the last couple of days

Jonah has had a rough couple of days. Yesterday morning, he just woke up mad and pretty much screamed and cried all the way through bath and dressing change. And then it was off to the Pediatrician's Office for his 18 month check-up. NOT FUN. He was inconsolable the majority of the time. He had to get a shot, screamed any time the nurse or doctor touched him, and needed blood work done. There's a list of things he needs checked at least annually, and it's been a good while since he's had any done. We can't adjust his iron, vit c, zinc etc until we know where his levels are now. Anyway, I unwrapped his only good arm, four of us held him down, the vein was ornery, it took five to ten minutes to get any blood, and then the little bit we did get immediately clotted and was useless. It was a disaster and Jonah was hysterical. We didn't try again. He had had enough for one day.

He then came home and took a two hour and 45 minute nap. Max for him these days is about an hour, so I know he was worn out.

When he got up, he finally ate lunch (at 4 pm), and then we went over to our friends' house for dinner. Jonah seemed to be back to his mostly happy but slightly fussy and clingy self, and we had a good time.

Their son, David, is only about a week younger than Jonah. He is super cute!

Micah is a trip!

Elizabeth is IN LOVE with Matt. She is a huge flirt, and I'm concerned for her parents when she's 14. (Look at that vein poppin' out. She was SERIOUS about her crush.)

Don't be fooled. Matt thought she was pretty cute too.

Jonah had fun playing with different toys and hanging out with other kiddos. This is the last photo I took before my camera battery died. He never quite figured this toy out.

But then, this morning, over the monitor, Jonah woke up with a horrible sounding cough. Just out of the blue. It was more like a bark than a cough, and it sounded like it hurt. He just wasn't himself today.

Poor thing. Throughout the day, his breathing got more stuffy and he started to run a low grade fever. I took him back to the pediatrician this afternoon. More screaming fits ensued as she checked his throat and ears and listened to him breathing. She sent us to an imaging office to get xrays of his lungs and trachea. You can imagine how well that went over given the last two days and what Jonah had been put through. We then had to head back over to the Pediatrician's office (it was well after 5:00 by this time) to await the results.

Jonah has Croup and is being treated with a three day dose of steroids. Dr. B was hesitant and just wanted to know for sure before she prescribed them, as she says the steroids suppress his immune system and was worried about his wounds getting infected. But the EB folks I've talked to say the steroids usually help heal the boo boos, so hopefully it will be a good thing all the way around.

But if you feel like praying a few extra prayers for Jonah, you could pray for good rest, longer naps (one hour a day is not enough for him to stay happy and healthy), that he resists infection, and that his inflammation/coughing doesn't cause any blistering in his airway. All the coughing is also causing him to throw up a lot more (three times today), so we're running Pedialyte in his pump tonight instead of water.

While you're praying, I would really appreciate you lifting up my friends, T and J and their families. T is losing her battle with cancer and will be meeting Jesus very soon (most likely within the next week), and my friend J is fading fast after a long battle with ALS. Both of these women have been huge spiritual influences in so many people's lives, and saying they will be greatly missed is a huge understatement. Many hearts will be broken in their passing. But we will also be so happy that soon their suffering will be over, and they can finally be healed and whole, dancing on the Streets of Gold. Please keep their families, especially their husbands and children, in your prayers.

(UPDATE: I just found out that J passed away this afternoon/evening. Please, please lift up her family.)

As always, many, many thanks.

pat the toilet 1-2-3

Jonah discovered the toilet today. Thankfully, he discovered it with the lid closed. He loved the sounds his hands made patting the top.

This may be my favorite photo I've ever taken of him.

He then made his way from the bathroom to the bottom of the stairs.

He made it up the first step...

... but then wanted down.

So, naturally, being the compassionate and understanding mother that I am, I put down my camera, went behind him and took the moment to physically therapize him by making him climb the entire staircase. He was ticked but he did great, and he was so, so proud of himself when he made it to the top. Totally worth it!

We had a nice day today. We made it to church and then I went to Whole Foods for some full fat, high protein yogurt, and the rest of the time, we've just been hanging around the house. Matt had his Fantasy Football Draft tonight. Not sure how much prep time he put into it this year, but I'm fairly certain it was comparable to last year. If you missed last year's post on what Fantasy Football is like in my house, it might be worth reading... I know many of you can relate.

