Biosimilars And Complex Medicines For All With RNA Therapeutics' Sarfaraz Niazi, Ph.D.

On this week's episode of the Business of Biotech, we speak with Dr. Sarfaraz Niazi, Ph.D., about how biosimilar regulations have taken shape, from early FDA uncertainty to citizen petitions, lawsuits, and guideline changes. Dr. Niazi offers a behind the scene look at the way FDA policy gets made, and unmade, and his own role in key regulatory changes, and legislation such as the Biologics Price Competition and Innovations Act (BPCIA), and the Inflation Reduction Act (IRA). We also discuss Dr. Niazi's current company, RNA Therapeutics, and his quest to make new drug modalities accessible to patients around the world.     

This episode of the Business of Biotech is brought to you by Cytiva. 

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Transcript

Sponsor Message From Cytiva

Ben Comer 0:01

This week's episode is brought to you by Cytiva. Navigating the path to biosmilar approval can feel complex. Regulatory expectations are evolving, timelines are tight, and the cost of missteps is high. But you don't have to navigate it alone. As a trusted collaborator in biosimilars manufacturing, Cytiva brings deep regulatory insight and real-world experience to help you minimize risk, improve efficiency, and move forward with confidence. From understanding global regulatory expectations to aligning your process with approval requirements, Cytiva works alongside you, wherever you are on your journey. Visit Cytiva.link/regulatory and discover how Cytiva helps you stay in control from development to launch. Welcome back to the Business of Biotech. I'm your host, Ben Comer, Chief Editor at Life Science Leader, and today I'm speaking with Sarfaraz Niazi, Ph.D, CEO at RNA Therapeutics, a company developing biosimilar mRNA therapies, the CTO and co-founder at ABYOLO, a startup global biosimilars company, and the CEO at Dey Therapeutics, a company developing generic GLP-1 therapies. We'll talk with Dr. Niazi about his experiences as a researcher, company leader, and advocate for biosimilar policy change, his impact on key FDA regulatory actions, and what still needs to change to make novel and complex medicines affordable to patients all over the world. We'll also learn about Dr. Niazi's current work uh in the mRNA space at RNA therapeutics. Dr. Niazi, I'm pleased to have you on the show. Thanks so much for being here.

Sarfaraz Niazi, Ph.D. 1:51

Thank you so much.

Ben Comer 1:52

I'd like to start off uh with your background. Um, you got a uh Ph.D uh from the University of Illinois, Chicago, and uh and then subsequently moved to Abbott International. I'm curious about what interested you initially, Dr. Niazi, about pharmaceutical science and and why you decided to choose that field.

Sarfaraz Niazi, Ph.D. 2:15

Okay, so I'll I'll give you a very short history. Okay, so um uh I started on the um uh academic side as an uh assistant professor in 1974. And then I was promoted to a tenured professor in 77 at the age of 27.

Ben Comer 2:40

Impressive, impressive accomplishment.

Sarfaraz Niazi, Ph.D. 2:42

Now that has a negative impact. Let me tell you what it is. You you are so uh enthused about everything you wanted to do, and one of the projects I had uh a small project was from Abbott Company to make a shampoo for them, which they couldn't make it. It's called Selsun blue.

Ben Comer 3:03

Yeah, for dandruff, right?

Sarfaraz Niazi, Ph.D. 3:05

Yeah, so I made the shampoo, I reduced the contents, and you know, I met with uh uh so they used to have um every year a uh a dinner for what they call Volwiler fellows. So Volwiler was the person who started Abbott. So um what they do once they make you fellow, it's like a tenure ship. They cannot let you go. Okay.

Ben Comer 3:32

You have employment at Abbott for life after that.

Sarfaraz Niazi, Ph.D. 3:35

Yeah, no, no, yeah. So he asked me, you know, you want to come down and work for us? And I was so full of myself. I says, Me go down to work for a company? Hello. This guy was a younger guy, a very smart guy, and he says, Um, Dr. Niazi, I'm going to make you an offer you can't refuse. That was a dialogue uh from uh Godfather. Okay, he said, uh, your job will be to do what you like and like what you do. I said, Wow, not a bad job. You know, new products. So I said, Okay, so I got out of my tenure ship, which was very unusual for anyone to do that, and then I start going around finding out what are the needs of there were 47 Abbott affiliates around the world. So I traveled them, I got them new products, and after two years I was made a fellow myself. Okay, and um then after about three more years, okay, I resigned. And uh again, this was the second time I let my tenureship go. When I saw that the future is not going to be chemical drugs, you know. Um, I used the pun, okay. I used to call uh there's a pharmacy inside our body, which is open 24-7. Okay, and that's a fact, okay. Um how we survived for millions of years, okay, it's not because of uh any drug or any process. These are all very recent things, okay.

