir) alone, or were given these two antiviral agents along with PEG-interferon alfa-2a and ribavirin. All the patients saw their hepatitis C viral load drop rapidly, says Anna S. Lok, M.D., professor of Internal Medicine, Division of Gastroenterology at the University of Michigan Medical School and lead author of the study.

All 10 patients given the four drug treatment -- two direct-acting antiviral agents (daclastasvir and asunaprevir) that block the NS3 and NS5A regions of the hepatitis C virus plus PEG-interferon alfa and ribavirin -- had sustained virologic response with undetectable virus at the end of treatment and at 12 weeks after stopping treatment. Four of the 11 patients given the two direct-acting antiviral agents only also achieved sustained virologic response.

A sustained virologic response or SVR means there is no detectable Hepatitis C virus in a patient's blood after treatment is stopped. Achieving sustained virologic response is important, because research has shown that late relapse is rare.

"The two recently approved hepatitis C drugs – telaprevir or boceprevir -- combined with PEG-interferon alfa and ribavirin have limited success in patients who have not responded to previous treatment with PEG-interferon alfa and ribavirin. Because of this high unmet medical need, there is a necessity for new combination regimens that can increase response rates in that population," says Lok, who also is Director of Clinical Hepatology at U-M. "The high rate of sustained virologic response in patients who received the four drug regimen is very exciting. Although only four of 11 patients given the two direct-acting antiviral agents only achieved sustained virologic response, this is the first study to show that sustained virologic response can be achieved without the use of interferon or ribavirin. These data are very encouraging because PEG-interferon alfaand ribavirin are associated with many side effects and many patients with hepatitis C choose not to receive treatment for fear that they cannot tolerate those drugs."

An estimated 170 million people worldwide are infected with hepatitis C, with genotype 1 being the most prevalent genotype. Up to 80 percent of those infected with hepatitis C will become chronically infected. Twenty percent of people with chronic hepatitis C will develop cirrhosis and, of those, up to 25 percent may progress to liver cancer. Although there is no vaccine to prevent hepatitis C, it is a potentially curable disease.

In the Phase II clinical trial, Lok, along with a team of researchers including scientists from Bristol-Myers Squibb, studied patients with Hepatitis C genotype 1, who had not responded to prior therapy with PEG-interferon alfa and ribavirin. The study was funded by Bristol-Myers Squibb.

"Overall, these results suggest that further research into combinations of direct-acting antiviral agents, with or without PEG-interferon and ribavirin, should be encouraged," Lok says. "Caution must be exercised in selecting the right combination of direct-acting antiviral agents in studies of interferon-free regimens because in this study, all 7 patients who received only two direct-acting antiviral agents that did not achieve sustained virologic response had emergence of drug resistance variants to both drugs."

In this study there were no serious adverse events on treatment or discontinuations due to adverse events. Diarrhea was the most common adverse event in both groups, but it was mild or moderate in all cases.


Journal citation: N Engl J Med 2012;366:216-24

Funding: Bristol Myers Squibb.

Additional authors: David F. Gardiner, M.D., Kurt Zhu, Ph.D., Dessislava I. Dimitrova, M.D., Timothy Eley, Ph.D., Dennis M. Grasela, Pharm.D., Ph.D., Claudio Pasquinelli, M.D., Ph.D., Fiona McPhee, Ph.D., Tong Guo, Ph.D., Megan Wind-Rotolo, Ph.D., Anna Persson, Ph.D., all of Bristol Myers Squibb; Eric Lawitz, M.D., of Alamo Medical Research, San Antonio, Texas; Claudia Martorell, M.D., of The Research Institute, Springfield, Mass.; Gregory T. Everson, M.D., of the University of Colorado-Denver; Reem Ghalib, M.D., of the Texas Clinical Research Institute; Robert Reindollar, M.D., of the Carolinas Center for Liver Disease; and Vinod Rustgi, M.D., of Metropolitan Research, Fairfax, Va.

About U-M's Division of Gastroenterology: U-M is one of the largest gastroenterology practices in the country and is a leader in the prevention, diagnosis, and treatment of diseases of the gastrointestinal tract and liver. Our 50-plus physicians are experts in the diagnosis and treatment of all diseases of the gastrointestinal system, from simple to complex, including those of the esophagus, stomach, small intestine, colon, rectum, liver, gallbladder, pancreas and biliary tract.