Alright, that's it for me. Happy One More Week Closer to Fall! (I heard rumor that they have pumpkins and mums outside of Kroger. Can I get a what-what?!)

a good weekend

We've had a GREAT weekend so far. Yesterday was Jonah's Half Birthday, so we thawed out part of his leftover birthday cake (we still have the entire white chocolate top tier left... this was the leftover vanilla layer), and had an impromptu pizza/cake dinner with our neighbors.

They live two houses behind us, and have two girls, four and 14 months. Their sweet mommy brought them over to play yesterday and, honestly, it was the best half birthday present Jonah could have gotten. He was so excited he just yelled and yelled, and they were so great playing with him. This is Emma. I wanted a better photo, but every time I tried to get them together, my camera wouldn't snap (curse you D40, curse you), and Emma would take off.

Today we had arranged for Mom to watch Jonah so we could go look at some used vans. And guess what? We got one of THESE!

Yep, a Sienna! I didn't think there was any way we could afford a Sienna, but it's an '07, and we got an awesome deal. And they gave us a better interest rate than we had found on our own and way more for our trade-in than I thought we'd get.

It was a comparable price for an 09 Dodge Caravan with about 30,000 miles or the 07 Sienna with 50,000 miles. Ultimately, we chose Toyota over Dodge, and I'm glad we did. I don't think we could have gotten a better deal. I'm so incredibly thankful. Before we went in, I prayed something like, "God, please help us not be idiots and give us a salesman that isn't a schmuck." I know. I'm an excellent pray-er. But honestly, all joking aside, I really do feel like God was in this. Our salesman, Cosme, was from Ecuador and has only been here for two years. We spoke in Spanish just as much as we did English. He was so wonderful and when we told him about Jonah, he explained that he knew how we felt because he has a son with CP. I really do feel like he got it. We didn't feel pressured and stood our ground about the price we needed, and I'm just really happy with how it all turned out.

Jonah, meet Sienna. Sienna, Jonah.

And our two requirements for the van:

Rear air controls.

And stow n' go seats. (I was too lazy to take the strollers out to show them stowing and going.)

Matt and I currently have to wear jackets in the car because we have to keep the air on full blast for it to reach Jonah, so I'm so happy about rear air conditioning. Now he can be plenty cool enough, and I won't have to shave my legs every other hour. Ladies, you know what I'm talking about. AND the van has a luggage rack, so we can still use our canvas roof top carrier when we travel. The captain seats don't stow, but they roll forward (back to back with the front seats), so we will have SO. MUCH. SPACE. And we need it so badly. It's going to be a dream compared to how we've had to travel in the past.

And to top it all off, now we're JUST THIS COOL.

CAN YOU EVEN HANDLE IT?

DotW Talks Pickles

With all due respect to our FOTF brethren, DOTW may take the occasional vacation from writing intros to our columns, but we somehow manage to put out a weekly edition with astonishing regularity. (In other words, none of that every-other-week stuff, you slackers.)

We do find ourselves in a bit of a pickle this week, with deadlines looming for IN VIVO, START-UP, and our annual Pharmaceutical Strategic Alliances meeting. (You’re coming, right?)

Mmm, pickles. In an ideal world we would simply be referring to a piquant condiment perfect for enlivening pedestrian burgers and dogs in what may be one of the last opportunities of the summer grilling season. But a whole lot of folks found themselves in a barrelful of briny situations this week. Let us dive in.

For starters, how about Jazz, Immunogen/Roche, and EpiCept, which all woke up on the wrong side of the FDA regulatory bed? Throw in Novartis, which still has to woo those pesky independent Alcon shareholders to its cause without shelling out an additional bolus of cash. And squirt on a little Sanofi-Aventis, which not only lost the first round in its fight to stop a Lovenox biosimilar but also can’t seem to seal a deal with Genzyme.

Better add Inspire Pharmaceuticals to that mix as well. This week Inspire amended its partnership deal with Allergan for late-stage dry eye therapy Prolacria. No surprise, really; back in January the company reported Prolacria failed to show efficacy in a Phase III clinical trial, and it's no secret revised deal terms typically follow in a partnership that suffers a clinical setback.

But the revision is a little more complicated since the Prolacria failure also triggered an amendment in the two companies' ongoing relationship for Allergan’s Restasis. To summarize some ancient history, Allergan and Inspire first teamed up in 2001 to develop dry-eye treatments in a deal that gave Inspire the right to co-promote Restasis. In 2008, Inspire withdrew from the co-promote, but still received royalties on the Allergan medicine at the same rate as before. But there was a very big hook.

