Why This FDA-Approved Drug for Pre-Term Birth is being Pulled From the Market

The US Food and Drug Administration (FDA) announced recently that Makena, a drug that has been approved since 2011 to prevent preterm birth, will be withdrawn from the market. The decision has sparked concern and confusion among patients, doctors, and advocates who have been pushing for a solution to the high rate of premature births in the US.

Makena, whose active ingredient is hydroxyprogesterone caproate (17P), was approved for use in women who had a history of delivering babies prematurely. The drug was expected to reduce the risk of preterm birth in subsequent pregnancies by as much as 33%. It was also recommended for women who were pregnant with twins or other multiples.

However, recent clinical trials and evidence have shown that Makena did not provide a significant benefit in preventing preterm birth compared to the placebo group. In fact, some studies even suggest that Makena may increase the risk of certain adverse effects, such as miscarriage or stillbirth.

This decision to withdraw Makena from the market has opened a debate on the effectiveness of the FDA’s drug approval process and the role of pharmaceutical companies in clinical research. It has also raised concerns regarding the availability of effective treatments for women who are at risk of preterm birth, an issue that affects nearly one in ten births in the US.

What is Pre-Term Birth?

Pre-term birth, also known as premature birth, is when a baby is born before 37 weeks of gestation, according to the World Health Organization (WHO). In the United States, the March of Dimes estimates that about 1 in 10 babies is born prematurely. Pre-term birth can lead to a number of health risks for the baby, including respiratory distress syndrome, jaundice, and an increased risk for long-term health problems such as cerebral palsy and developmental delays.

Pre-term birth can be caused by a variety of factors, including health conditions of the mother such as infections or high blood pressure, issues with the placenta, or lifestyle factors such as smoking or using drugs. In some cases, however, the cause of pre-term birth is unknown.

Treatment for pre-term birth may include medications to slow down or stop labor, medication to help the baby’s lungs mature before birth, or other interventions depending on the specific circumstances of the pregnancy.

It is important for pregnant individuals to receive proper prenatal care to reduce their risk of pre-term birth, and to speak with their healthcare provider if they experience any symptoms of pre-term labor, such as contractions or vaginal bleeding.

The FDA-Approved Drug

What is the FDA-approved drug for pre-term birth?

The FDA-approved drug for pre-term birth is Makena, which is made up of the hormone progesterone.

Why was it approved by the FDA?

Makena was approved by the FDA to reduce the risk of pre-term birth in women who had previously given birth prematurely.

Pre-term birth is a major health concern that can lead to a range of long-term health complications for both mothers and babies.

Makena was considered a breakthrough drug for the prevention of pre-term birth, as it was the first and only FDA-approved treatment for this condition.

How was Makena administered?

Makena was administered to patients as weekly injections starting at 16-20 weeks of pregnancy, throughout the duration of the pregnancy.

The drug was indicated for use in women who had a history of pre-term birth, which put them at increased risk of delivering prematurely in subsequent pregnancies.

Why is Makena being pulled from the market?

Makena is being pulled from the market due to a study that found the drug did not significantly reduce the risk of pre-term birth in women with a history of pre-term delivery.

The FDA determined that the drug’s benefits did not outweigh its risks, and that it should be removed from the market due to concerns about its efficacy.

However, the decision to pull the drug has been controversial, as many women’s health advocates argue that Makena still has some benefit in preventing pre-term birth, and that it should remain available to patients who may benefit from its use.

The Side Effects of the Drug

Risk of Cardiovascular Events

One of the most concerning side effects of this drug is its potential to increase the risk of cardiovascular events in pregnant women. A clinical trial conducted by the manufacturer of the drug found that women taking the drug had a higher risk of blood clots, heart attacks, and other cardiovascular events compared to those taking a placebo.

This risk is particularly alarming in pregnant women, as they are already at an increased risk of cardiovascular complications due to the demands of pregnancy on their bodies.

Increased Risk of Infection

Another potential side effect of this drug is an increased risk of infection in both the mother and baby. The drug suppresses the immune system, which can make it more difficult for the body to fight off infections.

This is especially concerning for premature infants, who are already at an increased risk of infections due to their underdeveloped immune systems.

