Makena Price Spike Causes Anger, Fear

How do you solve a problem like Makena?

In February, when the Missouri-based pharmaceutical firm Ther-Rx received from the Food and Drug Administration the exclusive right to market a progesterone injection formerly known as 17P, maternal-fetal health advocates cheered.

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 (N. Engl. J. Med. 2003;348:2379-85), the drug gained widespread use, even though practitioners had to order it from compounding pharmacies.

In February, the March of Dimes lauded the FDA’s decision to approve 17P under its orphan drug program, guaranteeing market exclusivity to Ther-Rx, which will market 17P as Makena. The March of Dimes praised the 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. This month, Ther-Rx revealed that each Makena shot would cost $1,500 – where it 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 offer the drug free to lower-income uninsured households, the full cost to insurers including Medicaid, according to an estimate provided by the American College of Obstetricians and Gynecologists, would be about $30,000 per pregnancy.

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."

"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," said Dr. Harman. 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," he said in an interview.

Ther-Rx did not answer calls seeking comment. On its Web site, 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."

Dr. Harman said he has been using 17P for about 5 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 United States.

"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 outrage 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 Web site, The Preemie Primer, to criticize what she considered to be March of Dimes’ naivete in celebrating the approval of Makena before learning of KV Pharmaceutical Company’s pricing intentions.

On March 11, three professional organizations, 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, a subsidiary of KV Pharmaceutical Company, critical of the pricing, stating that: "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."

Sen. Sherrod Brown (D-OH), 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.

Dr. Harman said the best people to pressure the FDA and government to reexamine the Makena decision were patients and the public. Last week, patients were among the most outspoken critics of Ther-Rx and KV Pharmaceutical Company, 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. Sarah Vandermeulen, age 30 years, of Paducah, Ky., was quick to join up. Ms. Vandermeulen said that in 2000, she had delivered a 1 lb 3oz baby at 23 weeks’ gestation who did not survive. In 2009, she became pregnant again and had heard about 17P from members of an online support group "I promptly asked my doctor if this was for me, and she agreed I may benefit from taking 17P," she said in an interview. Ms. Vandermeulen delivered a healthy baby at 37 weeks’ gestation.

"I obviously have no comparison or scientific data, but I do believe that 17P at the very least delayed preterm labor," said Ms. Vandermeulen. "I know that other women are scared for their current and future pregnancies. Many swear they wouldn’t have carried to term without 17P and are terrified that they will be denied this treatment option. I can tell you that there are discussions taking place on what we can do to help change the price increase."

The same question is also vexing clinicians. Dr. 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. "We may end up a producer ourselves," he said, adding that this was only "anxious conversation" in the near term.

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 warning letter dated Feb. 17 from Ther-Rx 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 e-mail that the answer to the question of whether 17P can legally be compounded, in light of 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," Mr. Miller said.

One criticism raised by Mr. Miller and others was that Makena had received FDA approval in part as a way to offer 17P with guaranteed 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 its FDA-approved products.

Just last week, KV Pharmaceutical Company’s former chief executive pleaded guilty to breaching federal food and drug statutes by selling oversized morphine tablets.

Dr. Harman said he had no relevant financial disclosures.

How do you solve a problem like Makena?

In February, when the Missouri-based pharmaceutical firm Ther-Rx received from the Food and Drug Administration the exclusive right to market a progesterone injection formerly known as 17P, maternal-fetal health advocates cheered.

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 (N. Engl. J. Med. 2003;348:2379-85), the drug gained widespread use, even though practitioners had to order it from compounding pharmacies.

In February, the March of Dimes lauded the FDA’s decision to approve 17P under its orphan drug program, guaranteeing market exclusivity to Ther-Rx, which will market 17P as Makena. The March of Dimes praised the 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. This month, Ther-Rx revealed that each Makena shot would cost $1,500 – where it 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 offer the drug free to lower-income uninsured households, the full cost to insurers including Medicaid, according to an estimate provided by the American College of Obstetricians and Gynecologists, would be about $30,000 per pregnancy.

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."

"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," said Dr. Harman. 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," he said in an interview.

Ther-Rx did not answer calls seeking comment. On its Web site, 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."

Dr. Harman said he has been using 17P for about 5 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 United States.

"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 outrage 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 Web site, The Preemie Primer, to criticize what she considered to be March of Dimes’ naivete in celebrating the approval of Makena before learning of KV Pharmaceutical Company’s pricing intentions.

On March 11, three professional organizations, 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, a subsidiary of KV Pharmaceutical Company, critical of the pricing, stating that: "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."

Sen. Sherrod Brown (D-OH), 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.