Ben Comer 5:18

And you made this decision because you saw what was happening with monoclonal antibodies, yeah, and on the biological drugs.

Sarfaraz Niazi, Ph.D. 5:25

So moving from academia to industry was um uh uh challenging, but I think it was very uh significant because I could see where the needs are. Okay, you know, even today uh when uh um a good part of the world cannot even afford insulin, okay. Right, there's a lot of diversity and um misbalance. Okay, so then I got into um making biologicals. Okay, and uh I was very fortunate to have a friend uh in ICGEB, which is in Italy, it's an institution sponsored by UN, and their goal is to give biotechnology to developing countries. So we sat there in um um and several times and we made many products, and I just gave it away to many uh other um companies in in developing countries.

Ben Comer 6:30

And this was your first uh this was your first time as a company leader, is that right? The the company you established uh through that partnership?

Sarfaraz Niazi, Ph.D. 6:39

Well, at that time I didn't have my company, I was acting as an advisor to or consultant to many companies. Okay. Um it was only in the early 2000, okay, I think uh one or two uh that I established my own company in the US.

Ben Comer 6:57

And what company was that?

Sarfaraz Niazi, Ph.D. 6:59

Oh, that is called Therapeutic Proteins, TPI. Very uh, it was a good name then. Um it was then bought out, it became changed the name two, three times, okay. And that's where when I started okay at that point when there was no biosimilar name. Okay, there were no biosimilars.

Ben Comer 7:22

Yeah, what year what year was that?

Sarfaraz Niazi, Ph.D. 7:24

Uh, it was year 1999.

Ben Comer 7:27

Okay.

Sarfaraz Niazi, Ph.D. 7:28

Okay, so I wrote my first book, uh, and I called it biogeneric therapeutic proteins. You know, that's what the whole point was. So MG said, no, no, no, no, you cannot do this, okay? There's a legality involved in the term generic.

Ben Comer 7:47

Okay, it's very specifically prescribed what that term generic means.

Sarfaraz Niazi, Ph.D. 7:52

Yeah, the rules that apply.

Ben Comer 7:54

Yeah.

Sarfaraz Niazi, Ph.D. 7:55

So I said, how about if you call it biosimilar? Not similar biologics, a big difference. So they are biological products that happens to be similar, not similar products that are biologics. I mean that sounds like a good idea, anyways. The same book, you know, was then my second or third edition. Now we're calling it biosimilar, it's not biogenetic. But the point was that FDA had no guideline.

Ben Comer 8:26

Okay, they had no framework for developing biosimilars, right?

Sarfaraz Niazi, Ph.D. 8:30

Because these were biological drugs, okay. So they had plenty of things for genetic drugs. Okay. Now, generic drugs come under uh CDER, not C BER, and all the biologics were in CBER. So I had I was very lucky. Um, I met several folks and FDA, and uh they were and I uh understood how is they operate. That was the most important thing, okay. Um, they're not here to take the risk for you, they don't care about the cost. Okay, they're not going to let you do something that you don't ask for. Those three things, if anybody knows, okay, they know how to handle FDA. Okay. So that was the story, okay. But my story is a long, okay. How we got into FDA and then uh got the products approved and so on. Okay, so that's how I changed from academia to industry and then back to on my own.

Voice Of America And Big Ideas

Ben Comer 9:37

Yeah, and I I want to get back to uh by the biosimilar policy development over these years. Uh, a lot has happened, and I want to ask you about some of those policies and and your role in them. But before I do that, I have to ask about Voice of America. I saw on your LinkedIn profile, Dr. Nyazi, that you had a radio show for eight years, over eight years at Voice of America. And I have to ask what that experience was like, and what what was your show?

Sarfaraz Niazi, Ph.D. 10:06

Okay, I'm I'm so happy you're asking about things that makes all of us uh human beings, okay? So the Voice of America, as you know, they are mainly international, okay. So they asked me if I want to talk about some poetry and some literature, okay, and they wanted to start something. And it was every Sunday, okay, that I have to record my program. So the first few programs, I was very nervous, I didn't know what to say and whatnot. Then my audience grew into millions. Wow, millions, and then I became very comfortable with the starting without any topic in mind. It was a very common conversation. So today we are talking about why should you not lie? And I will have a 20-minute talk. We talked about science, we talked about Darwin, we talked about um genetic engineering, we talked about religion, which was the most difficult topic, okay. And for eight years, okay, uh, it grew into more than 100 million people.

Ben Comer 11:35

Wow. Well, and this was uh the format you were you talking to other people, were you having guests on, or was it just the soliloquies from Dr. Niazi?

Sarfaraz Niazi, Ph.D. 11:44

Just my speech.

Ben Comer 11:45

Oh, wow, okay.

Sarfaraz Niazi, Ph.D. 11:46

It's like a teacher, okay? I don't know teacher all my life.