Other Side Effects

In addition to the above, the drug has also been associated with other side effects such as nausea, vomiting, dizziness, headaches, and vaginal bleeding. While these side effects may not seem as serious as the cardiovascular and infection risks, they can still be very uncomfortable and potentially harmful to the patient.

It is important for healthcare providers to carefully weigh the risks and benefits of any medication they prescribe, particularly when it comes to pregnant women and infants.

Comparison of Risks and Benefits

	Benefits	Risks
Drug	Reduces risk of preterm birth	Increased risk of cardiovascular events, infection, and other side effects
Alternative	No known benefits	No known risks

This table illustrates the difficult decision faced by healthcare providers when deciding whether to prescribe this drug or seek an alternative. While the drug has been shown to reduce the risk of preterm birth, the potential risks must also be taken into account.

The Clinical Trials

Phase III Trials

In 2011, the FDA approved the use of Makena based on the results of two Phase III clinical trials. These trials involved over 1,700 women and showed that Makena reduced the risk of preterm birth by 33% in women who had previously given birth prematurely.

The trials were double-blind, randomized, and placebo-controlled. The participants were given either Makena or a placebo weekly between 16 and 36 weeks of pregnancy. The trials also monitored potential adverse reactions, and no serious adverse reactions were observed.

Post-Approval Studies

As part of the approval process, the FDA required that the drug’s manufacturer, AMAG Pharmaceuticals, conduct post-approval studies to further evaluate the drug’s safety and efficacy in the real-world setting.

However, these studies failed to confirm the results of the Phase III trials. A study conducted by the Eunice Kennedy Shriver National Institute of Child Health and Human Development found no significant difference in preterm birth rates between women who received Makena and those who did not.

Another study conducted by AMAG Pharmaceuticals showed a reduction in preterm birth rates, but the reduction was not as significant as in the Phase III trials. These findings raised concerns about the drug’s effectiveness, leading to the decision to remove it from the market.

The Drug’s Manufacturer

Manufacturer Background

The drug in question, Makena, is manufactured by AMAG Pharmaceuticals, a biopharmaceutical company headquartered in Waltham, Massachusetts. AMAG Pharmaceuticals focuses on developing therapeutics for maternal health, anemia, and cancer supportive care.

Approval and Market Performance

Makena, which is a synthetic form of the hormone progesterone, was initially approved by the FDA in 2011 for reducing the risk of preterm birth in women who had previously experienced preterm birth. The drug was a significant commercial success, with sales reaching over $500 million in 2018.

Controversies and Legal Troubles

However, the drug has also faced controversies and legal battles. In 2019, AMAG Pharmaceuticals was subject to a lawsuit from the FDA for promoting Makena off-label and thus violating FDA regulations. In addition, the efficacy of Makena has also been called into question, with some studies indicating that the drug may not be superior to a placebo.

Impact on AMAG Pharmaceuticals

The FDA’s decision to withdraw the approval of Makena is a significant blow to AMAG Pharmaceuticals. The company has already been struggling financially, and the loss of its primary revenue source will likely have a significant impact. In response, AMAG Pharmaceuticals has announced that it will explore strategic options, including divesting itself of Makena and other non-core assets.

The FDA’s Actions

Initial Approval and Monitoring

In 2011, the FDA approved Makena, a drug used to prevent pre-term birth in pregnant women at high risk. However, the approval came with the condition that the drug’s manufacturer, AMAG Pharmaceuticals, conduct a post-market study to confirm the drug’s effectiveness.

The FDA also required AMAG to submit regular reports on Makena’s safety and efficacy. Initially, the drug seemed to be working as intended. Pregnant women receiving the drug had fewer premature births, and no major safety concerns were reported.

Recent FDA Decision

However, in early 2020, the FDA announced that it was requesting Makena’s removal from the market. The FDA cited the results of the post-market study, which showed that Makena did not significantly reduce pre-term birth rates compared to a placebo.

The FDA also stated that ongoing monitoring had not identified any new safety concerns with the drug. However, the agency concluded that Makena’s lack of effectiveness meant that it no longer met the standards necessary for FDA approval.

