Stevens Nation Responds to FDA's Refusal to File Letter, NurOwn Recipients Call for Advisory Committee Meeting

FDA Decision Does Not Adhere to Administration's Own Guidance and Ignores Evidence of NurOwn's Effectiveness

Advisory Committee Meeting is Needed to Allow Patient Voices to be Heard and to Provide Transparent Consideration of NurOwn's Impact

WASHINGTON, Nov. 21, 2022 /PRNewswire/ -- Brainstorm Cell Therapeutics is seeking FDA approval of its mesenchymal stem cell therapy called NurOwn for the treatment of ALS. In response to the FDA's Refusal to File letter, and as people who participated in the NurOwn trials and its Expanded Access program ("EAP"), we support Brainstorm's efforts to seek an Advisory Committee ("AdCom") meeting.

We believe the FDA's position ignores the vast evidence of efficacy and denies both the company's and patients' rights of due process. Further, we believe that the letter does not adhere to FDA's own guidance. An AdCom will allow the full array of data to be examined and will give voice to trial participants, the drug sponsor, investigating neurologists and treating clinicians. We must insist that the FDA allow testimony about the "clinically meaningful" changes that occurred when we received NurOwn.

In its quarterly call, Brainstorm outlined the FDA's position in the Refusal to File letter. The FDA concluded there is not "substantial evidence" of efficacy because the Phase III study did not meet its primary endpoint. However, the Phase III trial did meet a pre-specified secondary endpoint in a subgroup of patients with less advanced ALS.

For over five years, the ALS community fought for the adoption of an FDA Guidance Document for ALS, which was implemented in 2019. It provides that evidence of a treatment effect can be assessed by "less decline, stabilization or improvement" in function. Further, objective findings of "even of a small magnitude" can demonstrate efficacy.

Two of the most critical commitments made in that Guidance Document were: (1) the FDA's willingness to "exercise regulatory flexibility" for the "critical unmet need" in ALS; and (2) the willingness to consider "patient reported outcomes" as evidence of efficacy.

The FDA evaluates whether substantial evidence of efficacy exists by asking whether a therapy provides a "clinically meaningful" impact. In essence, how does a therapy make a person "feel and function?" The best people to attest to how NurOwn made them "feel and function" are the people who received NurOwn. Indeed, in a patient listening session in 2019 with the leadership of CDER and CBER, the FDA promised the ALS community: "if it helps you function, and you can prove it, we'll approve it!"

We are asking the FDA to let us prove it.

After receiving NurOwn, each of us halted our ALS decline and improved in some areas of function. The following are some of our changes in daily activities that prove NurOwn works.

• walk without a walker, walk longer distances, walk in sand or farm field
• rise out of a chair unassisted and get up off the floor unassisted
• climb up and down stairs
• climb up into a four-wheel drive vehicle
• decreased or halted fasciculations
• improved balance and less falls when walking
• put our arms over our heads and wash our bodies and hair unassisted
• use the bathroom or hold a urinal
• open water bottles, pill bottles and food jars
• hold a pen to write
• use a cell phone to text and type
• speak more clearly without needing a caregiver to translate
• pull the throttle on a lawnmower and push the lawnmower to mow the grass
• grip a glass and lift it to drink
• operate a wheelchair with one finger
• throw a ball to the dogs or throw rocks with the kids
• swallow dense foods like fried chicken, rice, sushi
• speak for longer periods of time between use of bipap
• breathe stronger as evidenced by improved FVC

Because of these improvements in function after receiving NurOwn, we were able to make memories with our families by going on camping trips, weeklong vacations to Disneyworld, attending our children's graduations, celebrating birthdays and anniversaries, and watching our children being born.

