One Nation Under a Groove

The OG of funk, George Clinton. There’s not much that hasn’t been said about him. He is a visionary, eccentric and willing to let his freak flag fly high. He has been a powerhouse of music for the past 50+ years. He was born in NC, the moved to New Jersey in the 50’s when he formed his first doo-wop group, Parliament. Over the years, he transitioned from doo-wop, to soul, and then to funk with his bands Parliament and Funkadelic. Along his ride, he cultivated numerous musicians in his groups, from Bootsy Collins to Maceo Parker to Eddie Hazel to Berne Worrell, and on and on. If I named everyone that’s been in his various bands over the years we could be here a while! In the 70’s these two bands toured together as a supergroup, a mad party on stage that came with over the top costumes, props, and even a full sized spaceship called the mothership. Mothership Connection was one of Parliaments best albums, and during the show the mothership would land from above the stage and George would walk off in character as Dr. Funkenstein, strutting off the mothership to the delight of the crowd. Throughout the show there would be numerous southern and theme changes. Their scene was one of decadence, sex, drugs, and funk. It was a party, and throughout the night the crowd felt like they were part of it.

I remember one of the Parliament Funkadelic shows I saw, obviously many years later, up in Milwaukee. They came on at about 9 o’clock, and didn’t stop funking until about 330 or 4am. No set breaks, no stopping the groove. Musicians would rotate on and off without missing a beat. Sometimes there would be as many as 20 or so people on stage. They continued to push the energy, further and further, until everyone on stage and in the audience was ready to collapse. When it was over I was so exhausted and exhilarated all at the same time, like I had been through a great musical journey. It was one of the best shows I had ever seen, and one I’ll never forget. I had a permanent-grin for the next week or so afterwards.

The reason why I bring up One Nation Under a Groove, one of Funkadelics best songs, is because of recent CF news (article is below from FDA). You may have read about Trifekta, a CFTR modulator that should help up to 90% of the CF population, that was quickly approved by the FDA. The reason they were able to fast track the approval was because of the great data in the clinical trials. I was one of the test subjects; most of you know that I’ve been involved in trials for years. This drug approval was the endpoint of the years of ups and downs, failed combinations and subsequent exacerbations, trying to get back to the magical 40% FEV to continue to qualify for the trial. In the past 6-7 months during my “open label,” I have been taking the drug that is now called Trifekta with great improvement of my symptoms. I have been able to avoid hospitalizations for almost 11 months now, which is fantastic. My day to day symptoms are a lot better, and I have been able to feel more like I had hoped for all those years. So why didn’t I tell everybody about this earlier?

There’s a couple reasons for that. I could not give too many specifics or name the drug or the company due to the ongoing trial; if I did that I could have been disqualified. There are some very strict rules that are set in place by the review board to ensure that the drug is beneficial on its own merits and without any bias. So, I was not going to mess that up! The other and more important reason, why it has taken me a few weeks to write about this, is guilt. Guilt about the part of the CF population that cannot take this drug for one reason or another. It’s difficult to talk about your success when plenty of others are struggling to stay healthy. I equate it to survivor’s guilt of a mass tragedy. On one hand, you are grateful and happy for your good fortune. However, you keep that happiness inside, as to not feel like boasting to those who are suffering. That’s how I feel about this drug; I am very happy with the benefit it has given me but I am also sad and feel slight embarrassment sharing that happiness as many other people are continuing to struggle.

My hope is that this great research and therapies that have improved so many lives will continue to gain momentum, until all CF patients can benefit from this cutting age medication. So, to the community out there: keep hope and faith alive, continue to look positively to the future, and don’t give up until a cure is found!!

Article from FDA:

The U.S. Food and Drug Administration today approved Trikafta (elexacaftor/ivacaftor/tezacaftor), the first triple combination therapy available to treat patients with the most common cystic fibrosis mutation. Trikafta is approved for patients 12 years and older with cystic fibrosis who have at least one F508del mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, which is estimated to represent 90% of the cystic fibrosis population.

