A busy day in the preterm-birth drug drama

A great deal happened today in the amazing unfolding drama of a decades-old drug that has been shown to prevent preterm birth:

* KV Pharmaceutical more than halved the cost of Makena, approved by the FDA in February, which debuted at a price of $1,500 per dose. KV Pharmaceutical dropped the price today to $690, and vowed to make sure clinically eligible pregnant women would be able to afford the drug.

* However, the action wasn't enough to stop the March of Dimes from saying it would "step away from" its relationship with Ther-Rx, a subsidiary of the drug company.

"Access (for women) to 17-P is and always has been our paramount concern," Jennifer Howse, March of Dimes president wrote in a letter today to Greg Divis, president of the Ther-Rx Corp., employing a generic term for the drug, hydroxyprogesterone caproate.

In her letter, Howse acknowledged considerable financial support Ther-Rx has given the March of Dimes.

* Sen. Sherrod Brown (D-Ohio) said he was releasing "previously unreported figures showing the scope of taxpayer investment in the development of preterm pregnancy drugs."

A press release from Sen. Brown's office detailed the $21 million he said went into bringing Makena to market, including these costs:

* An initial trial, showing that the injection prevented preterm births in women who have previously had a preterm birth, cost taxpayers $5 million.

* A second trial, at $1.1 million, showed no side effects in children whose mothers had used the formulation.

* A third trial, costing taxpayers $5.1 million, found that the drug did not work to prevent preterm birth in women carrying twins and triplets; according to the NIH, this study was critical for Makena’s orphan drug status determination because an alternative result could have widened the number of potentially eligible women to use the drug.

* A fourth trial, which is still ongoing, cost $7.5 million through Fiscal Year 2010 and aims to find whether 17P treatments are effective at preventing preterm birth in women with shortened cervixes. This is the largest study of 17P by the National Institutes of Health, and could create another category of women eligible for Makena.

But the cost to the public doesn't end there.

In an article in the New England Journal of Medicine last month, Joanne Armstrong MD laid out the cost of treating the roughly 139,000 women she said were likely to need the drug every year. A course of 20 treatments with 17P at $300, the likely price for the drug compounded by a pharmacist, would cost $41.7 million. A course of treatment with Makena (at the original price of $1,500) for one woman would cost $29,000, or $4 billion for all 139,000, many of whom would need to resort to Medicaid to pay for the drug.

The March of Dimes, as saintly in the public eyes as an organization can be, felt the heat from the public for backing KV Pharmaceutical's push for FDA approval of Makena.

"Only after our threats (to boycott March of Dimes fund-raising events) did the MOD firm up their stance," one man wrote on March 25 on the March of Dimes' Facebook page.

But critics, including the Society for Maternal and Fetal Medicine, the American College of Obstetricians and Gynecologists, and the American Academy of Pediatics, saved their strongest language for KV Pharmaceutical.

Sens. Brown and Amy Klobuchar (D-Minn.) asked the Federal Trade Commission to investigate the drug company for "price gouging at the expense of pregnant women."

FDA nixes monopoly on preterm-birth drug

The U.S. Food and Drug Administration on Wednesday took the unusual measure of saying it would allow pharmacists to continue to compound a drug after a new FDA-approved version of the drug debuted in February.

The drug in question is hydroxyprogesterone caproate, which has been around for decades, and has been shown to prevent preterm birth.

The FDA moved to make the drug available in an affordable mode, in light of the fact that the newly approved synthetic progestin, brand-named Makena, produced by KV Pharmaceutical, is going on the market at $1,500 a dose.

When pharmacies compound the "generic" form of the drug, also known as 17P, it typically costs $10 to $20 per dose, according to a press release from the Society for Maternal Fetal Medicine.

In the past, physicians could ask pharmacists to make up a batch of the sterile injectible. However, the FDA ordinarily forbids pharmacy compounding of a drug it has approved.

Indeed, KV Pharmaceutical reportedly sent letters to pharmacies indicating that the FDA would no longer tolerate pharmacy compounding of the drug.

"That is not correct," the FDA declared in its statement.

"In order to support access to this important drug, at this time and under this unique situation, FDA does not intend to take enforcement action against pharmacies that compound hydroxyprogesterone caproate based on a valid prescription for an individually identified patient" as long as the drug is compounded according to "appropriate standards," the statement said.

Drug companies often charge high prices for newly approved drugs to offset the expense of the typically costly, research-laden approval process.

However, KV Pharmaceutical "received considerable assistance from the federal government in connection with the development of Makena by relying on research funded by the National Institutes of Health to demonstrate the drug's effectiveness," the FDA statement said.

"It also obtained seven years of exclusivity under the Orphan Drug Act, obtained approval under FDA's accelerated approval program, and received expedited review," the statement said.