Impact on Patients

The FDA’s decision to remove Makena from the market has been controversial. Some patient advocacy groups have expressed concern that the drug’s removal could leave pregnant women without effective treatment options.

However, the FDA has pointed out that there are other treatments available for pre-term birth, and that doctors can still prescribe Makena “off-label” if they choose to do so. The agency has also noted that AMAG can continue to conduct research on the drug’s effectiveness, and that the FDA may reconsider its decision if new data emerges showing that Makena is safe and effective.

The Reason for the Drug’s Withdrawal

The FDA-approved drug for pre-term birth, Makena, is being pulled from the market due to its lack of effectiveness in preventing preterm delivery. According to a clinical trial, the drug did not reduce the incidence of preterm birth compared to a placebo.

Despite being approved by the FDA in 2011 under the accelerated approval pathway, Makena was required to conduct a confirmatory clinical trial to verify its clinical benefit. The trial, known as the PROLONG study, was conducted by AMAG Pharmaceuticals, the manufacturer of Makena.

The PROLONG Study Results

The PROLONG study was designed to evaluate the efficacy of Makena in reducing the incidence of preterm birth among pregnant women with a history of spontaneous preterm delivery. The study enrolled 1,719 women and randomized them to receive either Makena or a placebo.

The results of the study showed that there was no significant difference in the rate of preterm birth between the Makena and placebo groups. The preterm birth rate was 11.1% in the Makena group and 11.4% in the placebo group.

Based on these findings, the FDA has determined that the drug’s benefits do not outweigh its risks and has recommended its withdrawal from the market.

Impact on Pregnant Women

The withdrawal of Makena from the market may have an impact on pregnant women at risk of preterm delivery. Healthcare providers may need to consider alternative treatment options for their patients.

However, it is important to note that Makena is not the only treatment option for preterm birth. There are other FDA-approved drugs, as well as non-pharmacologic interventions, that may be considered for pregnant women at risk of preterm delivery.

The FDA’s decision to withdraw Makena from the market underscores the importance of conducting rigorous clinical trials to ensure the safety and efficacy of drugs, especially those approved under accelerated pathways.

What Does This Mean for Patients?

Alternative treatment options

Patients who have been relying on Makena for preventing pre-term birth may now have to turn to alternative treatment options. This could mean taking a different drug or using non-pharmaceutical methods to manage their condition. It is important for patients to work with their healthcare provider to determine the best course of action.

Cost implications

Patients who were receiving Makena through insurance may face higher costs for alternative treatment options. This is because insurance may not cover the full cost of other drugs or non-pharmaceutical methods. It is important for patients to review their insurance coverage and explore financial assistance programs that may be available.

Impact on pregnancies

Patients who have been taking Makena during their pregnancy may wonder if it will have any impact on their current or future pregnancies. The FDA has stated that they do not believe the drug poses any immediate harm to patients who have already received it. However, patients should still discuss any concerns with their healthcare provider.

Future drug development

The removal of Makena from the market may prompt further research and development of new drugs for preventing pre-term birth. Patients and healthcare providers should stay informed of any new developments in this area and discuss the best treatment options for individual patients.

The Impact on the Medical Community

Preventing Preterm Birth

The withdrawal of the FDA-approved drug for preterm birth will have a significant impact on the medical community. Preterm birth is a leading cause of infant mortality and morbidity globally and in the United States. The drug was effective in delaying preterm birth and reducing the risks associated with preterm delivery. Without this drug, doctors will have limited options to manage women at high risk of preterm delivery.

Research and Development

The withdrawal of the drug highlights the pressing need for more research and development of effective therapies for preterm birth. The medical community needs to continue to prioritize the development of safe and effective agents for managing preterm birth. The withdrawal of the drug also emphasizes the importance of long-term safety studies for drugs approved through the accelerated approval process.

Patient Safety

The withdrawal of the drug raises concerns about patient safety. Women who were receiving the drug will need to be evaluated for alternative treatments and monitored for any adverse effects related to the discontinuation of this drug. The medical community needs to ensure that patient safety is prioritized in the management of preterm birth, despite the difficulties in finding safe and effective treatments.

