√ Magenta Therapeutics Good News-Bad News Trial Data

Magenta Therapeutics is a biotech company with a portfolio including stem cell products. Their most well known investigational drug product is an expanded umbilical cord stem cell product called MGTA-456, an “ex-Novartis” product. Magenta just released new trial data on MGTA-456, which I see as a case of good news-bad news, and investors seem to have had a similar reaction.

Image from Magenta on MGTA-456.

The company describes MGTA-456 as, “a first-in-class allogeneic stem cell therapy consisting of a single umbilical cord blood unit expanded with an aryl hydrocarbon receptor (AHR) antagonist then administered to a patient through a bone marrow transplant.” A key feature of the product is its higher cell dose. You can see an image from the company explaining the idea behind the production and use of MGTA-456.

As FierceBiotech points out, the good news from data from abstracts for the upcoming ASH meeting is that there are some signs of strong efficacy:

“MGTA-456 is an ex-Novartis therapy, based on cord blood-derived stem cells, that aims to improve the dose that can be delivered in allogeneic hematopoietic stem cell transplants (HSCT)—an important therapy for patients with inherited metabolic disorders such as Hurler syndrome who don’t have a matched donor.

By allowing a larger cell dose, MGTA-456 is intended to reduce the time it takes for white blood cell populations to recover after HSCT, which involves destruction of the bone marrow as a first step. The new data shows that using MGTA-456 cut that to one day from a historical average of around eight days.

Moreover, all five patients treated—two with Hurler syndrome and three with adrenoleukodystrophy—met the main objective of successful stem cell engraftment 42 days after the transplant, which tops historical success rates of around 32% with regular, unexpanded cord blood transplants.”

This is encouraging, but one “asterisk” here is that this is such a small group of patients (N=5) that we should be cautionary at this point. Note that Hurler Syndrome is also known as mucopolysaccharidosis type IH.

Unfortunately, the bad news here is that the two pediatric patients with Hurler syndrome both had adverse events in the form of autoimmune cytopenia in each case. One died. Magenta suggests based on feedback from “scientific leaders in the field” that the death was not necessarily related to MGTA-456, but I don’t see how they can be sure at this point. It’s reasonably possible that the allogeneic product caused the autoimmune reaction, but admittedly I’m definitely not an expert in that specific area. Further study with more patients will help clarify the risks here.

What does the future hold? Magenta is continuing with the work, will limit participation in this area to those older than the pediatric patients who had the adverse events, and also plans soon to study MGTA-456 in sickle-cell disease and possibly blood cancers.

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√ Perspectives: Fda Warns Umbilical Firm Continues Stream Of “Mini-Warning” Letters

Cropped Flickr image labeled for reuse

Yesterday we learned that the FDA issued a warning letter to the cord stem cell firm, Cord for Life. In this warning, the FDA indicated that the firm’s product is actually a drug product and lacks necessary pre-market approvals. In addition, the agency highlighted apparent deviations from CGMP practices.

The most important part of the warning letter is the clarity it brings that, yes, allogeneic umbilical cord stem cell and other perinatal stem cell products generally are drugs requiring a cleared IND and a BLA. In other words, you can’t just market such perinatal stem cell products including amniotic and placental materials without working with the FDA.

A striking press release (PR) accompanied the warning to Cord for Life with broader implications. In it the agency reaffirmed its stepped-up actions against non-compliant stem cell clinic and supplier firms more generally. Under the leadership of Commissioner Dr. Scott Gottlieb and CBER Director Dr. Peter Marks, this co-released warning letter and PR continues a demam isu of much greater transparency and stronger language by the agency in regard to stem cell clinic-related firms.

The PR also indicates a continued demam isu of the agency issuing dozens of what I’m calling “mini-warning” letters to firms it sees as high-risk, non-compliant businesses marketing unapproved stem cell drug products. It seems these mini-warning letters are meant to indicate to these firms that their time is running out to become compliant. Note that the term “mini-warning letter” is not something the FDA uses or even necessarily approves of others using, but it seems apt to me.

The PR nicely sums up recent FDA actions including the mini-warning letters in this passage:

“Over the past year, we have sent 45 manufacturers and health care providers regulatory correspondence, including warning letters, and we have two court cases pending. We’re committed to taking appropriate steps to address those that jeopardize the health of the people we are sworn to protect.

