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.

FDA okays drug to cut preterm birth rate

The U.S. Food and Drug Administration this week approved the first drug aimed at reducing the rate of pre-term birth.

Makena, hydroxyprogesterone caproate, is an injection approved to stop preterm delivery before 37 weeks of gestation. It is intended for pregnant women who have had at least one spontaneous preterm birth, and is not advised for use with multiple fetuses, or other risk factors for pre-term birth.

Pregnant Graffiti

One in every eight babies in the United States is born before 37 weeks — 1,500 every day, 13 of whom die from complications.

“Preterm birth is a significant public health issue in the United States,” said Sandra Kweder, M.D., deputy director of the Office of New Drugs in the FDA’s Center for Drug Evaluation and Research. “This is the first drug approved by the FDA that is indicated to specifically reduce this risk.”

A health care provider injects Makena into a woman's hip weekly, beginning at 16 weeks, or no later than 21 weeks gestation.

The FDA approved Makena under its accelerated approval protocol, which requires a drug's manufacturer to continue to research the drug's efficacy and side effects. An international trial is now under way.

Hologic, a Bedford, Mass.-based manufacturing firm that concentrates on women's health, developed Makena, previously known as Gestiva. Hologic recently finalized the sale of the drug to KV Pharmaceuticals of St. Louis, Missouri.

The FDA okayed Makena's use based on a multicenter randomized double-blind trial that looked at 463 women ages 16 to 43 who had a history of preterm birth. Of the subjects treated with Makena, 37 percent delivered their babies before 37 weeks, compared with 55 percent of women in the control group.

The FDA previously approved hydroxyprogesterone caproate in 1956 under the name Delalutin. The drug was withdrawn from the market in 2001 "for reasons unrelated to safety concerns," according to the FDA.

Pregnant Graffiti by Petteri Sulonen

“The Pill” at 50

We're in the thick of the 50th anniversary rumination on "the Pill," which has been blamed for precipitating "the sexual revolution" -- it was hardly the only impetus -- and has probably played a role in lowering maternal mortality as well. In May 1960, the U.S. Food and Drug Adminstration began the process of allowing the pharmaceutical maker G.D. Searle & Company to market its drug Enovid as the first oral contraceptive.

A hundred million women worldwide use oral contraceptives now; where the average American women had 3.6 children in 1960, she now has 2. That's an important figure for our maternal mortality statistics, as the more children a woman has, the more likely she is to die in childbirth.The Pill

Margaret Sanger, who coined the term "birth control," was driven first to become a nurse and then to make disseminating birth-control information her life's work after watching her mother's 18 pregnancies contribute to her death at age 50.

When Sanger began her crusade, the Comstock Law of 1873, an anti-obscenity measure, made it illegal to publish information about birth control, and she was arrested more than once.

In 1936, ruling in U.S. vs. One Package of Japanese Pessaries, Judge Augustus Hand of the U.S. District Court of Appeals in New York exempted birth control devices from restriction under the Comstock Law, which had been absorbed into the Tariff Act of 1930. This was the first step toward making birth control legal. The case came out of Sanger's importation of a shipment of "pessaries," in this case essentially a diaphragm, for distribution through the birth control clinics she had fielded since 1916.

Working with the wealthy philanthropist Katharine Dexter McCormick, Sanger formed the organization that would become the Planned Parenthood Federation of America. (In the spring of 1960, Sanger was 80 and McCormick was 84.)

The researchers John Rock and Gregory Pincus, working first independently and then together, developed an oral contraceptive that they tested in Puerto Rico to get around laws that persisted against birth control on the American mainland.

There have been some great recent stories about the Pill at 50 in the press. I thought Time magazine did a nice job of summing up the pre-Pill atmosphere, the history and today's landscape, and PBS has a useful timeline on birth control from "The American Experience" on its website.

Flashing back to a time when people were arrested for sharing information on birth control is pretty chilling, especially given the fact that it wasn't very long ago.

As Sanger put it, “No woman can call herself free who does not own and control her own body.”

Image from Wikimedia Commons  http://creativecommons.org