Communication and Education

The impact of the withdrawal of the drug also highlights the importance of communication and education within the medical community. Physicians need to be aware of the latest research and guidelines for managing preterm birth and be able to communicate these findings effectively with their patients. The medical community needs to work together to ensure that patients are informed about the risks and benefits of all treatments for preterm birth, including those that are no longer available on the market. Overall, the withdrawal of the drug is a reminder that the medical community needs to continue to work together to develop safe and effective treatments for preterm birth and ensure patient safety.

The Response from Advocacy Groups

March of Dimes

The March of Dimes, a nonprofit organization dedicated to improving the health of mothers and babies, expressed disappointment in the decision to remove Makena from the market. In a statement, the organization called for continued access to the drug and stated that “pregnant people and their healthcare providers need access to safe and effective treatments for preterm birth.”

American College of Obstetricians and Gynecologists

The American College of Obstetricians and Gynecologists (ACOG) also spoke out against the decision to remove Makena from the market. In a statement, the organization expressed concern that the removal of the drug would leave patients with limited options for preventing preterm birth.

ACOG recommended that the FDA work with the drug’s manufacturer to gather more data on the drug’s safety and effectiveness, rather than completely removing it from the market.

National Perinatal Association

The National Perinatal Association, a professional organization dedicated to improving perinatal health, called for increased investment in research for preterm birth treatments. In a statement, the organization expressed concern that the removal of Makena would leave pregnant patients with limited options for preventing preterm birth.

The organization also urged the FDA to work with the drug’s manufacturer to develop better strategies for identifying patients who would benefit most from the drug.

The National Perinatal Association emphasized the importance of finding safe and effective treatments for preterm birth, which has significant health consequences for both mothers and babies.

The Response from the Drug’s Manufacturer

Statement from AMAG Pharmaceuticals

AMAG Pharmaceuticals, the manufacturer of Makena, released a statement in response to the FDA’s decision to withdraw its approval of the drug. The company expressed disappointment in the decision, stating that it believes in the safety and effectiveness of Makena.

AMAG also emphasized its commitment to women’s health and the prevention of preterm births, pointing to its support of programs and initiatives aimed at addressing the issue. The company has vowed to work closely with the FDA to address concerns and explore options for keeping Makena available for patients who depend on it.

Planned Actions

AMAG has announced that it plans to convene a meeting of its board of directors and seek input from its stakeholders and medical experts to discuss the best course of action in response to the FDA’s decision. The company has also indicated that it will continue to market and sell Makena until the withdrawal of approval becomes effective, which is expected to occur in February 2021.

AMAG has also stated that it will take steps to ensure that patients currently using Makena are provided with information about alternative treatments for preterm birth. The company has created a website, makename.com, which provides resources for patients and healthcare providers related to preterm birth and treatment options.

• AMAG has expressed its intent to appeal the FDA’s decision and explore additional data and evidence that could support Makena’s safety and effectiveness.
• The company has also stated its commitment to ongoing research and development efforts aimed at addressing preterm birth and improving outcomes for mothers and babies.

The Response from the FDA

Initial Statement

In their initial statement regarding the removal of Makena from the market, the FDA expressed concern over the lack of evidence supporting the drug’s effectiveness. They stated that the required post-market study did not demonstrate a significant clinical benefit of Makena in reducing the risk of preterm birth.

Request for Withdrawal

After considering the results of the post-market study, the FDA requested that AMAG Pharmaceuticals voluntarily withdraw Makena from the market. They stated that without sufficient evidence of the drug’s effectiveness, they could not continue to allow it to be sold to patients.

Continuing Review

The FDA continues to review the safety and effectiveness of other treatments for preterm birth, and encourages further clinical research in this area. They acknowledge the importance of finding effective treatments for this serious health issue, but emphasize the need for rigorous scientific evidence to support any drug’s approval and use.

Impact on Patients

The FDA understands that the withdrawal of Makena from the market may have a significant impact on patients and healthcare providers. They have provided guidance for healthcare professionals on alternative treatment options and encourage patients to discuss any concerns with their healthcare providers.