Ben Comer 11:50

You're a professor, yeah, of course.

Sarfaraz Niazi, Ph.D. 11:52

And today I walk in there, okay, and uh, we're gonna have a Voice of America program, okay? Ben, what do you think is the most significant issue with biosimilars? So I'm not talking to my cell phone. You know what? Biosimilars are biological drugs, okay. All right, and when a new drug is approved, it is what it is, okay? There are no rules as to which drug will be used. Okay. So I told FDA, by the way, Ben, that a biosimilar should be just as bad as the reference product. Okay.

Ben Comer 12:29

Right, yeah.

Sarfaraz Niazi, Ph.D. 12:29

But if you don't want to, if you want to make it better, then you have to go through all the trials, you know. So let me then talk about. So that's how the topic starts, okay, and then I go into, but I really enjoyed uh the uh topics in philosophy. Okay. Um, one of my most uh favorite, well not not favorite, but was I said, Do you know Socrates? Do you know he was totally wrong?

Ben Comer 12:59

That'll attract some listeners, yeah.

Sarfaraz Niazi, Ph.D. 13:01

You know, Socrates, when he was told that we have invented the fountain pill, he said this is the demise of mankind. And do you know? I'm talking to my audience, he never wrote a single word on paper?

Ben Comer 13:20

Right - nothing extant at least.

Sarfaraz Niazi, Ph.D. 13:20

What we know about him is what others wrote, right? But that was not bad enough, okay? Uh there was a fellow who created printing press.

Ben Comer 13:34

Gutenberg.

Sarfaraz Niazi, Ph.D. 13:35

Yeah, and you know who got very upset, Catholic Church.

Ben Comer 13:39

Yes.

Sarfaraz Niazi, Ph.D. 13:40

What do you mean? You're gonna have a copy of the Bible which is not handwritten. So my dear, and I'm talking to my audience, okay. You know, human history is so full with surprises. By the way, there was a fellow who said that earth goes around sun. You know what they did to him? They killed him.

Ben Comer 14:03

Yeah, okay.

Sarfaraz Niazi, Ph.D. 14:04

So be ready for big surprises, okay. What you know today may change entirely tomorrow and keep your mind open. So these are the kinds of topics I had, okay. And uh God, I I talked about uh everything, what the birds think. Um why do uh birds have a different quality than human beings have? I mean, all these things were all philosophic, and that's why it was popular because they didn't know, I didn't know what is coming up next, okay.

Ben Comer 14:38

Yeah, I that sounds like a really interesting show and something something I would have tuned into. Yeah.

Sarfaraz Niazi, Ph.D. 14:44

I'm the same token, okay. I have also written books and topics which like um I I did the translation of Persian poetry, Arabic poetry in English. And these are very large books. And I had to go back to school to learn the language again. And uh so I uh I get involved in a lot of things other than uh my professional work, okay, which is to bring make drugs accessible and affordable to all living beings.

Naming Biosimilars And Early FDA Gaps

Ben Comer 15:18

Yes. Well, there are some, I think, solid philosophical principles uh beyond that, um, beyond that objective or underscoring that objective. I want to ask you so you you were around for the very earliest development of biosimilar drugs. Can you give me a sense maybe of what it was like to take a biosimilar drug through regulatory approval in those early days? Was there the expectation that you had to follow the same you know um requirements uh as you know a brand new innovative new drug? I mean, was that was that the requirement uh at first?

Sarfaraz Niazi, Ph.D. 15:58

You know, uh, first of all, let me uh uh this is the question which I love to give you a very structured answer because it's important.

Ben Comer 16:07

Okay.

Sarfaraz Niazi, Ph.D. 16:08

Um when Barack Obama was elected president, um, you know, he's from Chicago.

Ben Comer 16:15

Yep.

Sarfaraz Niazi, Ph.D. 16:16

So I wrote to him that we have it issue. So he said, Come on down. So I went to see him in his office in Chicago downtown. Well, before he took the oath.

Ben Comer 16:25

This was when he was a senator.

Sarfaraz Niazi, Ph.D. 16:27

There's a picture here in my office, he and I, you cannot see it. And I explained to him what the issue is at that time. There were four or five bills in the Congress, but they were going nowhere. So he told me, he says, It will be done. So I said, How will it be done? He said, Leave it to me. I said, 'Okay.' See, what it did was he buried the BPCIA in the ACA, Affordable Care Act, which was 2,800 pages long, and those who voted didn't even know what they're voting for.

Ben Comer 17:08

And you're talking about the uh the Biologics Price, Competition, and Innovation Act. Exactly.

Sarfaraz Niazi, Ph.D. 17:15

That's where the biosimilar was established. At that time, he the act had an eight-year exclusivity, and then there were a lot of uh opposition, so it was moved to 12 years, he wasn't very happy with that. But the way the uh law was approved, uh, there were a lot of uh mistakes in there. Mistake means they just wanted to do it quickly, okay. So I said, let's do it, we'll talk about it later. Okay. So after the law was approved, FDA treated these almost like new biological drugs.