Also See:

  1. First Hepatitis C Treatment Data Demonstrating Proof of Principle with Direct-Acting Antiviral-only Therapy Published
  2. Hepatitis C treatment with antivirals is effective: study
  3. Bristol-Myers Hepatitis C Pills Clear Virus Without Interferon
  4. New Combo KOs HCV Without Interferon, Ribavirin

Achillion's Hep C Pipeline Likely Can't Compete

By Adam Gefvert, Contributor

Thursday, 19 January 2012 08:16

Hepatitus C drug developers have been drinking champagne and eating caviar lately. Companies in this space that have shown little to no revenues for years have been getting acquired at huge premiums to their share price and for billions of dollars.

Pharmasset (VRUS) was offered $11 billion by Gilead Pharmaceuticals (GILD) in November 2011, for an over 100% premium to the share price. Gilead bought it for its PSI-7797 anti-HCV (Hepatitis C Virus) nucleoside. Bristol-Meyers Squibb (BMY) made a tender offer for Inhibitex over the January 7th weekend for $2.5 billion, a 160% premium over its share price. Also for its anti-HCV nucleoside.

With the recent heavy M&A action in the Hepatitis C space, drug development company stocks that are focusing on Hepatitis C drugs have taken off. Since the Inhibitex buyout on Jan 9, Achillion (ACHN) has gone from $7.92 to $12.95, for a 64% gain. It has since settled down to about $11.

However, Inhibitex and Pharmasset HCV drugs: INX-189, and PSI-7977, respectively, are nucleosides which are a different type of anti-viral drug than those currently used to fight HCV. Nucleosides are believed to be the next generation drug to fight HCV because they have shown in clinical trials to be able to destroy the HCV virus on their own without the aid of other drugs.

Achillion is at a disadvantage to its competitors because none of its HPV drugs in development are nucleosides.

The type of drugs currently used to fight HCV are protease inhibitors which are not able to fight the HCV alone. HCV’s mutations are able to resist protease inhibitors, so they must be used along with the standard of care treatment of pegylated interferon and ribavirin (PR) in order to cure patients. Use of a protease inhibitor along with PR gives a 75% chance to cure HCV, while treatment of only PR, the old method of fighting HCV, gives only a 50% chance to cure it.

The problem is, the side effects of interferon are so bad, that many patients would rather have the disease or wait for a better solution than deal with the treatment. Many patients say the side effects are worse than the disease itself.

The fact that big pharmaceutical companies paid so high a price for Pharmasset and Inhibitex nucleosides is a testament to the thesis that the future of HCV treatment is going to be done without interferon.

“We believe the interferon free era will come late 2015 and early 2016 and we would anticipate, from a time perspective, being competitive with that," said Inhibitex's chief executive Russell Plumb.

In the following picture, Pharmasset illustrates the contrast between the present and future of Hepatitis C treatment.


Achillion’s most advanced HPV drug that is currently going through phase II trials, is ACH-1625, which is a protease inhibitor. It has been going through preclinical trials since 2008 before it was discovered that nucleosides can efficiently fight the HCV. If ACH-1625 won’t work without the help of interferon, then it will pretty much be worthless. By the time it gets to market in 2015 or 2016, if it gets approved, there won’t be any HCV patients willing to do a treatment with interferon.

There is a glimmer of hope for protease inhibitors though. In October 2011, Abbott Laboratories and partner Enanta Pharmaceuticals announced positive results from a phase 2 study of ABT-450, their oral protease inhibitor against HCV, without the use of interferon.

“In the trials, 44 previously untreated patients with hepatitis C were given ritonavir with Abbott's ABT-450 and one of two Abbott polymerase inhibitors, ABT-333 or ABT-072, and ribavirin for 12 weeks. All patients who remained in the studies achieved an early virologic response at 12 weeks, and of the 10 patients to date who were tested 24 weeks after completing the treatment course, nine had achieved a sustained virologic response”, the company said.

Abbott said it could have this shorter duration combination therapy for hepatitis C on the market in 2015 with annual sales potential of about $2 billion.

Early virologic response is a reduction of 2 or greater log in HCV RNA (hepatitis C ribonucleic acid) at week 12 of therapy, and this predicts sustained virologic response, which is an undetectable level of HCV RNA, at further treatments.

"We are seeing there is another way of achieving a regimen without interferon that looks like it will be competitive, it will eventually all boil down to who has the better data,” said Leerink Swann analyst Howard Liang.

