So lately I’ve been helping to take care of a dog that has proven to be a remarkable, and damned near heartbreaking, challenge. (Well, considering we all live indoors and have plumbing and electricity and stuff. I don’t want to get too high-flown here. A Jack London story this ain’t.)
Ellie is a 12- or 13-year-old Australian Cattle Dog mix, weighing in at about 60 pounds. (An alternative name for this breed is “Blue heeler.”) I first became acquainted with her toward the end of last year. A friend of mine does a lot of house-sitting and pet-sitting, and I often lurk nearby when she does; Ellie’s family is a frequent client. My initial meetings with Ellie were on the turf of her owner Jil’s parents, who live less than a mile from Jil and her husband and own a similarly aged, better sighted, more arthritic pooch named Mollie. Mollie’s owners are also frequent clients of my friend the sitter. When Jil is out of town, Ellie usually stays at Mollie’s, and when Jil and her parents are both out of town (which happens more often that you might think, not that I’m reading your mind), the dogs and my friend all stay at Mollie’s. Which is a hell of a nice house, since you asked.
I will never fathom how marketing comes up with brand names for Rx drugs. Anyway, the FDA officially approved telaprevir (see post below) on Monday, May 23.
From Zennie62’s blog on SFGates (San Francisco Chronicle), here’s an interview with Steve Goodwin, a chief engineer who was diagnosed with hepatitis C, who was treated with telaprevir/Incivek. In the video, Goodwin tells “how he came to find out about Incivek via the use of the website Clinical Trials, at clinicaltrials.gov, and how it’s helped him to a more normal path of life.”
This week, panels of non-FDA experts reviewed the clinical data for Merck’s* boceprevir and Vertex’s telaprevir for potential market approval as first-in-class** treatments for patients infected with hepatitis C.
Are telaprevir and boceprevir perfect drugs? No. Each has side effects. There are the proven side effects of Xarelto even. I’ll note, however, that the “nasty rash,” the most common adverse effect (AE) of telaprevir, was generally mild to moderate and treatable with antihistamines or corticosteroid creams. Only 2% of subjects discontinued treatment because of the rash. So it’s an AE that is tolerable.
The drugs will also be quite expensive: $35-40K per course of treatment. Yikes almighty! Yet these are complex molecules that are not facile to synthesize. Also, consider that a liver transplant costs in the order of $250K to $310K (and higher).
That’s the structure of “my baby” above. Of course, it’s not strictly mine. Not by a long shot, but with all the work I did on that molecule, I feel like one of its many parents. We had a hell of a team at Vertex, and there’s a critical piece of the molecule that was added by Mark T., a wicked smart medicinal chemist, who was then at Lilly (former collaborators; Lilly and Vertex had, uh, differences in approach and thus had a fairly amicable divorce). My contribution was to study the detailed inhibition kinetics of VX-950, using isolated HCV protease for in vitro assays. I demonstrated that VX-950 was a slow binding inhibitor with a slow off-rate. It’s sticky in other words, and hangs onto the the protease for a good while before being hydrolyzed off the enzyme by water in the cell.
The close teamwork of biochemists/enzymologists and virologists at Vertex proved to be a very powerful combination. The virology team was able to demonstrate the efficacy of the protease inhibition in their viral RNA replication assay, and that the slow off-rate appears to play a role. These experiments were performed in 2003/2004, and became pivotal elements of the package, which included major contributions from medicinal chemistry, protein chemistry, process chemistry, toxicology, and pharmacokinetics, which brought VX-950 (telaprevir) forward as a clinical candidate. And now…well, I wonder what its brand name will be?
The odds of a compound at the bench becoming a drug are incredibly small, e.g., for every 10,000 compounds that enter the drug discovery pipeline, only 250 will progress to pre-clinical development (2.5-5%); 5 move forward into human testing, Phase I studies (0.1-0.5%); and only a single compound will survive through Phase II and Phase III studies to be an approved drug (0.01%).
So this is a rare thing, and telaprevir is not just any drug. It will meet a significant unmet medical need. Anyway, forgive me for so much gratuitous backslapping, but I’m proud to have been part of the team — a great group of scientists, many of whom (including myself) no longer work at Vertex — who discovered the compound and brought it to clinical candidate status.