Ben Comer 17:59

Right. And you mentioned, I just want to clarify something really quickly. You mentioned uh the 12-year provision or the eight and originally eight-year provision um in that law. Now it then it was kind of moved uh to 12 years through some congressional bills, but that was that was saying that after 12 years a biologic drug would lose its patent expert, and thus biosimilars would be allowed to come into the market. I just wanted to mention that to the other.

Sarfaraz Niazi, Ph.D. 18:30

A new biologic drug gets 12 years of exclusivity. Okay. Uh, he wanted to make it eight years.

Ben Comer 18:38

So the first um I think it was Sen. Ted Kennedy who really came out strongly for the 12 years there, or was one of the major players in there.

Sarfaraz Niazi, Ph.D. 18:45

Yeah, I don't want to go into the names because I've been in so much trouble, okay, Ben.

Ben Comer 18:50

Okay, yeah, fair right.

The Biosimilar Guideline Fight That Changed Analytics

Sarfaraz Niazi, Ph.D. 18:53

So so he said, okay, what the heck, you know. Uh, was it good or bad? Uh, I don't know. But now I'm looking back, you know, it was okay, you know. I don't think it made a big difference. Okay. So, but what happened was the guidelines that FDA issued. Okay. By the way, when FDA issued the first guideline, they had a big meeting in Miami. Okay. And uh I was there, and so were all the big pharma. I can tell you one thing, and I hope you'll remember that. One of the big pharma kids, I call her a kid, okay. She got up and said, biosimilars will kill everybody. You know what? It is exactly the same statement repeated in 1982 when generics came in. Then the big pharma joined the generic field, then the bottom fell, and they walked out. So my representation was that this is exactly what will happen, but the role FDA has to play is very critical. That is not how it worked out, okay. That's how it worked out. Um, FDA hired folks from academia here and there, they wrote some guidelines, and that's where my I call it ambition began with FDA. Okay. Let me give you the first hurdle I had, okay, and then we'll go stepwise. Okay. Um they had a uh guideline which they call a tier-based analytics. Look at tier one, tier two, tier three, okay. Tier one was based on the standard deviation of the reference product. So my product, which I made in Chicago, met every requirement they call release spec. Okay, but it failed analytics. Why? Because analytics requires the content in the dose to be tier one, which means 1.5 times the standard deviation of a reference product, but the release specification allows me plus minus three percent. All right, so I got eight batches of my reference product, and I don't know how they do it. It was all 100%.

Ben Comer 21:28

Wow, okay.

Sarfaraz Niazi, Ph.D. 21:30

You know what that meant? The standard deviation is zero, and anything multiplied by zero, at least in my lifetime, is zero.

Ben Comer 21:38

Yes.

Sarfaraz Niazi, Ph.D. 21:40

So my products were 99, 98, uh 100%, but they all failed. So I filed a citizen petition FDA, and I said, Does that make sense? Uh protein content should not be tier one. Anyway, FDA is supposed to respond in 30 days, and they did not. But at that time, I had a good connection with the commissioner. Then I asked him, you know, what to do. And he said to me, and we had we met personally in, I think it was in Florida somewhere. He said, Dr. Niazi, I cannot tell them what to do. It's a technical issues, okay. All right. I can ask them, you know. But so it took another three months, no response. Then he told me, he says, you know what? Sue me. And I did.

Ben Comer 22:36

Wow, okay.

Sarfaraz Niazi, Ph.D. 22:37

You know what happened? What? After three days, they for the first time in the history, they withdrew the guideline. They didn't correct it, withdrew it, totally cancelled it. And after eight years, they issued a new guideline. 100% of what I had asked them to do.

Ben Comer 22:58

And this was on the statistical analysis between batches and between reference products and part of it, okay? Yeah.

Sarfaraz Niazi, Ph.D. 23:06

The protein content is allowed to be plus minus two, three percent. Okay. I mean, that's just fine.

Ben Comer 23:12

And that that variation happens because we're talking about living organisms, right?

Sarfaraz Niazi, Ph.D. 23:16

Yeah, that's okay. I mean, no, that was acceptable. So my argument was that my product is good enough for patients, but not good enough for FDA. Right. Now they remove entirely the tiered testing. But you know what the negative effect was that all through these years, okay, all the companies who were developing, they still wanted to follow the guideline which had been removed, but they thought this is what the FDA wants you to do. So they brought a new guideline. That was my first attempt, okay, to change it. By the way, they also removed the whole team they had hired to write their guideline. Um, they just fired them okay. They were so ticked off with them, okay. And then uh came the issue of uh demonstrating immunogenicity, okay. And I said every protein is supposed to be immunogenic. Okay, one of the protein which is the most immunogenic is insulin. So why should I measure immunogenicity? They issued a guideline removing the testing of immunogenicity.

