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A pedestrian walks past Biogen Inc.’s headquarters in Cambridge, Massachusetts, on Monday, June 7, 2021.

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The Food and Drug Administration’s independent advisory panel voted against the effectiveness of on Wednesday biogenic ALS drug under investigation for a rare and aggressive form of the disease.

The drug Tofersen was developed to treat a rare genetic form of amyotrophic lateral sclerosis, or ALS. Three advisers voted for effectiveness, five against, and one abstained.

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“Unfortunately, the presented study did not meet the primary and secondary endpoints,” said Dr. Liana Apostolova, a professor of neurology at Indiana University School of Medicine, who voted against Tofersen’s effectiveness.

However, the panel unanimously agreed that the drug could have clinical benefit by reducing a protein linked to the severity of the disease.

Michelle Mielke, a professor of epidemiology at Wake Forest University School of Medicine who voted for the drug, acknowledged the data is not entirely conclusive, but said, “There are several aspects of the data that point to strong clinical evidence .”

“And again, my decision also took into account the fact that there really is an unmet need,” she added.

Expedited approval is an FDA designation that approves drugs faster when they meet an unmet medical need for a serious medical condition. Such approval would require Biogen to further study the drug to confirm its clinical utility.

The FDA generally follows the advice of its advisory committees, but is not required to do so. A final decision will be made on April 25th.

ALS, most commonly known as Lou Gehrig’s disease, is a progressive and fatal neuromuscular disease that causes nerve cells in the brain and spinal cord to deteriorate over time, causing people to lose muscle control, they need to move, talk, breathe and eat. The disease eventually leads to paralysis and even death, and generally affects people between the ages of 40 and 70.

The drug targets a form of ALS in people with mutations in a specific gene that is passed down through generations within families. These mutations can cause a protein called SOD1 to build up to toxic levels, which can ultimately damage the nervous system and lead to the development of ALS.

According to Biogen, only a few thousand people worldwide have been diagnosed with this SOD1 mutation, or about 2% of the 168,000 people who have ALS worldwide. In the US, that number is even lower, with about 330 people affected by the SOD1 mutation. The median survival time from diagnosis with the rare form of ALS to death is 2.7 years, according to the company.

The SOD1 mutation is associated with 20% of cases occurring within families.

Families affected by ALS are hoping the drug could pave the way for more research to tackle the disease’s cause, potentially leading to new treatments for the estimated 5,000 new people in the US diagnosed with ALS each year. Globally, researchers at the National Institutes of Health expect ALS cases to increase by almost 70% to approximately 376,000.

Review of mixed efficacy data

The FDA accepted Biogen’s application for full approval of Tofersen in July. In October, the agency extended the review of the application by three months.

The advisory panel relied on controversial data from a phase III clinical trial of Tofersen. The drug failed to slow the progression of ALS in this study, but both Biogen and FDA staff noted the potential limitations of the study. The duration of the study was 28 weeks, which may not have been enough time to observe the effect of Tofersen on disease progression.

The panel focused on evaluating Tofersen’s effect on key proteins associated with the development of ALS. According to an FDA review of the company’s data, the SOD1 protein levels of patients in the study who received Tofersen decreased by 26% to 38% compared to those who received placebo.

But the panel specifically focused on the drug’s effect on another key protein called neurofilament light, or NfL. High levels of the protein are found in a variety of neurological conditions, such as ALS, and are linked to disease severity and progression in patients, according to the FDA review.

Biogen’s phase 3 study found that people who received Tofersen experienced a 55 percent reduction in NfL levels by week 28 of the study, compared with an average increase of 12 percent for people who received placebo. An ongoing study of Tofersen had similar results: People who received the drug in the phase 3 study maintained their lowered NfL levels over time.

Those who received a placebo during the phase 3 study but switched to Tofersen in the extension study saw a 44% drop in NfL levels, the FDA review added.

In a unanimous vote, the panel said Tofersen’s reduction in NfL likely predicts the drug’s clinical utility in people with SOD1-ALS.

“It appears that NFL is bad for neurons and is associated with neuronal death, so if it’s lower then neuronal death should be lower,” said Dr. David Weisman, Director of the ANA Clinical Research Center.

The FDA staffers, who presented their review of Biogen’s data ahead of the panel vote, also said these “convincing reductions” in NfL are expected to result in a slower decline in patients.

The panel also considered Tofersen’s safety data. In the phase 3 study, the most common adverse events associated with the drug were pain in the joints and muscles, and fatigue.

According to the FDA review, about 18% of people who received Tofersen experienced serious adverse events compared to 14% of people who received the placebo. However, FDA staff noted that many of the reported events are related to “underlying disease progression” and not to Tofersen use. None of the adverse events were fatal.

Public Requests for Consent

During public comments, Alison Burell said her family believes Tofersen significantly slowed the progression of the disease in her husband Cory, who died from the rare form of ALS in 2019. He participated in Biogen’s early clinical trial on Tofersen and continued taking the drug after the trial was completed, which Burell believes extended his life by another six months.

“Tofersen gave Cory time with his boys, made memories and showed them that they never give up,” Burrell said. “I ask that you commend your agreement to support Tofersen. Please give hope to others with SOD1.”