However, Brean Murray Carret & Co. analyst Brian Skorney noted that "I continue to believe Pharmasset's [therapy] will be better." (FYI - this was stated before Gilead made the offer to acquire Pharmasset).

Merck is also working on an interferon-free regimen with their protease inhibitor MK-5172. From the company website: “MK-5172 suppressed HCV in patients infected with HCV genotypes 1 and 3. In addition, new in vitro data shows antiviral activity against a wide range of resistant mutant HCV types. The company is actively pursuing the use of MK-5172 in an interferon-free regimen for HCV.”

Achillion’s ACH-1625 drug hasn’t been proven to work without the help of PR. The drug has quite a few obstacles to climb to be worth anything. It would not only have to show effectiveness against HCV without interferon, but it would also have to compete with the nucleosides’ data when they come to market, as well as Abbott’s ABT-450 if it becomes successful, and Merck’s protease inhibitor and those of other big pharma companies. Then there’s all the resources and expenses necessary to get it through the trials. Phase III trials alone would likely cost over $100 million.

Besides ACH-1625, all its other drugs in the pipeline are in the preclinical stage or are starting phase 1 trials. It wouldn’t make any sense for a big pharmaceutical company to acquire Achillion at its current elevated price. Most of them are already working on their own HCV drugs. For example, Vertex and Alios BioPharma have teamed up to do clinical trials of their nucleoside drugs ALS-2200 and ALS-2158.

As shown in the Q3 2011 report, Gilead Sciences had entered into a research collaboration and license agreement with Achillion in 2004, and is continuing to do a minimal amount of collaborative research with the company, only paying $64K last quarter. Then Gilead went ahead and acquired Pharmasset for $11 billion totally snubbing Achillion. If any big pharma was going to buy Achillion, it would seem that Gilead would’ve been a good candidate since they have worked together for awhile. Achillion’s market cap was only about $400 million in late November when Gilead bought Pharmasset.

It’s unlikely that Achillion will be able to find an interferon-free treatment for HPV with ACH-1625 because when the drug was first designed, it didn’t have that goal in mind. Now, going through its phase 2 trials, with all the competition, I’m giving it a 15% chance that it will be able to develop an interferon-free regimen and become a top HPV drug with $2 billion a year in revenues like Abbott predicts its ABT-450 drug will peak at.

Achillion’s other two HCV inhibitors, ACH-2684 and ACH-2928, are going through phase 1 trials, so I’m giving them a 10% chance to succeed and reach the $2 billion annual sales number. I’m not including in the value calculation Achillion’s drugs still going through preclinical trials.

Even if Achillion managed to develop and commercialize a $2 billion a year in sales drug, it would need help to market it as it doesn’t have any experience selling drugs. That’s why the company is looking for an acquirer, or a big pharma to continue with the trials from here, take on the expenses, and give Achillion royalty payments once the drug hits the market. The latter is the scenario I use in my discounted cash flows analysis.

Continue Reading …

New Combo KOs HCV Without Interferon, Ribavirin

By Michael Smith, North American Correspondent, MedPage Today
Published: January 18, 2012
Reviewed by Dori F. Zaleznik, MD; Associate Clinical Professor of Medicine, Harvard Medical School, Boston.

A combination of direct-acting antiviral agents aimed at hepatitis C -- and given without standard therapy -- can lead to sustained virologic response in patients with a difficult-to-treat strain of the virus.

In an "exploratory" phase II study, four of 11 patients treated with the two agents daclatasvir and asunaprevir had undetectable levels of the virus 12 and 24 weeks after the end of treatment, according to Anna Lok, MD, of the University of Michigan Ann Arbor, and colleagues.

All of the patients had previously failed standard therapy with pegylated interferon and ribavirin, Lok and colleagues reported in the Jan. 19 issue of the New England Journal of Medicine.

The finding is a "proof-of-concept" that combining agents that directly target the virus through different mechanisms can yield good outcomes even without the standard therapy, the researchers argued.

On the other hand, results were even better in the second arm of the study, in which 10 patients were given all four drugs: all had a sustained virologic response 12 weeks after stopping treatment and nine still had undetectable levels of hepatitis C RNA after 24 weeks.

Sustained virologic response – defined as a plasma level of viral RNA of less than 10 IU per milliliter 12 weeks after treatment ends – is regarded as the functional equivalent of a cure, since the virus rarely rebounds after that.