Ben Comer 24:35

And what year was that?

Sarfaraz Niazi, Ph.D. 24:37

This was done in I would say about uh 20 14.

Ben Comer 24:41

Okay. All right.

Rethinking Immunogenicity And Animal Studies

Sarfaraz Niazi, Ph.D. 24:43

Done. All right, so far, so good, okay. Uh then I had a big issue uh and I published in Science Magazine that for biological drugs, animal testing means nothing. You know why? If you give to a rat uh some adalimumab, you know what the rat will tell you? Hey, that was a good food, okay. Give me I'm hungry, okay? They do not, they may not have the same receptor binding.

Ben Comer 25:13

Right. I was told recently uh by someone else on the Business of Biotech, uh, a gentleman named Thijs Spoor, who's the CEO of Perspective Therapeutics, and he said, Imagine if chocolate is the greatest drug to ever be invented, it wouldn't get past the animal studies and dogs.

Sarfaraz Niazi, Ph.D. 25:32

Well, that's a fact, okay. That's the wrong thing to do. Uh and at that time, a big form, and I will not give the name because I've been in trouble, okay? But one of the biggest ones, they got bevacizumab approved as a biosimilar. Uh and they submitted 18 animal toxicology studies in there, which FDA did not review, most of them. So I was giving a seminar in Basel, Switzerland, and that company was sitting there, okay, and my talk, and I took the liberty of asking them, I said, So you got bevacizumab approved. But I have one question for you. What do you have against animals?

Ben Comer 26:17

Okay, yeah. Yeah, well, you know, the other thing that uh that Thijs said is that do you want to be the first human being to receive a medicine that has not been tested in animals? Now you're talking about animal toxicology, or you're talking about, you know, which is not efficacy. That's there's some difference uh and some nuance there.

Sarfaraz Niazi, Ph.D. 26:38

toxicity, which is uh ridiculous, okay. So I publish a paper, and then I'm very lucky I found two senators, okay, who were willing to uh put this as a bill. The bill went to Congress. Sorry, first it went to Senate. I was invited to talk to them. So the lawyers they um coached me before I went to the floor and said, do not talk about kindness to animals, they don't give a damn about it. Say just talk about why you're here. And I told them, I said, if you are basing comparative toxicology as a basis of approval, you may end up approving a toxic product. You know what, Ben? That bill got 100% approval. And when uh Joe Biden signed it into law, he said, and I'm I'm going to quote you because it's in the press, okay? He said, I don't know about animals, okay. But I think Professor Niazi will be happy to see here this, okay. You know what? No, then FDA took it to second, third steps. Okay. Now they're talking about removing all animal testing. They just got a new guideline issued about three weeks ago.

Ben Comer 28:05

Yeah, right.

Sarfaraz Niazi, Ph.D. 28:06

Yeah. But the point is not that I'm trying to save money or trying to save something, but the point that I've been successful in telling is that if you're using a tech uh a process which is not sensitive enough, okay, then you may end up approving a drug which should not have been approved in the first place.

Ben Comer 28:27

Yeah.

Why Clinical Efficacy Tests Mislead

Sarfaraz Niazi, Ph.D. 28:27

So no more animals. Animals are gone. And then the biggest issue I had was doing what FDA calls clinical efficacy study. They use the word very carefully, CES, they call.

Ben Comer 28:43

Is it comparative efficacy studies or clinical efficacy studies?

Sarfaraz Niazi, Ph.D. 28:47

Yeah, it's a clinical efficacy study. Okay, but it is a comparative study.

Ben Comer 28:53

Okay.

Sarfaraz Niazi, Ph.D. 28:54

Now, let me uh uh so let me go up front and come back, okay? So uh I had a meeting with the FDA commissioner. Okay, he asked me so

Ben Comer 29:06

Which commissioner was this?

Sarfaraz Niazi, Ph.D. 29:08

The current one.

Ben Comer 29:10

Okay.

Sarfaraz Niazi, Ph.D. 29:11

Okay. So I sent it out. Let me give you a.

Ben Comer 29:13

Martin Makary, yeah.

Sarfaraz Niazi, Ph.D. 29:14

Let me give you an example what I'm talking about. I said, let's say you bought a two-carat diamond and a jewelry shop and they weighed it for you. Everything is nice. You go on, I said, Oh, maybe I got cheated. Okay, let me wait again on my bathroom scale. What's gonna happen? I said, to do clinical efficacy testing, you need two things. And I explained to him, and I'm telling you now because many people would like to hear it, okay. Why? First of all, you have to put in the paper writing how much difference is acceptable. Okay, nobody knows it. Is it 10%, 20%, 30%, 50%? Okay, let's take 30%. If the real if you are taking the same batch tablet one, tablet two, and testing it, they are less than one percent difference in a chemical drug. They will never fail. They cannot fail theoretically, and I based it on three papers I published on a uh uh very interesting hypothesis called Bayesian hypothesis. Okay, and I'll uh I want to tell you why because FDA got so excited about it that they issued a new guideline on Bayesian hypothesis. It's also an FDA about a month ago.