Dr. Harman said the best people to pressure the FDA and government to reexamine the Makena decision were patients and the public. Last week, patients were among the most outspoken critics of Ther-Rx and KV Pharmaceutical Company, 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. Sarah Vandermeulen, age 30 years, of Paducah, Ky., was quick to join up. Ms. Vandermeulen said that in 2000, she had delivered a 1 lb 3oz baby at 23 weeks’ gestation who did not survive. In 2009, she became pregnant again and had heard about 17P from members of an online support group "I promptly asked my doctor if this was for me, and she agreed I may benefit from taking 17P," she said in an interview. Ms. Vandermeulen delivered a healthy baby at 37 weeks’ gestation.

"I obviously have no comparison or scientific data, but I do believe that 17P at the very least delayed preterm labor," said Ms. Vandermeulen. "I know that other women are scared for their current and future pregnancies. Many swear they wouldn’t have carried to term without 17P and are terrified that they will be denied this treatment option. I can tell you that there are discussions taking place on what we can do to help change the price increase."

The same question is also vexing clinicians. Dr. 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. "We may end up a producer ourselves," he said, adding that this was only "anxious conversation" in the near term.

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 warning letter dated Feb. 17 from Ther-Rx 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 e-mail that the answer to the question of whether 17P can legally be compounded, in light of 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," Mr. Miller said.

One criticism raised by Mr. Miller and others was that Makena had received FDA approval in part as a way to offer 17P with guaranteed 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 its FDA-approved products.

Just last week, KV Pharmaceutical Company’s former chief executive pleaded guilty to breaching federal food and drug statutes by selling oversized morphine tablets.

Dr. Harman said he had no relevant financial disclosures.

How do you solve a problem like Makena?

In February, when the Missouri-based pharmaceutical firm Ther-Rx received from the Food and Drug Administration the exclusive right to market a progesterone injection formerly known as 17P, maternal-fetal health advocates cheered.

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 (N. Engl. J. Med. 2003;348:2379-85), the drug gained widespread use, even though practitioners had to order it from compounding pharmacies.

In February, the March of Dimes lauded the FDA’s decision to approve 17P under its orphan drug program, guaranteeing market exclusivity to Ther-Rx, which will market 17P as Makena. The March of Dimes praised the 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. This month, Ther-Rx revealed that each Makena shot would cost $1,500 – where it 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 offer the drug free to lower-income uninsured households, the full cost to insurers including Medicaid, according to an estimate provided by the American College of Obstetricians and Gynecologists, would be about $30,000 per pregnancy.

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."

"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," said Dr. Harman. 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," he said in an interview.

Ther-Rx did not answer calls seeking comment. On its Web site, 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."

Dr. Harman said he has been using 17P for about 5 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 United States.

"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 outrage 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 Web site, The Preemie Primer, to criticize what she considered to be March of Dimes’ naivete in celebrating the approval of Makena before learning of KV Pharmaceutical Company’s pricing intentions.

On March 11, three professional organizations, 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, a subsidiary of KV Pharmaceutical Company, critical of the pricing, stating that: "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."

Sen. Sherrod Brown (D-OH), 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.

Dr. Harman said the best people to pressure the FDA and government to reexamine the Makena decision were patients and the public. Last week, patients were among the most outspoken critics of Ther-Rx and KV Pharmaceutical Company, 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. Sarah Vandermeulen, age 30 years, of Paducah, Ky., was quick to join up. Ms. Vandermeulen said that in 2000, she had delivered a 1 lb 3oz baby at 23 weeks’ gestation who did not survive. In 2009, she became pregnant again and had heard about 17P from members of an online support group "I promptly asked my doctor if this was for me, and she agreed I may benefit from taking 17P," she said in an interview. Ms. Vandermeulen delivered a healthy baby at 37 weeks’ gestation.

"I obviously have no comparison or scientific data, but I do believe that 17P at the very least delayed preterm labor," said Ms. Vandermeulen. "I know that other women are scared for their current and future pregnancies. Many swear they wouldn’t have carried to term without 17P and are terrified that they will be denied this treatment option. I can tell you that there are discussions taking place on what we can do to help change the price increase."

The same question is also vexing clinicians. Dr. 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. "We may end up a producer ourselves," he said, adding that this was only "anxious conversation" in the near term.

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 warning letter dated Feb. 17 from Ther-Rx 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 e-mail that the answer to the question of whether 17P can legally be compounded, in light of 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," Mr. Miller said.

One criticism raised by Mr. Miller and others was that Makena had received FDA approval in part as a way to offer 17P with guaranteed 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 its FDA-approved products.

Just last week, KV Pharmaceutical Company’s former chief executive pleaded guilty to breaching federal food and drug statutes by selling oversized morphine tablets.

Dr. Harman said he had no relevant financial disclosures.