The royalty rate was good only as long as Allergan and Inspire continued to work on Prolacria. Now ith no new plans for a study, Inspire will get less of the revenue pie from sales of Restasis and “any other human ophthalmic formulations of cyclosporine owned or controlled by Allergan." The upshot? Look for Inspire to focus instead on its denufosol and Azasite programs.

To avoid your own deal-making pickle (or even a jam), we bring you another edition of...

Roche/BioImagene: In a bid to keep locking up capabilities in personalized medicine, Roche, via its Arizona-based Ventana Medical Systems, this week took out the privately-held digital pathology start-up BioImagene in a deal worth $100 million. The take-out comes just two years after BioImagene investors put $26 million to work in a Series D financing, the small company’s only disclosed fund raising since its inception in 2003. Backers of the company include Burrill and Co., Ascension Health Ventures, Artiman Ventures, and Siemens Venture Capital, the corporate venture arm of industrial giant and competitor to General Electric. Indeed, that Roche won the small firm, known as a leader in pushing pathology into the digital realm, was somewhat of a surprise. Given Siemens’ involvement in the 2008 financing, its presence in imaging markets and its ambition to become a one-stop-shop for medical testing, the odds in Vegas probably didn't favor Roche as the buyer. Still, the deal is a strategic fit for the pharma, since it complements the pathology offerings already in-house as part of Ventana. Moreover, it enhances the Swiss company’s cancer workflow offerings, providing a service element that’s become increasingly of interest to imaging companies, diagnostic players, and even life science tools providers.—Ellen Licking

Procter & Gamble/Somaxon Pharmaceuticals: Somaxon is finally ready to launch the insomnia drug Silenor (doxepin) now that it has a co-promotion partner, Procter & Gamble. The San Diego specialty pharma announced the commercial arrangement Aug. 25, five months after Silenor received FDA approval. Under the agreement, the two companies will launch Silenor in September with a combined U.S. sales force of about 215 reps. P&G will provide about 105 reps who will promote Silenor to targeted primary care physicians and pharmacies, while Somaxon’s team will market to specialists and "top-decile physicians who treat insomnia," the firm said. For its efforts, P&G will receive a combination of fixed fees and royalties on U.S. net sales of the drug. In a same-day conference call, Somaxon CEO Richard Pascoe estimated P&G's take would amount to no more than 15% of the drug's annual net sales. The deal seems like a win for P&G, which made no upfront payment, and also gained an interesting downstream perk -- the right of first refusal to develop and commercialize Silenor as an over-the-counter product.—Joseph Haas

Roche/Aileron: On August 23, Roche announced it would collaborate with privately-held Aileron to use the biotech’s proprietary stapled peptide Pepducin technology to develop drugs against five unnamed targets, some of which have yet to be chosen. At north of $1 billion, the bio-bucks are eye-popping, but the specific deal terms don’t exactly break new ground the way Alnylam’s non-exclusive licensing deals with various pharmas or Celgene’s partnership with Agios have done. The five-target arrangement, centered around oncology and other therapeutic areas, is heavily back-end loaded, worth just $25 million upfront. It does, however, provide Aileron with additional validation and could be the prelude to a larger deal. As such, the deal provides Aileron with always welcome additional undiluted capital, and preserves its exit options. Aileron, which has raised around $60 million, wasn’t exactly hurting for cash. The company has commanded attention not only for its high concept science and platform capabilities, but also for its roster of four corporate backers, once again illustrating the importance of strategic investors in funding early-stage science.—Paul Bonanos and EL

Cypress Bioscience/Alexza; Cypress/Marina Biotech: Even as it continues to fight a public battle with hedge fund operator and minority shareholder Ramius, Cypress Bioscience inked a pair of small deals this week. The specialty player announced it would acquire rights to Marina Biotech’s autism drug for $750,000 upfront, plus milestone payments. It also licensed a preclinical smoking-cessation product from aerosolized CNS drug maker Alexza Pharmaceuticals. The agreement is worth $5 million upfront plus a $1 million milestone-based tech-transfer fee and includes a carried-interest fee in the event of a future acquisition of rights to Alexza’s Staccato technology for nicotine, an inhalable delivery system with electronic dosing controls intended to help smokers kick the habit. In the case of the Alexza alliance, Cypress will also pay for Phase I trials of the medicine, anticipated to commence next year. Back in June, Cypress, which markets fibromyalgia drug Savella (milnacipran), paid $30 million upfront to license an anti-psychotic drug candidate from Israel-based BioLineRx in a deal that also includes milestones. That partnership prompted a hostile takeover attempt last month by Ramius, which harshly criticized Cypress’ management and its acquisition strategy while offering $4 per share to acquire the company.--PB