Ben Comer 30:46

Yeah, I saw that.

Sarfaraz Niazi, Ph.D. 30:47

Yeah, they reduced the testing of new drugs from two studies to one only, right?

Ben Comer 30:54

Yeah, it was all based on Bayesian statistical analysis, yeah.

Sarfaraz Niazi, Ph.D. 31:01

You know, is that let's say uh a subject gets tested and it comes out cancer positive. Okay, does this person have cancer or not? It depends on two things. Number one, what is the probability of him 20-year-old, 30-year-old, having this cancer, the p-value? That's one thing which you know. And then what is the p-value of the test being accurate? You multiply the two and you have the answer. So, what I'm saying is that if there is a uh no possibility of this failing, so every study that was conducted for biosimilarity had never failed. One study failed in Japan, and they said no, it shouldn't have failed. Okay, they pass it anyway. Okay, that was wrong. So I said, what you're doing now is uh abusing humans, but I faced a significant uh backlash. Clinicians said, and I gave many talks, okay. Said, I want to see data in patients because they're used to it. I said, you know, so do I. But what if I tell you that these data don't mean anything? No, I think it's still good to have it. That was the teaching inculcated into uh the clinicians by you know who. So I I had a a lot of uh I I published about 10 papers, uh six um um petitions. So FDA invited me. Say you come down here. Okay. So I went to a meeting, and at that time they've invited everybody, all the top guns and everybody, and they called it uh a listening meeting. And the minutes of the meeting they posted on regulations.gov, it's all there. Okay. So what I learned from the meeting is that FDA is not in the business of risk taking. Okay, but FDA is obliged to understand an intellectual argument.

Ben Comer 33:16

Right. Right.

Sarfaraz Niazi, Ph.D. 33:17

And they uh so they published a paper, I was the reviewer. Finally, uh after I met with FDA, I got the approval for one of my drugs, and I wanted that letter to be without any if and but. Don't tell me you cannot, you don't need to do study if. Period. I shared that letter with my friends and on LinkedIn, nobody believed me. They thought I made it up, okay. So I went back to my very, very dear friend Sarah Yim. She's the head of Biosimilars. Um, I'm really thankful to her, okay, for putting up with me. Uh they should have guidelines.

Ben Comer 34:02

Okay.

Sarfaraz Niazi, Ph.D. 34:03

But you know what, Ben? Still today, I get emails. Uh, how do we really not have to do anything, or do we do a little bit of it earlier and there? They're not believing it that you do not require clinical efficacy, not to save money. But if your product has already gone through analytical similarity, okay, so what you do, you go to the testing tier basis from less to more sensitive tests. Here you're going from more to less sensitive. That's why the FDA approved it.

The Real Cost To Build Biosimilars

Ben Comer 34:39

Yeah, and so um, Dr. Niazi, you're talking about you're you said, you know, this is it's not about saving money. You're you're you're presenting very scientific reasons for why these changes to the biosimilar regulatory pathway had to take place. However, for biosimilars to become accessed or accessible and affordable to people everywhere in the world, they will need to be made. So they will be need to make uh able to be produced at a lower cost. And so I guess what I'm what I'm saying is while maybe that wasn't your objective, that is a necessary piece to making these drugs more affordable and accessible worldwide by bringing down some of the costs associated with things like animal studies or comparative effectiveness studies or clinical uh effectiveness studies. Um, are there and and I I wanted to uh bring this up too because I I thought it was really interesting. We haven't talked about the Inflation Reduction Act, uh, the IRA, but I thought uh, and I don't know if you're familiar with this group, um I-MAK, the Institute for Medicines, Access, and Knowledge. There's a gentleman um Tahir Amin that's now running that group. Uh, but I remember him uh telling me that essentially it what was interesting about the IRA is that you know it it put these nine and 13-year periods for drug negotiation on small molecule and biologics almost as if it was attempting to codify the uh Biologics Price Competition and Innovations Act uh provisions on the pricing side instead of on the patenting side because companies had been really successful at extending the patent life uh of their biologics and thus preventing biosimilars from entering the market through various activities at the uh at the trade office at the US PTO. But what they but what the IRA was uh essentially trying to do is saying we're we're not concerned about the patent at this point. We're saying that if you've been on the market for 13 years as a biologic, uh the the price, you know, we we can now negotiate down on on the price. Is that is that your reading of the IRA as well?