In clinical trials, standard therapy with pegylated interferon and ribavirin yields sustained virologic responses in no more than half of patients with the difficult to treat genotype 1 and in no more than 80% of those with genotypes 2 or 3.

Adding either of the approved direct-acting agents – telaprevir (Incivek) and boceprevir (Victrelis) – improves those outcomes markedly.

But regimens including pegylated interferon and ribavirin are difficult to take and real-world effectiveness is much lower, leading to a growing interest in other agents that attack viral replication directly and may be used without interferon and ribavirin.

That's why the current study is a "watershed moment" in hepatitis C therapy, according to Raymond Chung, MD, of Massachusetts General Hospital in Boston.

In an accompanying editorial, Chung said that researchers can "certainly" do even better than Lok and colleagues by adding other direct-acting agents into the mix.

With other classes in development – such as nucleotide polymerase inhibitors – "we are on the threshold of a treatment revolution," Chung argued.

"There has never been a more exciting time for patients and providers who grapple with this silent killer," he concluded.

The two drugs under study both attack the viruses' ability to replicate inside cells. Daclatasvir inhibits the NS5A replication complex, while asunaprevir blocks the activity of the NS3 protease enzyme.

For this study, Lok and colleagues enrolled 21 patients with genotype one hepatitis C who had not responded to previous therapy and assigned them randomly to get the two drugs alone or in combination with standard therapy for 24 weeks.

The primary endpoint was a sustained virologic response 12 weeks after therapy ended.

Lok and colleagues reported:

  • Four patients in the two-drug group (36%) met the primary endpoint, including two of the nine with viral genotype 1a and both of those with genotype 1b.
  • Six patients -- all with genotype 1a -- had viral breakthrough while receiving therapy, and in all of them the researchers found resistance mutations to both antiviral agents.
  • All 10 patients in the four-drug group had a sustained virologic response 12 weeks after treatment, and nine maintained that for another 12 weeks.

The most common adverse event in both groups was diarrhea, and six patients had transient elevations of alanine aminotransferase levels to more than three times the upper limit of the normal range.

The study is not the first to find such a result; Japanese researchers have also shown that the two drugs in combination – but without interferon -- can lead to promising outcomes.

But in that open-label, single-arm study, all the patients had genotype 1b virus, which appears to respond better to therapy than genotype 1a.

The study was supported by Bristol-Myers Squibb.

Lok reported financial links with Abbott, Bristol-Myers Squibb, Gilead Sciences, GlaxoSmithKline, Merck–Schering-Plough, and Roche. Other authors also reported financial links with industry and several are either employees of or hold stock in Bristol-Myers Squibb.

Chung reported financial links with Merck, Gilead, Pfizer, Roche, and Schering.

Primary source: New England Journal of Medicine
Source reference:
Lok AS, et al "Preliminary study of two antiviral agents for hepatitis C genotype 1" N Engl J Med 2012; 366: 216-224.

Additional source: New England Journal of Medicine
Source reference:
Chung RT "A watershed moment in the treatment of hepatitis C" N Engl J Med 2012; 366: 273-275.


Also See:

  1. First Hepatitis C Treatment Data Demonstrating Proof of Principle with Direct-Acting Antiviral-only Therapy Published
  2. Hepatitis C treatment with antivirals is effective: study
  3. Bristol-Myers Hepatitis C Pills Clear Virus Without Interferon

Where Drug Names Come From


Naming Convention Drugmakers propose generic names for new drugs by starting with stems that describe structure, function, and targets, then tacking on syllables of their choice.

Chemical & Engineering News Volume 90 Issue 3 | January 16, 2012 | pp. 36-37

Behind every generic name lies a specific process

By Carmen Drahl

It isn’t every day that a molecular moniker is on the docket at Illinois’ Cook County Circuit Court. But then, the 2002 case of cis-8-methyl-N-vanillyl-6-nonenamide was most unusual.

The trouble wasn’t with the compound’s International Union of Pure & Applied Chemistry-approved name. It was that cis-8-methyl-N-vanillyl-6-nonenamide also happens to be a medication. Drug molecules get an additional, simpler name called a nonproprietary name or generic name. Winston Pharmaceuticals, a company that develops products based on cis-8-methyl-N-vanillyl-6-nonenamide, sought to change that molecule’s generic name, which an independent body had chosen in-line with decades of drug-naming conventions. If the case went Winston’s way, more than a name on a box would have been at stake.