Isotechnika/3SBio: Isotechnika announced an agreement Aug. 24 with 3SBio covering sales of Isotechnika's lead candidate voclosporin, a Phase III compound that helps suppress the immune system's rejection of transplanted organs. 3SBio will pay $1.5 million upfront to license voclosporin for transplant and autoimmune indications in mainland China, Taiwan and Hong Kong. The Chinese firm also will invest $4.5 million in Isotechnika via a three-year convertible debenture and will be responsible for clinical development, registration and commercialization in China. Interestingly, 3SBio also got the right to develop voclosporin products in other indications (including presumably ophthalmology where troubled Lux had worldwide rights via a 2006 deal.) 3SBio CEO Lou Jing said his company would work with Isotechnika to apply for approval from the Chinese State FDA for a Phase III trial inside China. 3SBio has become one company biotechs can look to for China-only licensing deals. Previously, 3SBio licensed Chinese development and marketing rights to AMAG’s chronic kidney disease drug ferumoxytol.--JH
Image courtesty of flickrer gadgetgirl used with permission through a creative commons license.

UPDATED TUESDAY 08.31.2010. Due to an editing error, IVB inappropriately referred to Aileron's peptide technology via the proprietary trademarked name of Anchor Therapeutics.--EL

Jail Time for Pharma Execs? IN VIVO Blog Readers can Relax

There's lots of buzz right now about the potential for FDA to seek jail time for executives involved in quality control problems. This piece on CNN.com, for example.

Readers of the IN VIVO Blog, however, have nothing to worry about. For the past two years we've been noting the calls for executive accountability, and comments by FDA officials and others about their sweeping ability to hold top executives responsible for failures they may not even have been aware of under the so-called Park doctrine. (Start here or here).

So all of you can relax, because you made sure that your compliance with FDA standards is beyond question.

Didn't you?

18 months today

Hey Everybody! It's me, Jonah!

Today I turn ONE AND A HALF years old. I'm getting to be such a big boy!

I weigh over 25 pounds now, and I've jumped from the 25th to the 75th percentile. Mommy says it's 'cause of all that avocado and flaxseed oil she's been giving me. I've had many eating ups and downs (mostly downs), but we're so thankful for the g-tube, so I can get all the nutrition I need, no matter what. Mommy's just started giving me some yogurt, again, once a day, and it's going pretty well. I sleep about 11 hours a night and take one nap a day. It's not that long (45 minutes to an hour and a half), but I stay in a good mood most days, so Mom doesn't mind too much.

I can crawl all over the place now. And guess what? I can pull up to standing now!

My favorite toys are still (and always, forevermore) my ball popper...

my stacking cups and shapes, any ball, this new toy that my Nana got me that's a fun light-up wand sort of thing, and books. I LOVE BOOKS, especially the kind with flaps. I'll sit and let Mom and Dad read to me. My favorite books are "Barnyard Dance," "Peek-a-Boo I Love You," "A Cuddle for Little Duck," "Mr. Brown Can Moo, Can You?" and "Where's Baby's Mommy?" I love music and anything with a rhythm. My favorite shows are "Yo Gabba Gabba," "Wonder Pets," and "Jack's Big Music Show." I also like "Curious Buddies."

One of my other favorite toys is my new activity table. I love it and it's the perfect height for kneeling or standing.

I'm getting more interested in non-toys these days. I love to explore, and am really learning that I can get into things. I love playing in the dishwasher and trash can. I'm such a fun age right now. I've learned to give hugs and kisses. I go "mm-mmm" when I give hugs, and I give great kisses.

I'm becoming so affectionate, and Mommy thinks I like snuggling and hugging more than ever. When Mom or Dad sit or lie down on the floor, I just can't stop myself from laying my head in their laps or crawling all over them. My favorite time of day is right before bed when Daddy takes me upstairs and we read books and play basketball. It's our "Man Time," Daddy says, and I love it. Last night he was teaching me how to throw my hands up and say, "Touchdown!"