“Today, we’re continuing these efforts. The agency issued a warning letter to Cord for Life, Inc., located in Altamonte Springs, Florida, for manufacturing unapproved umbilical cord blood products in violation of current good manufacturing practice (CGMP) requirements, including failing to validate processes to prevent bacterial contamination, raising potential significant safety concerns that put patients at risk. In addition, we issued 20 letters today to separate manufacturers and health care providers across the country who may be offering unapproved stem cell products, reiterating the FDA’s compliance and enforcement policy.”

Overall, I’d say Gottlieb and Marks are doing a great job addressing the unproven stem cell clinic problem. Although Dr. Gottlieb is moving on from the FDA very soon (tomorrow, I think), I expect the stepped up action on clinic-related firms to continue accelerating under the leadership of Acting Commissioner Dr. Norman E. (Ned) Sharpless working with Dr. Marks.

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√ Dissecting Liveyon Fda Inspection Report Troubled Perinatal Stem Cell Industry

The perinatal stem cell clinic supplier Liveyon has had many issues recently including an FDA inspection that  in my view didn’t go well and which I’ll return to in a minute. First, some background on the company and this troubled industry.

Liveyon website screenshot.

E. c0l1 and other pathogens ended up in some of the Liveyon product somehow prior to injections of it into patients at clinics. There was the recall.  A dozen or more patients ended up in the hospital. Patients lawsuits stemming from that are pending.

Then there was the recent scathing (appropriately so in my opinion) investigational report on the perinatal stem cell clinic industry co-published by The New Yorker and ProPublica by Caroline Chen in which Liveyon featured prominently.

More broadly, the unproven perinatal “stem cell” industry is a chaotic but growing sector that in my opinion has little benefit to offer patients in the way of proven safe and effective products. It does pose many risks.

I’ve regularly covered this subsector of the larger unproven stem cell clinic field within the even larger overall stem cell ecosystem for years. It’s been hard to watch and in my view, it is not only generally bad for patients, but also is harmful to legitimate research on perinatal stem cells.

Liveyon has tried to reboot itself more recently with a “new supplier” (basically itself?). From Chen’s report:

“Now Liveyon is making its own product, from umbilical cords that it buys from a public cord bank, Kosolcharoen said. The bank, which he declined to identify, sells donated cords that don’t meet FDA standards for treatment of blood disorders, he said. Liveyon, he noted, uses them for a different purpose — to create stem cell products. He called the new treatment “clinical trial grade” and said that Liveyon plans to start trials to prove its safety and benefits. But, even before conducting trials, Liveyon is already marketing the product, which it calls Pure, with the tagline “The Pure Feeling of Healing.”

So circling back, some months ago, Liveyon was also inspected by the FDA. I found the 483 inspection report, which you can see here.

In my view the report isn’t good, to put it mildly.

Eight observations (I would translate the FDA-speak “observations” here to “problematic issues”) were listed including in my view some very serious ones. There are also more than 8 issues here overall as some of the observations have many separate bullet points such as “Observation 1” listing a number of serious adverse events.

Utan Cord Bank products screenshot from website.

Other specific issues mentioned by the FDA include deviations from proper testing and handling of their umbilical product. It’s not exactly confidence building.

The broader perinatal stem cell industry is very concerning and was a major focus of Chen’s article. Liveyon has some competition in this sector from other suppliers including perhaps most prominently the firm called Utah Cord Bank. For instance, a stem cell clinic doc named David Greene reportedly gets a product from Utah Cord Bank. Others do too. Chen spent a good amount of time digging into what Greene does and the history of Utah Cord Bank, including this telling passage:

“Around 2016, the bank began making two amniotic stem cell products, called StemShot and StemVive. (StemShot was later renamed Stemii.) Although the bank continued to store birth tissue, amniotic stem cells soon became its biggest moneymaker.

The Utah Cord Bank was co-founded by a man named Eliott Spencer, who holds a doctorate in biochemistry from Brigham Young University. When the bank started producing StemShot and StemVive, Spencer was the only scientist on the company’s management team and the only person who knew the recipe for making the products, according to two former employees who spoke on condition of anonymity. Spencer said in an email that the bank now has “more than one scientist and many technicians, as well as multiple people who know how to safely procure, process and package our products.”

Read Chen’s whole article. I highly recommend it.

Overall, in my opinion, the more we learn about the perinatal stem cell industry the clearer it becomes that it is risky for consumers and has a slew of problems. I believe that more action by regulators is urgently needed including the FDA, the FTC, and state bodies.

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