Cassandra Haddad also asked the panel to recommend approval, noting that her family has a SOD1-ALS “body count” of 33. She said her late mother was the youngest member to be diagnosed with the rare form of the disease, but took Tofersen to extend her life by several months and “gave us this precious time together.”

“It’s a miracle, the miracle of having access to a drug that specifically targets our genetic mutation and extends our lives,” Haddad said. She added that she herself participated in Biogen’s ongoing Tofersen study called ATLAS and is being monitored for ALS symptoms.

“We all know that early intervention leads to better outcomes. Without Tofersen, I have no chance of survival and no hope,” Haddad said, adding, “Today, you have the power to help me and the legacy of my family’s death.”

Further research on Tofersen ahead

Biogen outlined its plans to review Tofersen’s benefits if the drug receives accelerated FDA approval. The company will collect data from ATLAS, which aims to study whether the drug can help delay the onset of ALS in patients with the SOD1 mutation.

The study started in 2021 and includes 150 participants, which is nearly 50% of the SOD1-ALS population to date, Biogen said. The Company also plans to continue evaluating data from the ongoing extension of the Phase 3 clinical trial, which is expected to conclude in 2024.

“Biogen is committed to confirming the clinical utility of Tofersen in SOD1-ALS as soon as possible,” said Stephanie Fradette, Biogen’s director of clinical development and leader of the ALS portfolio.

Correction: FDA advisors voted against Tofersen’s effectiveness. A previous version of this story misrepresented the exact nature of this vote.

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Moderna CEO Stephane Bancel testifies before the Senate Health Committee Wednesday about the pricing of the company’s Covid-19 vaccine.

The Boston-based biotech plans to charge $130 per dose once the vaccination program moves to the private market as early as this fall. Sen. Bernie Sanders, I-Vt., Chair of the Health Committee, hit out Modern in a letter to Bancel in January, in which he called the price increase “outrageous”.

Join us for CNBC’s Healthy Returns on March 29, where we’re hosting a virtual gathering of healthcare CEOs, scientists, investors and innovators to reflect on the advances made today in reinventing the future of medicine. We also have an exclusive look at the best investment opportunities in biopharma, healthcare technology and managed care. Learn more and register today: http://bit.ly/3DUNbRo

After Sanders sent the letter, Moderna said it would create a utility to keep the vaccine free for people who are uninsured or underinsured.

People who have Medicare, Medicaid, or private insurance should still get the shot for free, but Sanders said the price hike “will cost taxpayers billions of dollars.”

A fungus that is often resistant to drugs has been spreading at an “alarming rate” in healthcare facilities across the United States, according to the Centers for Disease Control and Prevention.

Candida auris is an emerging fungus that is serious and potentially fatal for hospital patients, particularly those with multiple medical conditions.

The fungus was first identified in Asia in 2009, and the first case in the US dates back to 2013. Candida auris was limited to New York City and Chicago, but has since been detected in more than half of U.S. states and has become endemic in some areas, according to a CDC report published Monday in the Annals of Internal Medicine.

From 2019 to 2021, 17 states detected their first-ever cases of the fungus. California, the Mid-Atlantic region, the Midwest, Texas and Florida all had increased transmission during this time, according to the CDC.

Infections have increased by about 200% from about 500 infections in 2019 to more than 1,400 in 2021. The fungus has spread most strongly in long-term hospitals for people with serious illnesses who require ongoing treatment, according to the CDC.

Symptoms can vary widely depending on the type of infection, but fever and chills are the most common. People with weakened immune systems, diabetics who take many antibiotics, or who have breathing tubes, feeding tubes, and catheters are more likely to be affected.

A 2021 CDC report found that two outbreaks of the fungus, which was resistant to echinocandin, had a 30% mortality rate over 30 days. The cases studied in the outbreaks were mostly critically ill patients in long-term care facilities, so the exact contribution of Candida auris to the deaths was unclear. The outbreaks occurred in Washington, DC and Texas.

Join us for CNBC’s Healthy Returns on March 29, where we’re hosting a virtual gathering of healthcare CEOs, scientists, investors and innovators to reflect on the advances made today in reinventing the future of medicine. We also have an exclusive look at the best investment opportunities in biopharma, healthcare technology and managed care. Learn more and register today: http://bit.ly/3DUNbRo

Candida auris is often resistant to drugs used to treat fungal infections. In 2020, 86% of samples were resistant to a class of antifungal drugs called azoles, and 26% were resistant to amphotericin B, according to the CDC.

Just over 1% of samples tested in 2020 were strains resistant to the main class of drugs used to treat such infections, called echinocandins, up from 0.4% in 2018. The CDC said that although resistance to Echinocandin is still uncommon, the number of such cases increasing in 2021 has tripled compared to the previous two years.

“Even this subtle increase is concerning because echinocandins are the first-line therapy for invasive candida infections and most cauris infections,” the CDC said in its report.

The CDC attributed the rapid spread of the fungus to a decline in infection control during the pandemic due to strains on the healthcare system, from staffing and equipment shortages to an increase in patient burden and increased use of antibiotics.

“The rapid rise and geographic spread of cases is worrying and underscores the need for continuous surveillance, expanded laboratory capacity, faster diagnostic testing, and adherence to proven infection prevention and control practices,” said CDC epidemiologist Dr. Meghan Lyman, the report’s lead author.