How do you solve a problem like Makena?

In February, when the Missouri-based Ther-Rx Corp. received FDA approval to market the progesterone injection formerly known as 17P, maternal-fetal health advocates cheered. But now, some of those groups are publicly challenging the product's price, which could reach $30,000 for a course of treatment to prevent preterm labor.

The drug 17-alpha Hydroxyprogesterone caproate, or 17P, had originally received FDA approval in the 1950s for multiple indications, one of which was preventing preterm labor, but it came off the market in 2000 because of a manufacturing issue. After a publicly funded 2003 study of 463 women found weekly injections of 17P effective in preventing preterm labor among women at high risk, the drug gained widespread use, even though practitioners had to order it from compounding pharmacies.

In February, the March of Dimes lauded FDA's decision to approve 17P under its orphan drug program, guaranteeing market exclusivity to Ther-Rx, which will market 17P with the trade name Makena. The March of Dimes praised FDA's decision as likely to standardize the quality and consistency of the product and, presumably, to lessen the "logistical and financial barriers" to patient access, the organization said in a press statement.

And then everyone learned Makena's price. Ther-Rx revealed that each Makena shot would cost $1,500 - while 17P had previously cost between $10 and $50. The ideal treatment starts at approximately 16-18 weeks' gestation and continues until 36 weeks' gestation, so a woman might receive as many as 20 doses of 17P during her pregnancy. Although the company offered to provide the drug free to lower-income uninsured households, the full cost to insurers including Medicaid, could reach $30,000 per pregnancy.

On March 11, the American Academy of Pediatrics, the American College of Obstetricians and Gynecologists, and the Society for Maternal-Fetal Medicine published a joint letter to Ther-Rx. It states: "In our current climate of controlling health care costs in the United States, an added cost of $30,000 for as many as 140,000 pregnancies per year, or 4.2 billion dollars, is a staggering figure."

Dr. Christopher Harman, director of the Center for Advanced Fetal Care and chief of obstetrics and gynecology at the University of Maryland Medical Center, Baltimore, called Makena's pricing "an outrage." In an interview, he said, "This stuff is really cheap to make - this would be as if a brand-new company somehow got a patent on Tylenol or aspirin and decided to sell it at $100 a pill." Makena's pricing "strikes at the core of women at highest risk for preterm birth already" - young African American women. "We may remove their best hopes for having a close-to-term birth."

On its website, the company said: "We appreciate the concerns expressed by multiple audiences and are committed to working collaboratively with all interested parties to make this vital medication even more available and affordable to women across the country."

In a March 17 email, the company said its patient assistance program could aid families with up to $100,000 in annual income, a threshold that could cover 85% of American households. "Based on the feedback we've received, we are currently exploring additional ways to help ensure universal, affordable access for all patients who are prescribed Makena," it said.

Harman said he has been using 17P for about five years in his patients, mostly low-income women in inner-city Maryland, and that between 100,000 and 140,000 women a year are probably eligible for treatment with 17P in the U.S.

"Nobody is saying the company was out to deprive any group of women, but as often occurs when financial decisions are made, they have a disproportionate impact on the people who need the treatment the most," he said.

Other physicians were quick to express anger online when they learned about the price - mostly at the manufacturer, but also at the March of Dimes for supporting Makena's approval.

Dr. Jennifer Gunter, an ob/gyn, author, and pain physician at Kaiser Permanente in San Francisco, used her informational website, The Preemie Primer, to criticize what she considered to be the March of Dimes' naivete in celebrating the approval of Makena before learning of its pricing.

Shortly after the drug's approval, Ther-Rx, the branded drug unit of KV Pharmaceutical Co., predicted health plans would cover the drug given the medical costs of preterm births, which some estimates peg at more than $50,000 in an infant's first year of life (Also see "KV Readies For End-Of-March Makena Launch" - Pink Sheet, 15 February, 2011.).

Payers Begin To Raise The Alarm

Nevertheless, Joanne Armstrong, a physician with Aetna's Women's Health Division in Sugar Land, Texas, said in a March 16 article published online by the New England Journal of Medicine that "this tremendous cost increase and the likely decrease in access to an effective medicine are sizable unintended consequences of the FDA approval of [Makena]. They demand reconsideration and corrective action."