Sarfaraz Niazi, Ph.D. 36:59

I'm so happy you brought the topic okay, and I'm so happy that you and I have a chance now to clear the clouds. Okay, good. Before you go there, I never I was told by some of the close friends at FDA never talk about cost.

Ben Comer 37:18

Don't well yes, uh the the FDA is cost agnostic, it doesn't matter to them in their impact.

Sarfaraz Niazi, Ph.D. 37:24

Okay, yeah. My only goal was to reduce the cost. But okay only, because otherwise, hey listen, why should I be worried about okay? Because but only way was to remove what is unnecessary. I would not go and tell them to remove something, knowing it's gonna reduce the cost, but it could add to the risk to patients. Never, okay. I think they understood my sincerity very well. Very well, okay. And um luckily uh for my claims uh on regulations.gov, okay, all of my communications are FDA posts. Every time I say I look to them, they post it.

Ben Comer 38:12

Okay.

Sarfaraz Niazi, Ph.D. 38:13

So all of my communication with them are there. So going back to the thing, that was the endpoint. And today, as you and I are speaking, I'm glad to tell you that the cost of a biosimilar, and this is not from somebody's calculation, but from my own uh work that I just finished, okay, is less than 10 million dollars for each biosimilar to develop a biosimilar, less than 10 million. And that will also go further down from 100 million.

Ben Comer 38:47

Yeah.

Inflation Reduction Act Myths Debunked

Sarfaraz Niazi, Ph.D. 38:48

Okay, so anybody who's listening, okay, don't pay attention to anybody giving you any cost other than that. Okay, and I'll tell you also today how we can keep the cost low. Let me go back to IRA. I was involved in the drafting of IRA. First draft. Okay. I met with um all the agencies, we talked about it. First of all, so let me give you a little bit of history, okay? After it was approved by the House uh, sorry, uh Senate, there was a big uproar to block it.

Ben Comer 39:33

Yeah.

Sarfaraz Niazi, Ph.D. 39:35

So I went ahead and published an emergency paper which talked about what is IRA and why people, even the biosimilar associations, are so lost at it. So, first of all, it has it only applies after exclusivity expires, not before. It is optional. You don't have to take it. It only applies to the top ten drugs, by the way, which today is not all biological.

Ben Comer 40:16

Yes, that's a good point. Yeah, that's that's correct.

Sarfaraz Niazi, Ph.D. 40:19

Whatever, it is optional. You don't have to take it. Okay, it only applies to 30% of the population who's getting Medicare.

Ben Comer 40:31

Yes.

Sarfaraz Niazi, Ph.D. 40:32

The issue that was raised by Biosimilar Association was as follows. And I wrote about it in my paper in the most critical terms, so literally telling them they don't know what they're talking about. They said that if the price of reference product is reduced, it will be less incentive for biosimilars to come in the market. Okay, now let me tell you what happened afterwards. Pfizer decided to cut his price down on his own. Okay. All right. So I asked him, okay. We were having some very tough conversations. I said, are you going to tell Pfizer not to do it? I said, again, let me tell you this again. I told him it is only applied after exclusivity. It is completely optional. You can say no, and that's fine, okay. You don't have to take it over. And the third point is that it is only when you are in the top ten drugs applying to Medicare only. Right. Okay, not to the 70% rest of it all. There was a big uproar. And what made me truly upset because I also went to uh Senate to talk to them about what what IRA means. Okay, so my paper explains everything. For the first time, I quoted what others have said about IRA in my paper.

Ben Comer 42:09

Okay. And where can we where can we find this paper?

Sarfaraz Niazi, Ph.D. 42:12

I'll send it to you, okay? You if you you know here's the thing uh there's a website called google.com.

Ben Comer 42:18

Yes.

Sarfaraz Niazi, Ph.D. 42:21

That's it.

Ben Comer 42:21

Okay, okay. All right.

Sarfaraz Niazi, Ph.D. 42:23

A very big journal, okay? And I told them this is an emergency, okay. So they published very quickly, okay. It still went through five uh reviewers, okay. Whatever happens.

Ben Comer 42:32

Okay.

Sarfaraz Niazi, Ph.D. 42:33

So the point is that everyone who has been um going against IRA, they have not read it carefully. Okay. All right. Now, my point is this, okay. Let's take the the drug called Eliquis, okay? That's the number one drug now, uh, chemical drug for anticoagulant. Okay.

Ben Comer 42:55

Blood thinner.

Sarfaraz Niazi, Ph.D. 42:56

After 12 years of exclusivity, what the US government is asking, would you reduce the price by 20%? You said, no, I don't want to do it. It's fine. You don't have to. This part is not understood, okay. And they have taken this uh as my personal goal or whatever it is, okay. My personal goal was and remains to bring the price down for products for which a biosimilar or generic cannot be made for some reason.

Ben Comer 43:29

Is that the case with Eliquis?