I'm repeating lots of things. I'm not consistent in what I say, but at one time or another, I've said or repeated: dog, kitty, baby, bear, hello, bye-bye, ten, circle, moo, ha-ha-ha (what a monkey says), meow, pop, ball, daddy, up, down, nana, shaina, granny, and deac. Mommy thinks that's it but she may be forgetting some. She thinks maybe I said "mommy" yesterday, but she's not sure. She doubts it. I like to drive her crazy like that.

These last three months were busy and exciting. I guess the biggest thing is that this is the first time I've ever made it from well visit to well visit without having to go to the doctor's office. I've been so healthy!

In other news, Mommy gave me my first full hair cut...

I got to go to the Children's Museum for the very first time...

and to the beach (for the second time, but I don't really remember the first)...

I got to go swimming for the first time (LOVED it!)...

And I got to take my first stroll by the ocean...

and Mommy bought me my very own big boy shoes (even though she still calls me her baby)...

The hardest thing about the last three months has been the heat. It has been H.O.T. We hardly go outside at all, except to check the mail. I spend my days longingly looking out the front door...

waiting for the day I can break outta this joint...

I'm enjoying getting out more and more, although I'm still a little apprehensive in new places. I still like going to Target, the grocery store, and I love going to church and playing in the nursery. I'm not ready for Mom or Dad to leave me there yet, but I'm getting more comfortable. Mommy can't wait until the Fall when we can get out and EXPLORE. She has big plans for us, including but not limited to: the zoo, a pumpkin patch, every park in Forsyth County, the Farmer's Market, the fair, and restaurants with outdoor seating. We can't wait. I mean, our house is cozy and all, but enough already! We want OUT!

It's been a great three months, and Mom and Dad know that the best is yet to come. They just love me so much, y'all. Sometimes it's almost suffocating...

How embarrassing. They are so proud of me and can't believe how far I've come and all the things I've accomplished. They thank God for me all the time and can't wait to see what He has in store for me. They know it will be something great and are so excited for my future.

And guess what else? Mommy says we get to eat the rest of my amazing birthday cake tomorrow. I mean, they'll eat it. Me, not so much. Who do you guys think I am? Let THEM eat cake.

Thanks for praying for me and following my story and letting everybody know about EB. I'm doing so well, resisting infection, gaining weight, breathing easy... all because of the prayers you've prayed. Mommy, Daddy, and I just can't thank you enough. You're loved and appreciated. So, THANK YOU!

Financings of the Fortnight is... the Most Interesting Biopharma Column in the World

FOTF never really goes on summer vacation, unlike those namby-pambies over at DOTW. But as befits the Most Interesting Biopharma Column in the World, we constantly travel far and wide. And when we travel we cannot help but meet other Most Interesting People who want to discuss all manner of things, from protein folding to peregrine falcon migration patterns to the amyloid hypothesis to American trade policy.

Despite having vocal cords that have addressed the United Nations General Assembly and performed Tristan und Isolde -- all in one day -- even we sometimes overdo it. This morning, after a night spent deep in conversation with three well-funded post-doctoral frauleins under the glow of poolside tiki torches and a gibbous subtropical moon, we felt slightly hoarse and downed an emergency anti-logorrheic. (That means this week's installment is short and sweet.)

Still, we can't help but note that all four editor's picks this fortnight underscore the changing nature of biotech venture capital. Heavily tranched rounds are now a mainstay, and perhaps here to stay. We've got two of 'em for you. We also profile an unusual PIPE with four participating VCs who are usually as private as private can be, and word from the feds that the Department of Health and Human Services wants to start a pandemic/emergency/countermeasure venture fund. They'd be wise to check in with Kleiner Perkins, which launched its own $200 million "flu fund" in 2006.

Stay informed, my friends, and when you read about biopharma financing, make sure it's...