We further believe that the FDA cannot make any assessment of whether a therapy has a "clinically meaningful" impact without allowing scientific discourse and hearing opinions from the world's most esteemed ALS neurologists who were principal investigators in the trials and EAP. With decades of expertise with ALS, they are the only people in the world who have seen the clinical and biomarker data -- as well as observed our function in clinics. Many of our neurologists have publicly and privately expressed the belief that NurOwn works. Any scientific discourse about whether NurOwn works must include the scientists who know it best.

Moreover, several of us also would like to offer opinions from other health care professionals such as unaffiliated neurologists, pulmonologists, and physical therapists, who can attest to the changes they observed in clinic visits.

For example, Paula Smith is the mother of Josh Smith. She stated:

My son Josh is 33 years old. He was in the NurOwn trial and both EAPs. Josh was diagnosed in March of 2019, and he is still walking, talking, eating, and breathing. During the EAP, my son's pulmonologist documented a 41% improvement in his breathing function. Our outside doctors can't believe the changes in my son.

Combined with the many patient reported outcomes like this, the "totality of the evidence" in the trials and EAP proves NurOwn had a clinical and biological effect. We are asking the FDA to exercise its promised regulatory flexibility. We are asking for an opportunity to share our evidence at an Advisory Committee meeting. We are proof that NurOwn works. Please don't let us die waiting.

Collectively, we are the patients and family members of patients who participated in the NurOwn trials and Expanded Access. One of us participated in the NurOwn Phase II trial in 2015, which now has been unblinded. The balance of us participated in the Phase III trial from 2017-2019, which has not yet been unblinded; however, each of us received doses of NurOwn in the Expanded Access Program in 2021 and 2022.

• Eric Stevens (33). California. Expanded Access at UC Irvine. 
  Symptom onset in March 2019. Diagnosed with ALS in September 2019.
• Matt Klingenberg (37). South Dakota. Expanded Access at Mayo.
  Symptom onset in November 2017. Diagnosed with ALS in March 2018.
• Josh Smith (33). Pennsylvania. Expanded Access at UMass.
  Symptom onset in June 2018. Diagnosed with ALS in March of 2019.
• Phil Green (52). California. Expanded Access at UC Irvine.
  Symptom onset in June 2017. Diagnosed with ALS in August of 2018.
• Roberto Muggli (47). Costa Rica and Minnesota. Expanded Access at Mayo.
  Symptom onset in Spring of 2017. Diagnosed with ALS in December 2017.
• Kylan Morris for her mother, Sandy Morris. California. Expanded Access at CPMC.
  Symptom onset Aug 2017. Diagnosed with ALS in January 2018. 
  Died waiting at 56 years old in 2022.
• Nicole Cimbura for her husband, Mike Cimbura. Colorado. Phase II trial at Mayo.
  Symptom onset in May 2014. Diagnosed with ALS in January 2015.
  Died waiting at 53 years old in 2019.

On November 10, 2022, Brainstorm Cell Therapeutics announced that the U.S. Food and Drug Administration issued a Refusal to File ("RTF") letter for its investigational biologic treatment, a mesenchymal stem cell therapy called NurOwn. On November 14, 2022, in its quarterly call, Brainstorm provided more insight into the FDA's reasons for the RTF letter and its plan to request a Type A meeting with the FDA to discuss a path forward for its therapy.

Amyotrophic Lateral Sclerosis ("ALS") is a rare, progressive, fatal neurodegenerative disease that paralyzes you before it kills you. It results in the loss of motor neurons in the brain and the spinal cord. Those motor neurons are responsible for communicating with the voluntary muscles. As ALS progresses, people with ALS experience muscle weakness and atrophy, causing them to lose the ability to move, speak, eat, swallow, and eventually breathe. Average life expectancy for people with ALS is three to five years from the time of symptom onset, but life expectancy varies with 50% of the population dying within two years. According to the CDC's ALS Registry, approximately 6,000 people are diagnosed with ALS each year and 32,000 people are living with the disease. Sadly, 500,000 people living today will be afflicted with ALS in their lifetime.

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SOURCE Stevens Nation