Drug naming rarely involves drama. But this example illuminates a little-talked-about layer in drug development, one that affects doctors, pharmacists, and patients.

Unlike IUPAC-sanctioned chemical names, generic names usually describe a drug’s physiological function rather than its chemical structure. Today’s regimented generic-naming process got its start in the 1960s, a time when drugs had grown complex in structure and IUPAC names had grown to unwieldy lengths. In 1961, the American Medical Association, the U.S. Pharmacopeial Convention, and the American Pharmacists Association created the U.S. Adopted Names (USAN) Council to select concise generic names. The Food & Drug Administration joined the effort in 1967.

Today, the USAN Council names the active ingredients in drugs, biologics, vaccines, and even contact lenses and sunscreens. The council recommends names to the World Health Organization’s (WHO) International Nonproprietary Names (INN) program, which ultimately chooses a single name for each new drug that’s acceptable worldwide. For drugmakers, obtaining a generic name is a required part of bringing new products to market. Choosing a brand, or trade, name is an entirely separate process.

USAN Council members believe it’s important to develop drug names that are free for anyone to use, says Ruta Freimanis, who served as associate executive secretary and then as executive secretary of the USAN Council between 1978 and 2000. Brand names might be handy at first, “but eventually drugs do go off patent,” she says. A generic name “can go in the literature, on package labels, or even in educational materials” without copyright issues related to brand names, she explains.

The naming process itself “is an evolving type of science,” says Stephanie C. Shubat, the current director and secretary to the USAN Council. Generic names have evolved from being truncated versions of chemical terminology to being largely independent of it, she explains.

A list of naming rules, some of them quirky, has evolved as well. The letters h, j, k, and w are off-limits because they lead to pronunciation problems in other languages. Drugmakers can suggest names to the USAN Council, but any name with an implication that a drug is better, newer, or more effective than the competition heads straight for the reject pile, Shubat says. When a prospective name reaches the WHO stage, international connotations come into play. A name that sounds perfectly fine in English might have bad or even obscene connotations elsewhere. No one wants to sell the Chevy Nova of the drug world.

The crux of the generic-naming system is a collection of short name fragments called stems. Each stem has a meaning connected to a particular drug class or mode of action. The official list of USAN and INN stems and substems has grown and changed over time as companies come up with new classes of drugs, Shubat explains.

Understanding drug names through stems is a lot like learning English vocabulary by studying Greek and Latin roots. Learn what the stems mean, and you’re most of the way to figuring out what a drug does. Take top-selling drug Nexium, which has a generic name of esomeprazole. The stem in that name is -prazole, which means the drug is a benzimidazole antiulcer agent. The drug’s es- prefix describes the nature of the drug’s chirality—esomeprazole is dextrorotatory and contains a chiral center in the S configuration.

A prefix, in fact, was a player in the Winston case. The generic name Winston wanted to change, zucapsaicin, contains the prefix “zu,” which comes from German chemical nomenclature and indicates a cis isomer. Zucapsaicin is the cis isomer of capsaicin, a compound in chili peppers. The molecule targets a specific ion channel and can be used to treat pain, inflammation, or itch, says Joel E. Bernstein, a physician and Winston’s chief executive officer. Winston requested a name change from zucapsaicin to civamide, which according to the company was commonly used in hospitals and pharmacies.

It’s possible to change generic names, but only on rare occasions, and usually only for safety reasons. In 2009, for instance, the entire family of botulinum toxin drugs, which includes the popular cosmetic Botox, got a generic-name makeover in light of reports of serious side effects and deaths from dosage mix-ups.

Winston did not win its court case. A 2004 petition to FDA to change the name didn’t work out either. The name zucapsaicin was found to be in-line with established naming precedents. As for name confusion among physicians and pharmacists, the USAN Council concluded Winston was partly to blame.

The name zucapsaicin had been on the books since 1994. The council negotiated the name with a company called GenDerm, which owned the rights to the drug at the time. Civamide was a generic name GenDerm suggested. After that name was rejected, GenDerm continued to use the name civamide in the literature and its documentation. Winston continued the practice when it acquired the rights to the drug in 1999.

Most of the documents Winston cited to support its claim are dated after 1994, wrote then-USAN program director Sophia V. Fuerst in a letter to Winston. It’s both Winston and GenDerm’s “use of the name civamide after the name zucapsaicin was adopted that has caused the confusion,” she wrote.