Anchor Therapeutics: The peptide drug developer closed on $10 million of its Series B round from inside investors, with a new goal of $15 million – half its original target of $30 million. The company hopes new backers will join TVM Capital, HealthCare Ventures and the Novartis Option Fund, who supplied the first tranche of the new round as well as $19 million in Series A funding in 2008. “A little bit of setting goals is testing the market and seeing what the reality is,” CEO Rick Jones told our Pink Sheet colleagues. Anchor is developing candidates called "pepducins" to selectively bind to G protein coupled receptors. Anchor hopes its pepducins can trigger specific responses inside the cells and avoid side effects often associated with small molecule drugs targeting the receptors. Anchor's most advanced program is a CXCR4 agonist designed to attract stem cells to accelerate healing in fractures and myocardial infarctions. Novartis maintains an option agreement with Anchor that includes over $200 million in potential milestones as well as royalties. -- Shirley Haley and Paul Bonanos

Taligen Therapeutics: Taligen collected a $10 million tranche of its massive $65 million Series B round, bringing to $36 million the contributions of Sanderling Ventures, Clarus Ventures, Alta Partners and High Country Venture since 2008. That’s on top of a $4 million Series A and a small seed round, all in support of Taligen’s development of therapies that target the alternative pathway of the complement system, a surveillance system employed by the body to attack and clear pathogens that may go awry in certain inflammatory diseases. Taligen also revealed a broad patent on its compound TT-30, a replacement of the Factor H protein that regulates reactions in the complement pathway. CEO Abbie Celniker told The Pink Sheet that Taligen is likely to bring TT-30 into Phase I for an unspecified orphan disease in the fourth quarter of 2010. The compound is said to be applicable to a range of indications including age-related macular degeneration, atypical hemolytic uremic syndrome, and paroxysmal nocturnal hemoglobinuria,. Taligen is actively seeking a partner for its ophthalmic program, but expects the rest of its promised Series B money will help it take an in-house candidate into Phase III on its own. -- PB

Achillion Pharmaceuticals: Months after bringing in $22.9 million in a follow-on public offering, Achillion turned to venture capital investors to raise $50 million in a warrant-heavy PIPE financing. At least one, Clarus Ventures, has backed the anti-infectives developer before. Under the deal, announced Aug. 18, Achillion sold 19.755 million shares of common stock at $2.49 per share, its closing price as of Aug. 17. But for an additional $0.125 per unit, buyers also received seven-year warrants to buy 0.35 shares in the New Haven, Conn., firm for an exercise price of $3.1125 a share. Structuring the financing this way put Achillion on the hook to issue another 6.921 million shares, resulting in stock dilution that analyst Brian Skorney of ThinkEquity LLC said would add 69 percent to company’s share count as of second-quarter 2010. “The return to a more venture capital-based investor structure somewhat mitigates the benefit of the raise and will effectively decrease share liquidity,” he wrote in an Aug. 20 note. Joining Clarus, which participated in a 2008 PIPE that netted Achillion $29.5 million, were Domain Associates, Quaker BioVentures and Pappas Ventures. Achillion said it will use the proceeds to move lead candidate ACH-1625, a protease inhibitor for hepatitis C, into Phase II in September, while bringing two other HCV compounds, pan-genotypic protease inhibitor ACH-2684 and NS5A inhibitor ACH-2928, into the clinic in early 2011. -- Joseph Haas

Medical Countermeasure Strategic Investor: As part of a broad review of US medical countermeasure strategy released Aug. 19, an HHS committee is recommending the creation of a government-backed $200 million venture fund to boost startups working on products critical to medical emergencies, terrorist attacks or pandemic outbreaks. Different than BARDA, the agency charged with dispensing so-called "Bioshield" funds to build the national emergency stockpile, the countermeasure fund would invest in companies, explained National Institute of Allergy and Infectious Diseases director Anthony Fauci at a press conference. Known for now as MCMSI, the fund needs Congressional authorization. It would focus on companies developing new drugs to fight multi-drug resistant organisms, novel mechanisms for disrupting pathogenesis through host pathway targeting, and multi-use platform technologies for diagnostics, vaccines/prophylaxis and therapeutics, according to the review report. (The full HHS review is available here, with the MCMSI section on page 15.) As proposed, the fund would operate independently of the government and try to leverage private capital. The HHS committee cited as a relevant model In-Q-Tel, a CIA-funded firm that invests in intelligence high-tech. -- Cathy Dombrowski and Alex Lash

Photo courtesy of flickr user TreyDanger.

photos

Crazy hair, dirty bandages, about to get nudey. Good times.

All clean in his Grouchy Smurf t-shirt. (Thanks, Aunt Kim!)

I love this kid.

The best part of my day - Jonah Kisses.

I don't really know, but I thought it was funny.

He loves his Leap Frog Activity Table from his friends, Carston and Caroline.