*Boceprevir is actually from the former Schering-Plough, which Merck acquired.
** Strictly speaking, boceprevir is the first approved HCV protease inhibitor and thus truly “first-in-class,” but I use the phrase collectively here, as the approvals were almost back-to-back.
Hello there. Doc Bushwell, effectively erstwhile bonobo-matriarch here with a bit of good news. Last Wednesday evening, I signed the written offer for a new job: that of regulatory medical writer at a major biotechnology company in Cambridge, MA with a tentative starting date of July 26. On Thursday, I quietly scuttled off at lunchtime to go pee in a cup for the pre-employment drug screen. On Friday, I gave 2 weeks notice to my current employer.
When I moved to New Jersey in 2004, I told myself that my long-term plans included moving back to the Boston area. So this is happening just a bit sooner. The family is gung-ho about returning even if the move will be a freakin’ nightmare. Well, most moves are like that.
I’ll miss certain things about Jersey: martinis at Mediterra in Princeton with my friends, ripe tomatoes, sweet corn and peaches (oh, those Jersey peaches!), the ability to visit NYC easily, and walks through the woods that border my home. My current employer, a small CRO that focuses on oncology clinical trials, provided excellent training for me, and I have considered these past two years with the company to be much like a post-doc. Nonetheless, whenever I left Boston after visits over these past six years, I always felt melancholy as if I were leaving my hometown to return to a place where I really did not quite belong. But now? Well, it feels like I am going home again: I’m shipping up to Boston!
This is not surprising. A Consumer Reports survey of over 1,500 Americans with clinical depression suggests that far more people embrace pills than embrace talk therapy, despite the fact that those who attended at least seven therapy sessions reported as much symptom relief as those who relied on drugs alone. Four in five respondents, in fact, replied that they would rather go the pharmacological route.
This is understandable, given that taking a pill as a lot less work and, in many cases, is a lot cheaper than visiting a therapist. But this doesn’t take into account efficacy, and many people have spent years trying to find an SSRI or other drug that produces the desired effects.
Of course, this is a false dichotomy, since many people on medication are also in therapy. But it’s clear that people are hungering for a magical solution to a complex problem, and it’s unlikely that clinically depressed people will ever fully return to baseline using pharmacotherapy alone.
Of ancillary note: More and more people who seek help for mental-health problems report anxiety as one of their symptoms, and the type of therapist people employ (psychiatrist vs. psychologist vs. social worker, etc.) does not appear to have an effect on the efficacy of therapy.
My mother takes a cholesterol-lowering supplement called Multi + CholestOff that is manufactured by a company called Nature Made. Under the name of the product on the package appears the claim “Lowers Cholesterol Naturally.” If you’re getting the idea that this product is being marketed as a pristine and healthier alternative to synthetic or “artificial” medications, great. That’s what Forbes Medi-Tech (the parent company of Nature Made) wants you to think, and they also want you to accept out of hand the premise that “natural” categorically equals better.
An e-mail this morning from one of my former Univ. of Wisconsin-Madison classmates informed me that JoAnne Stubbe, Novartis Professor of Chemistry, Professor of Biology at the Massachusetts Institute of Technology, and who was the first woman to achieve tenure in the biochemistry department at the UW-Madison, received the National Medal of Science from Barack Obama yesterday.
JoAnne is a fiercely brilliant woman who intimidated the bejeebus out of me when I was a fledgling grad student and later as a callow post-doc. She was one of five professors (including my advisor) who raked us over the coals during student research seminars. I also faced her wrath when I overtightened the valve to her lab’s French press. But later, when out and about in the real world, my encounters with Professor Stubbe were nothing but good. She’s funny, intense, and passionate about science. She’s a superb intellectual role model, and even though she was not my advisor, she nonetheless influenced me along with many of us in the biochem. department at the UW-Madison. Her award is a such fantastic and well-deserved achievement!
She was at the vanguard of women entering academia and industry in disciplines like chemistry and physics which were long dominated (and still dominated) by men, but these awards as well as the Nobels with 3 women winners in the sciences this year, including Elizabeth Blackburn and Carol Greider for telomeres/telomerase, indicate that “an old girls” network is forming at last.