• Source: FDA

The Future of Pre-Term Birth Treatment

Advancements in Research

Researchers are constantly working to find new and better treatments for pre-term birth. One promising area of research is the use of progesterone to prevent pre-term labor. Ongoing clinical trials are exploring the use of different forms of progesterone, such as injections and vaginal suppositories, to prolong pregnancy and reduce the risk of pre-term birth. Other studies are focusing on the use of medications that target specific hormones or inflammatory pathways that can lead to pre-term labor.

Personalized Medicine

In the future, pre-term birth treatment may become more personalized based on a woman’s individual risk factors and medical history. Researchers are exploring the use of genetic testing to identify women at increased risk for pre-term birth, and then tailoring treatment based on their individual needs. This could include the use of specific medications or therapies that are more effective for certain types of pre-term labor.

Collaborative Care

Preventing pre-term birth often requires a team approach, with obstetricians, neonatologists, and other healthcare providers working together to provide the best care for mother and baby. In the future, we may see more collaborative care models that involve a range of healthcare providers, including nurses, midwives, and social workers. This could help ensure that women at risk for pre-term birth receive comprehensive care that addresses their physical, emotional, and social needs.

Conclusion

While pre-term birth is a serious medical problem, there is hope for the future. With advancements in research, personalized medicine, and collaborative care, we may be able to greatly reduce the number of pre-term births and improve outcomes for both mothers and babies. It is important for women to work closely with their healthcare providers to understand their individual risks for pre-term birth and to take steps to prevent it when possible.

The Importance of Clinical Trials

Effective Drug Development

Clinical trials are essential for the development of safe and effective drugs. They provide the necessary scientific evidence to determine whether a new drug is effective, how it compares to current treatments, and any potential side effects or risks it may have. Without clinical trials, it would be impossible to determine the safety and efficacy of new treatments and medications.

Protecting Patient Safety

Patient safety is a top priority in clinical trials. Before a new drug is tested on human subjects, it undergoes rigorous pre-clinical testing to ensure it is safe for clinical trials. During the clinical trial process, participants are closely monitored for any adverse reactions or negative side effects. If a participant experiences any unexpected side effects, the trial may be halted to ensure patient safety.

Advancing Medical Knowledge

Clinical trials not only advance medical treatments but also help to advance medical knowledge. By participating in a clinical trial, patients can contribute to the understanding of a disease and its treatment options. Additionally, clinical trials provide opportunities for researchers to develop new hypotheses and test new treatment strategies.

Ensuring Regulatory Approval

Clinical trials are a necessary step in the regulatory approval process. The findings from clinical trials are utilized by regulatory agencies such as the FDA to determine whether a drug is safe and effective and should be approved for use in the general population. Without clinical trials, regulatory agencies would not have the necessary data to make informed decisions about drug safety and efficacy.

Conclusion

Clinical trials play a critical role in the development of new drugs and treatments. They ensure patient safety, advance medical knowledge, and ultimately lead to the approval of safe and effective treatments. As such, it is important for patients and medical professionals to support and participate in clinical trials.

The Role of the FDA

Regulation of Drugs

The Food and Drug Administration (FDA) is responsible for regulating drugs in the United States. It evaluates the safety and efficacy of drugs before allowing them to be marketed and sold. The FDA also monitors drugs after they have been approved to ensure that they remain safe and effective.

Approval Process

The FDA’s approval process for drugs is rigorous and can take several years. Drug manufacturers must demonstrate through clinical trials that their drugs are safe and effective for the intended use. The FDA reviews the data from these trials and decides whether to approve the drug for sale.

Drug Recalls and Withdrawals

Despite the rigorous approval process, sometimes drugs can have adverse effects that were not detected during the clinical trials. When the FDA becomes aware of safety concerns related to a drug, it can issue a recall or require the drug manufacturer to withdraw the drug from the market. The FDA takes these actions to protect the health and safety of consumers.

Impact on Healthcare

The FDA’s role in regulating drugs has a significant impact on healthcare in the United States. It ensures that drugs are safe and effective for the intended use and helps to prevent harm to patients. The approval process can sometimes be lengthy and expensive for drug manufacturers, but it also provides assurance to healthcare providers and patients that the drugs they are using have been thoroughly tested and evaluated.