Today's been okay. Jonah had his psych evaluation today. I was pretty skeptical, because, honestly, how do you evaluate an 18 month old? But it went well. Really, she just talked to me about all the issues Jonah's had, his reflux, current schedule, and how feedings are going now. We both agree that we need to take it slowly, not push him too hard, and have small goals. She agrees that his aversion is mostly driven by his negative experiences from severe reflux (I'm so tired of the puke), and that it's the one thing in his life he feels like he can control. It was very helpful, actually, and I'm glad to have focus, a plan, and someone who is trying to understand all sides of the complexity that is Jonah and eating.

We have some friends coming tomorrow afternoon, and I'm excited that Jonah gets to socialize with some kiddos.

Well, it's been a busy day and I didn't sleep well last night, so I'm off to bed. Goodnight.

convicted

Between this post by my friend, Meredith, (seriously, go read it) and this video...





posted by my other friend, Meredith, I'm feeling convicted today.


Don't you hate/love it when God smacks it right in your face like that?

Wolfe vs. Rappaport: A Standoff Between FDA and One of Its Advisory Committee Members

There was some disharmony at Jazz Pharmaceuticals’ FDA panel review of its drug Rekinla for fibromyalgia.

FDA’s Arthritis Drugs Advisory Committee and Drug Safety & Risk Management Advisory Committee voted 20-2 against recommending Rekinla (sodium oxybate) for a supplemental indication for treatment of fibromyalgia on August 20; sodium oxybate is currently approved for the reduction of daytime sleepiness and cataplexy in patients with narcolepsy under the trade name Xyrem. (See our coverage in "The Pink Sheet" DAILY, here.)

Anyone that has been to an FDA panel meeting knows there are ebbs and flows that contribute to the final outcome.

One of those critical points came in the late morning during the FDA question and answer session, following the agency’s formal presentations.

Enter Drugs Safety & Risk Management committee member and outspoken drug industry critic Sidney Wolfe (director of Public Citizen’s Health Research Group). Wolfe explained that he had obtained publicly available documents that cast negative light on the trustworthiness of the sponsor to responsibly market Rekinla if the panel delivered a positive recommendation and FDA approved the drug.

To resolve parallel criminal and civil allegations of off-label marketing for Xyrem by their Orphan Medical division, Jazz entered a guilty plea and paid $20 million in monetary penalties as part of a settlement with the US Attorney’s Office for the Eastern District of New York. (To view the press release, click here).

Committee Chair Kathleen O’Neill (University of Oklahoma College of Medicine) tried to cut Wolfe off, saying the session was only for questions to FDA and could only address the material in front of the panel on that day.

Wolfe continued to read a summary of the off-label marketing settlement and said he eventually would have a question.

With Wolfe unwilling to stop reading, FDA took the seemingly unprecedented action of cutting off Wolfe’s microphone. That step has become routine during the open public hearing where there is a time limit but this was one of their own advisory committee members.

Wolfe turned the microphone back on and finally got to his question: Why, he asked, did FDA not mention the Xyrem off-label settlement in its presentations to the committee? After all, he argued, it was relevant to the decision at hand: could the sponsor be trusted to market Xyrem—also known as gamma-hydroxybutyrate (GHB)—to a much broader indication than it was already approved for?

FDA Division of Anesthesia & Analgesia Products Bob Rappaport stepped in and first instructed Wolfe to stop talking when the panel chair requests that he stop talking, explaining that it was her prerogative.

Rappaport continued that Wolfe’s reading of the documents were the first time he had ever heard of the off-label case and that it was not relevant to the Rekinla review despite the fact that both Xyrem and Rekinla are the same drug (sodium oxybate). Rappaport then admonished Wolfe for not providing the documents to FDA earlier, noting that he had called FDA's advisory committee management staff earlier in the week to raise an issue, but not provided the information he was reading at the meeting.

[UPDATE: Wolfe tells us "I had never previously told FDA officials that I had obtained these documents since I assumed, as it turned out incorrectly, that they were aware of them because FDA's Office of Criminal Investigation had been involved in the criminal prosecution. Why they were unaware, as Rappaport said, is another issue."]