More on this tomorrow.

Fears about VBAC

Taffy Brodesser-Akner's first-person piece in the Los Angeles Times today about her impending birth is a candid, affecting counterpoint to a symposium the National Institutes of Health held last month in Washington, D.C.

With her first baby, born 2 1/2 years ago, Brodesser-Akner endured an emergency Caesarean section after 29 hours of labor, she writes. The experience left her traumatized. Now in the early weeks of her third trimester, waiting to deliver her second child, she is hoping for a vaginal birth after Caesarean, or VBAC.

The VBAC has been the subject of a lot of discussion lately. The NIH held a three-day conference on the topic that encouraged supporters of the VBAC -- and there are many -- by recommending that the VBAC be a more readily available option than it has been in the past.

In her essay, Brodesser-Akner writes, "I agree that women should have the right to try for a VBAC; I'm just not sure if they should try for one. Rather, I'm not sure if I should."

Of women who want a VBAC in a particular pregnancy, she writes, "the more honest and maybe the more uncomfortable way to say it, is that they want to give it a shot. They want a TOLAC, a trial of labor after a C-section."Pregnant Graffiti

Only 60 to 80 percent of women who attempt a VBAC actually get to have that vaginal delivery, Brodesser-Akner writes; the remaining women wind up getting another C-section. And perhaps 1 percent will have a uterine rupture (with a previous low transverse uterine incision, the most favorable for a VBAC; other types of incisions carry more risk), which can threaten the lives of both mother and child.

"When a uterus ruptures...things go wrong fast — and they go wrong big," she writes, adding that a high-risk obstetrician told her that one-quarter of those ruptures end in hysterectomies, brain damage and/or the baby's death.

"As that doctor said to me, 'The risk may be low, but it's 100% when it's happening to you,' she writes.

Brodesser-Akner is right. Every pregnancy is different, and I can assure you from experience that when you find yourself living out that small, shocking statistic, it is 100 percent real. And I am one of the lucky ones.

But why couldn't she be in that 60 to 80 percent of women who have the "normal" birth experience she says she desires? And if she births in a hospital with capable OB/GYNs who perform a good number of Caesareans -- and 24-hour anesthesiology coverage -- she should have the backup she requires in case of an emergency. That shouldn't be hard to find in Los Angeles.

Any birth can take a turn toward the worst-case scenario, and it's impossible to fully predict which ones actually will do so. It is probably all too easy for a woman who had a wretched experience during her last birth to imagine all the things that could go wrong.

But the numbers are with mothers in general; that is, the odds are in their favor. The fact that the pendulum might be swinging back toward a trial of labor in some challenging situations is, I think, a good thing. And I am by no means alone.

I would tell Brodesser-Akner what I tell my own daughters, not only about childbirth but about life in general: Don't let your fears rule your life. Don't be foolhardy, but don't think the cosmos is out to get you, either. I know it's a cliche, but it's true: The most dangerous thing many of us will ever do is ride around in  cars (or worse yet, on bikes), and nobody seems to spend much time worrying about that.

Whatever she decides, I hope Brodesser-Akner has a beautiful birth story to tell this time. It should be one of the best days of her life.

Image by Petteri Sulonen

Can the VBAC make a comeback?

Let's interrupt our Women's History Month programming to consider the news. The National Institutes of Health today begins a three-day session on vaginal birth after Caesarean, a hot topic, given that this practice, which was commonplace 15 years ago, has become scarce in the United States, at the same time that the Caesarean section accounts for nearly one-third of American births.

The VBAC has some passionate champions. While it isn't for everyone, it can work for many mothers, enabling them to avoid major surgery, and perhaps also to enjoy birth as they have always imagined it. The VBAC's decline has attended a steady rise in reliance on the Caesarean section, in part because the VBAC does carry a risk of rupture to the uterus, which can be life-threatening.

So it will be exciting to see what comes out of this conference, which aims to bring the best research available to bear on determining the safety and efficacy of the practice.

The VBAC is also one subject of an article by Denise Grady in the New York Times on Sunday, about a hospital in Tuba City, Ariz., where 32 percent of women who previously had Caesarean sections delivered vaginally, compared with a national average of less than 10 percent.

The rate of Caesarean births at the Tuba City Regional Health Care Corp., where about 500 babies are born a year, is 13.5 percent, less than half the national rate of 31.8 percent. The hospital is run by the Navajo Nation and is partially funded by the Indian Health Service, and it largely serves a Native American population.

What I love about Grady's account is how well this small, poor hospital appears to be doing in addressing one of the major tensions in the modern birth story -- how to keep the blissful experience of childbirth from being swamped by the technology that has been developed to keep it safe.