“At the FDA, we’re consistently looking for ways to help speed the development of new therapies for complex diseases, while maintaining our high standards of review. Today’s landmark approval is a testament to these efforts, making a novel treatment available to most cystic fibrosis patients, including adolescents, who previously had no options and giving others in the cystic fibrosis community access to an additional effective therapy,” said acting FDA Commissioner Ned Sharpless, M.D. “In the past few years, we have seen remarkable breakthroughs in therapies to treat cystic fibrosis and improve patients’ quality of life, yet many subgroups of cystic fibrosis patients did not have approved treatment options. That’s why we used all available programs, including Priority Review, Fast Track, Breakthrough Therapy, and orphan drug designation, to help advance today’s approval in the most efficient manner possible, while also adhering to our high standards. The FDA remains committed to advancing novel treatment options for areas of unmet patient need, particularly for diseases affecting children.”

Cystic fibrosis, a rare, progressive, life-threatening disease, results in the formation of thick mucus that builds up in the lungs, digestive tract, and other parts of the body. It leads to severe respiratory and digestive problems as well as other complications such as infections and diabetes. Cystic fibrosis is caused by a defective protein that results from mutations in the CFTR gene. While there are approximately 2,000 known mutations of the CFTR gene, the most common mutation is the F508del mutation.

Trikafta is a combination of three drugs that target the defective CFTR protein. It helps the protein made by the CFTR gene mutation function more effectively. Currently available therapies that target the defective protein are treatment options for some patients with cystic fibrosis, but many patients have mutations that are ineligible for treatment. Trikafta is the first approved treatment that is effective for cystic fibrosis patients 12 years and older with at least one F508del mutation, which affects 90% of the population with cystic fibrosis or roughly 27,000 people in the United States.

The efficacy of Trikafta in patients with cystic fibrosis aged 12 years and older was demonstrated in two trials. The first trial was a 24-week, randomized, double-blind, placebo-controlled trial in 403 patients who had an F508del mutation and a mutation on the second allele that results in either no CFTR protein or a CFTR protein that is not responsive to ivacaftor or tezacaftor/ivacaftor alone. The second trial was a four-week, randomized, double-blind, active-controlled trial in 107 patients who had two identical F508del mutations.

In each trial, the primary analysis looked at increases in the percent predicted forced expiratory volume in one second, known as ppFEV1, which is an established marker of cystic fibrosis lung disease progression. Trikafta increased the ppFEV1 in both trials. In the first trial, it increased mean ppFEV1 13.8% from baseline compared to placebo. In the second trial, it increased mean ppFEV1 10% from baseline compared to tezacaftor/ivacaftor. In the first trial, treatment with Trikafta also resulted in improvements in sweat chloride, number of pulmonary exacerbations (worsening respiratory symptoms and lung function), and body mass index (weight-to-height ratio) compared to placebo.

The safety profile of Trikafta is based on data from the 510 cystic fibrosis patients in the two trials. The safety profile was generally similar across all subgroups of patients. Serious adverse drug reactions that occurred more frequently in patients receiving Trikafta compared to placebo were rash and influenza (flu) events. The most common adverse drug reactions included headaches, upper respiratory tract infections, abdominal pains, diarrhea, rashes, increased liver enzymes (alanine aminotransferase and aspartate aminotransferase), nasal congestion, increased blood creatine phosphokinase (an enzyme that can be associated with muscle damage), rhinorrhea (mucus in the nasal cavity), rhinitis (swelling of the mucous membrane of the nose), influenza, sinusitis and increased blood bilirubin (may be caused by problems involving the liver, gallbladder or red blood cells).

The prescribing information for Trikafta includes warnings related to elevated liver function tests (transaminases and bilirubin), use at the same time with other products that are inducers or inhibitors of another liver enzyme called Cytochrome P450 3A4 (CYP3A), and the risk of cataracts. Patients and their caregivers should speak with a health care professional about these risks and any medicines they take before starting treatment.

Patients with cystic fibrosis should speak with a health care professional and have tests performed to understand which gene mutations they have. The presence of at least one F508del mutation should be confirmed using an FDA-cleared genotyping assay prior to treatment. The safety and effectiveness of Trikafta in patients with cystic fibrosis younger than 12 years of age have not been established.

The FDA granted this application Priority Review, in addition to Fast Track and Breakthrough Therapy Designation. Trikafta also received orphan drugdesignation, which provides incentives to assist and encourage the development of drugs for rare diseases. Drugs approved under expedited programs are held to the same approval standards as other FDA approvals. Because of Trikafta’s benefit to the cystic fibrosis community, the FDA reviewed and approved Trikafta in approximately three months, ahead of the March 19, 2020 review goal date. The approval of Trikafta was granted to Vertex Pharmaceuticals Incorporated, which will receive a Rare Pediatric Disease Priority Review Voucher for developing this therapy.

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