The Role of Patients and Advocacy Groups

Advocacy groups play a critical role in advocating for patient safety and access to medications

Advocacy groups are instrumental in keeping patients informed about changes in the healthcare industry. In the case of the FDA-approved drug for pre-term birth that is being pulled from the market, advocacy groups have been working tirelessly to communicate the risks and benefits of the medication to patients and healthcare providers. They are also advocating for alternative treatments to be made available to patients in need.

Patient advocacy groups empower patients to make informed decisions about their healthcare

Patient advocacy groups provide support and resources to patients who are navigating complex healthcare systems. They empower patients to be active participants in their own healthcare by providing them with information about their conditions, treatment options, and rights. Patient advocacy groups are also a powerful voice in pushing for policies that improve access to healthcare and ensure that patients are able to receive the care they need.

• Advocacy groups can offer guidance and support to patients who have been impacted by the recall of the FDA-approved drug for pre-term birth
• Patient advocacy groups are working to ensure that patients have access to alternative treatments and that they are informed about the risks associated with the recalled medication
• Advocacy groups are also pushing for changes in the healthcare system that prioritize patient safety and access to care

Patient feedback and involvement is essential in shaping healthcare policies

Patients have a unique perspective on the healthcare system, and their feedback and involvement is crucial in shaping policies that impact their lives. Patient advocacy groups can work with patients to gather feedback on their experiences with healthcare providers, medications, and treatments. This feedback can be used to inform policy decisions and improve the quality of care that patients receive. By working together, patients, advocacy groups, and healthcare providers can create a healthcare system that prioritizes patient safety and access to care.

The Final Verdict

The FDA’s decision

The FDA’s decision to withdraw Makena from the market has been met with mixed reactions. While some believe that the agency made the right call, others believe that it was a hasty decision that will harm women and their babies.

The FDA stated that recent data failed to prove that Makena was effective in preventing preterm birth in women with a history of the condition. As such, the agency concluded that the risks and benefits of the drug were no longer favorable and that it should be removed from the market.

The impact on preterm birth prevention

The withdrawal of Makena is a setback for preterm birth prevention efforts. The drug was the only FDA-approved treatment for preventing preterm birth in women with a history of the condition. As such, its absence leaves a void that will be difficult to fill.

However, there are other interventions that can be used to reduce preterm birth rates, such as progesterone injections and lifestyle modifications. While these interventions may not be as effective as Makena, they can still make a difference in preventing preterm birth and improving neonatal outcomes.

The future of preterm birth prevention

The withdrawal of Makena highlights the need for more research into preterm birth prevention strategies. There is a pressing need to identify new drugs and interventions that can effectively reduce preterm birth rates and improve neonatal outcomes.

In the meantime, healthcare providers will need to rely on alternative interventions and closely monitor their patients for signs of preterm labor. This will require a multi-disciplinary approach that involves obstetricians, neonatologists, and other healthcare professionals working together to prevent preterm birth and mitigate its consequences.

The Long-Term Impact

Effects on Premature Birth Prevention

The withdrawal of the FDA-approved drug for pre-term birth prevention will have a significant impact on the prevention of premature births. The drug was proven to be effective in reducing the risk of premature birth in women at high risk of delivering early. Without this drug, medical professionals will need to explore alternative treatments and prevention methods that may not be as effective.

Impact on Maternal and Fetal Health

The withdrawal of this drug from the market will also impact the health of pregnant women and their fetuses. Women who are at high risk of pre-term delivery will no longer have access to a proven preventative measure, which could result in negative health outcomes for both mother and child. The lack of effective preventative measures could also result in an increase in medical interventions, such as inductions and Cesarean deliveries, which carry their own risks.

Economic Consequences

The withdrawal of this drug from the market may also have significant economic consequences. The costs associated with premature birth, such as extended hospital stays, follow-up care, and long-term health complications, are substantial. The use of this medication may have reduced these costs over time by preventing premature births. Without this preventative measure, healthcare costs may increase, putting a strain on individuals, families, and healthcare systems.