Armstrong estimated the national cost of one course of treatment with Makena would be $4 billion, versus $41.7 million for compounded 17P, based on an estimated 139,000 women who could benefit from therapy and a cost of $29,000 for Makena.

Further, she suggested that for every dollar invested in compounded 17P, $8 to $12 in health care costs related to prematurity are saved, while in contrast, "Makena will require $8 to $12 in drug spending for every dollar in such prematurity costs avoided."

Sen. Sherrod Brown Labels Price "Exorbitant"

Sen. Sherrod Brown (D-Ohio) slammed the pricing in his own letter to the company, stating that the $1,500 per shot price tag was "exorbitant," and that Ther-Rx was "taking advantage of FDA approval at the expense of women, children, and federal and state budgets." A spokesman for Sen. Brown said that, as of March 15, he had not received a response from the company.

Patients have been among the most outspoken critics of Ther-Rx and KV, and to a lesser degree March of Dimes, which issued another statement March 14 in the form of a letter to the manufacturer saying that it was "deeply concerned that the cost of this lifesaving treatment could be put out of reach to thousands of women at risk for preterm delivery."

One patient group created a Facebook page specifically to shame the manufacturer.

Continued Compounding?

The University of Maryland's Harman, whose university clinic handles about 1,500 high-risk babies per year and whose referring hospitals deliver a total of about 9,000, said that he was concerned that local compounding pharmacists would not make the medication now that it is FDA-approved. "We're investigating our possibilities," he said.

The compounding pharmacies for now are striking a defiant pose. On March 14, the International Academy of Compounding Pharmacists issued a statement to patients and providers saying that, although many pharmacies had received a letter dated Feb. 17 from Ther-Rx advising that they could no longer compound an FDA-approved medication to which Ther-Rx had exclusive marketing rights, "In our estimation, the letter is nothing more than a 'scare tactic.' ... Pharmacists can legally compound FDA-approved products when a prescriber determines that the compounded preparation is more clinically appropriate for an individual patient."

David G. Miller, R.Ph., the group's chief executive, said in an email that the answer to the question of whether 17P can legally be compounded, in light of being an FDA-approved product with market exclusivity, was "clear and simple."

"If a prescriber determines that a compounded preparation of a medication is in the best clinical interest of his or her patient and discusses the available options with a pharmacist, there are no statutory or regulatory prohibitions on that professional decision," Miller said.

In its email, Ther-Rx said, "some have tried to equate drugs that have been compounded on an individualized basis by a pharmacy, such as 17P, with Makena. There are important differences, however, between an FDA-approved and regulated medication, and drugs that are often made by hand."

As an FDA-approved drug, "Makena is manufactured in an FDA-regulated and FDA-compliant sterile facility. The manufacturing process is tightly controlled to help ensure quality and consistency from dose to dose. This includes follow-up testing and reporting requirements that continue for the lifecycle of the medication," the company continued. "Makena is closely controlled by FDA regulations to monitor safety, efficacy and quality, and we have taken action to ensure that Makena will be available under the manufacturing agreements we have put into place. For all of these reasons, coverage and reimbursement are generally more straightforward with Makena, which helps remove barriers to access for families in need of this therapy."

But one criticism raised by Miller and others was that Makena had received FDA approval in part as a way to offer 17P with consistency across the market. However, Ther-Rx's parent company, KV Pharmaceutical Company, has recently faced legal trouble over active-ingredient inconsistencies and false labeling of other FDA-approved products. KV's former CEO pleaded guilty to breaching federal food and drug statutes by selling oversized morphine tablets (Also see "Former KV Pharmaceutical CEO Sentenced To 30 Days In Jail" - Pink Sheet, 10 March, 2011.).

[Editor's note: This story appears courtesy of Elsevier Global Medical News.]

- Jennie Smith (pinkeditor@elsevier.com), with additional reporting by Cathy Kelly (c.kelly@elsevier.com)

Makena Pricing Raises Ire Of Maternal Health Advocacy Groups

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