The drama appeared to have come to a close with Rappaport’s comments; however, the FDA official returned after the lunch break and the open public hearing with a prepared statement:

“The issue that Dr. Wolfe raised this morning is a matter related to compliance and is not related to the topic under discussion today, unless there has been an accusation of data integrity problems with this application – and I’m not aware of any data integrity concerns. The only other way that the case referred to by Dr. Wolfe could be pertinent to this application would be if it was brought up to impugn the sponsor in the hopes that the committee would be punitive towards them in your deliberations and recommendations regarding this application. However it is important for you to recognize that that would not really be punitive to the sponsor but would really be punitive to the patients.”

At that point, Jazz Pharmaceuticals' Chief Compliance Officer Janne Wissel added a few remarks.

"We do have a corporate integrity agreement because we assumed responsibility for the acts of Orphan Medical at the time we purchased the company. The Department of Justice, as well as the OIG concluded at the end of their investigation that the behaviors of Jazz Pharmaceutical were not the same as those of Orphan Medical. However, we assumed responsibility for those actions.

"We have completed three years under our corporate integrity agreement where we have reports that are based on information and an audit conducted by an independent review organization with respect to our compliance for promoting our product within our labeling. All of those reports have concluded that we are promoting our product within labeling and that we are compliant with respect to the aspects of our corporate integrity agreement."

Wolfe was not given an opportunity to respond at the meeting, so we asked him if he would care to after the fact. He emailed us the following statement:

The previous RiskMap program and the Xyrem Success Program, that were agreed upon in 2002 by Orphan as a condition of approval of Xyrem for narcolepsy, included extremely restricted distribution through one pharmacy, education of doctors and patients and a registry of patients getting the drug.

One of the questions our advisory committee was being asked to respond to was the adequacy of the new REMS program for the expanded use of oxybate for treating fibromyalgia .

Xyrem’s manufacturer, Orphan, violated the above mentioned restrictions on distribution by illegal, criminal off-label marketing and was successfully prosecuted for this. When I discovered this, a week before the hearing, I assumed that the reason why it was not included in the Advisory Committee’s briefing materials was that for some reason the FDA did not want us to know about it. This seemed peculiar, since the prosecution of the company seemed quite relevant to our evaluation of whether the new REMS program could be expected to be effective.

As I asked in my question to FDA, following the material I read from the US Attorney’s prosecution of Orphan, Why didn’t the agency provide the material to us?

Dr. Rappaport’s surprising answer was that they were not aware of the criminal prosecution. He later added that this was really a matter involving FDA compliance and that it was not “related” to the issues being discussed by the committee because it did not involve data integrity.

Although it is the compliance part of FDA that was involved in investigating this (the FDA Office of Criminal investigation was also involved), the idea that the details of this criminal prosecution involving violations of the agreed-upon restricted marketing of this dangerous drug were not relevant to our deliberations seems irrational.

Dr. Rappaport went on to say that since it was not relevant to our discussion, the only reason I brought it up was to “impugn the sponsor” and thereby turn the vote against them. This would, he said, “not really be punitive to the sponsor but would
really be punitive to the patients.”

Following Dr. Rappaport’s after-lunch statement, Jazz Pharmaceutical, the owner of Orphan since June, 2005—including, according to the US Attorney, for at least seven months while the illegal activities were occurring--stated to the Advisory committee that the company had been essentially exonerated by the US Attorney’s office and was under a corporate integrity agreement with the HHS Inspector General. This statement, like Dr. Rappaport’s, is also incorrect since, in its non-prosecution agreement with Jazz, the US attorney stated on July 13, 2007:

“Based on the evidence gathered during this investigation, the government maintains that it would be able to prove that JPI [Jazz Pharmaceutical Incorporated], as a consequence of the criminal conduct committed by its subsidiary Orphan ("the Unlawful Conduct"), is likewise guilty of introducing and causing the introduction of a misbranded drug into interstate commerce, in violation of 21 U.S.C. 331(a) and 333(a)(2).”

It’s unclear how much of an impact the Wolfe-Rappaport discussion had on the final 20-2 negative vote for Jazz. But it’s clear the public disagreement was a notable turning point in the panel deliberations.

The agency later said “the issue raised this morning by Dr. Sidney Wolfe related to Jazz Pharmaceuticals marketing practices and compliance activities for sodium oxybate is not related to the topic (that was) under discussion. The FDA weighs all of the comments made by committee members equally but will only be considering the safety and efficacy information discussed today as it evaluates sodium oxybate to treat patients with fibromyalgia.”

--Ramsey Baghdadi