Bernstein disputes that idea. Still, he says, “we weren’t able to get USAN to change their mind, nor FDA, so we have zucapsaicin.”

Most of the time, a simple back-and-forth between a company and the USAN Council is enough to settle any name disputes, says John E. Kasik, professor emeritus at the University of Iowa Carver College of Medicine and a longtime member of USAN’s review board, which settles naming spats. In fact, the review board has only had to step in to resolve five disputes throughout its decades-long existence.

Sometimes small disagreements occur when a manufacturer asks for a new stem to be created, Shubat says. It’s the council’s job to keep naming as streamlined as possible, which means being conservative when it comes to adding new stems, she explains.

“Manufacturers have to supply concrete arguments as to what differentiates their compound to qualify for a new stem,” Freimanis says. Drugs within the same category are different, she says, “otherwise manufacturers wouldn’t be selling them.”

Once the council builds in stems, prefixes, and other conventions, “a lot of times a name is three-quarters predetermined,” Shubat says. Once in a while, though, companies get to do something special with the syllable or two they supply. Onyx Pharmaceuticals’ experimental multiple myeloma treatment carfilzomib is named after molecular biologist Philip Whitcome and his wife, Carla, who both succumbed to cancer. (The ph in Philip was changed to an f to make the name compatible with multiple languages.) Philip Whitcome was a founder of the company Proteolix, which first developed carfilzomib, says Onyx spokeswoman Lori Melançon. With the name, the company “wanted to celebrate both Phil and Carla’s legacy,” she says.

Bristol-Myers Squibb’s experimental hepatitis C drug asunaprevir gets part of its name from Li-Qiang Sun, the chemist who first made it, says Joel C. Barrish, BMS’s vice president of medicinal chemistry.

And dasatinib, a chronic myelogenous leukemia medication BMS markets under the brand name Sprycel, is named for research fellow Jagabandhu Das. Das, or Jag, as he’s known around the labs, didn’t discover dasatinib. “What Jag did was challenge dogma,” Barrish explains. On two separate occasions, Das’s discoveries pulled his teammates out of medicinal chemistry ruts.

Long after a drug’s patent expires, “it’s the generic name that will always be remembered,” Barrish says. “Being able to recognize Jag that way for his accomplishments made the whole team feel good.”

Chemical & Engineering News

ISSN 0009-2347
Copyright © 2012 American Chemical Society


A Glucose Meter That Detects Viruses


Virus Meter? By making glucose a signal for viral DNA, researchers repurposed a glucose meter into a virus detector. Credit: Shutterstock

January 18, 2012

Medical Diagnostics: Researchers convert device for monitoring diabetes into one that can spot hepatitis B

By Erika Gebel

Although scientists have developed a variety of cheap, portable instruments for doctors to use in the field to pinpoint viruses, none have hit the market. To speed things along, researchers have now converted a commercially available device—a glucose meter—into one that can spot viral DNA (Anal. Chem., DOI: 10.1021/ac203014s).

“Our idea was to start with a technology that is already mature,” says Yi Lu of the University of Illinois, Urbana-Champaign. He and his team repurposed glucose meters, which people with diabetes commonly use to monitor their blood sugar, into virus meters by using glucose as a proxy for viral DNA. The scientists designed a chain of biomolecular interactions to link the two.

With hepatitis B as the virus they chose to detect, they first made two DNA probes that each would recognize half of the virus’s DNA sequence. The researchers then attached one probe to a tiny magnetic bead and the other to invertase, an enzyme that turns sucrose into glucose.

They tested their system by adding both probes to a solution of hepatitis B DNA at a known concentration. As the mixture incubated for a couple of hours, each strand of viral DNA bound both probes, thereby linking the enzymes to the beads. The researchers then isolated the beads with a magnet and placed them in a sucrose solution, where the enzymes slowly produced glucose. After three hours, the scientists removed the beads and measured the solution’s glucose concentration with a glucose meter.

Based on the measurement, they could determine how much invertase was present and, in turn, the amount of viral DNA in the original solution. Their system could detect hepatitis B DNA down to 40 pM, a level adequate to diagnose the disease at some stages, but not all. To improve the method’s sensitivity, Lu wants to increase incubation times and possibly engineer an enzyme that produces more glucose.

Chemical & Engineering News
ISSN 0009-2347
Copyright © 2012 American Chemical Society