Sarfaraz Niazi, Ph.D. 43:31

Yes.

Ben Comer 43:32

Why is there no generic generic available?

Sarfaraz Niazi, Ph.D. 43:35

There is a patent involved in the process of manufacturing.

Ben Comer 43:38

Okay, it's a patent issue. Okay, got it.

Sarfaraz Niazi, Ph.D. 43:41

So, but uh, if you read my paper, okay, I would really very much like you to uh get back to me and see whether I made sense or not, okay. But it it it ended up with a lot of um issues with many, many some of the big companies. Okay, the association, medical association, pharma association, big pharma, they all opposed it. They're still opposing it all. I only tell them one thing. Just read it.

Ben Comer 44:11

Okay.

Sarfaraz Niazi, Ph.D. 44:12

Just read it. Okay. And it had nothing to do with 70% of your market. It had nothing to do with the force price reduction. They are calling it price control. It's not a price control, it's a price suggestion. If you are willing to take it, you can take it. Okay. And every company who was asked to do it, they did it. Nobody refused it. Because listen, if you reduce 30% price with 99.9% margin, you're still making money on.

Ben Comer 44:46

Yeah.

Sarfaraz Niazi, Ph.D. 44:47

So that part, I'm glad that we had this discussion today. Okay.

Ben Comer 44:53

Well, I want to I want to ask you before we run out of time about mRNA, what you're doing at RNA therapeutics. But but the last question I want to ask about biosimilars before that, uh, Dr. Niazi, is what else still needs to happen to make biosimilars affordable and available to anyone in the world who may need them?

Patents USP Standards And Manufacturing Reform

Sarfaraz Niazi, Ph.D. 45:16

Okay. So I'll make it very fast, okay, because I have already uh filed this request to FDA. Number one is that the only U.S. patent laws allows you to do re-patenting. Okay. And no no one else allows it. I'm also a patent attorney. Okay. Uh not by choice, but by need, okay. I I have 250 U.S. patents. Okay. If I had hired somebody to do it, okay, I'll go bankrupt. Okay. So it's a bar exam and I am qualified. That's the reason, okay. So USPTO had a bill uh to change that. Then in the last 24 hours of the voting, they pulled it out.

Ben Comer 46:06

Really?

Sarfaraz Niazi, Ph.D. 46:06

They pulled it out. So again, I want you to go to google.com and write Niazi USPTO. I published a very nasty paper against USPTO. I mean, it was as nasty a language that uh a general will allow, okay? They must be second thing is which is must much more sensitive and important. I was I'm also a consultant to US Pharmacopoeia. Okay. Very nice people and we agreed FDA had barred USP to create monographs. Don't do it. It was a published letter. I also published a paper. So write down Niazi USPTO, you will find that paper also.

Ben Comer 46:54

Okay.

Sarfaraz Niazi, Ph.D. 46:55

They barred it. So I said, let's let's play some tricks on it, okay? Let's call it release a specification. So what USP will do, they will get the reference product, they will create their specification, they will have the methods which are um a validated method. So you don't have to buy the reference product. All right, everything was fine until the paper got published. Okay. Then I think USP decided to pull back, most likely due to pressure from big pharma and USP. If that ever happens, okay, that will bring a significant cost reduction, significant and time. It will be no more than a common generic drug. Okay. So that is one thing, okay. And then let me see if I have another thing, okay, here, okay. Yeah. FDA also then has issued guidelines on continuous manufacturing, also on a self-uh-free synthesis. And my book, um, it was sponsored by Nature Magazine, is coming out on that topic. Okay. Also, FDA now allows for asking data from a smaller scale batches, which will save you millions of dollars. Okay, yeah. So there's a lot of things are coming up, okay, in the future, but the way it is today, I think we you and I are sitting in a dramatic time in the moment. I think uh this is the time for medium-sized and smaller companies to jump in now. I gave an interview in in Europe and uh I said uh the big pharma will soon get out of biosimilars. The big pharma issued a statement. No, two of them pulled out in two weeks. So I'm telling Ben today that um give yourself three to four years, all biosimilars will be made by no big company.

Ben Comer 49:00

Okay, so now is the time for small and medium-sized companies to get into biosimilars. All right, you heard it here first.

Sarfaraz Niazi, Ph.D. 49:07

No better time, okay. And right now there are 100 molecules available, only 14 are available in the U.S. People ask me why. These are the molecules which have a large sale. So if a big pharma announces that I'm making a biosimilar to molecule X with $10 billion sale, you know what happens?

Ben Comer 49:29

Pay to delay?

Sarfaraz Niazi, Ph.D. 49:30

It goes up, their stock price goes up. Oh, that's it.

Ben Comer 49:34

Yeah, yeah.

Sarfaraz Niazi, Ph.D. 49:34

I'm gonna make something so that I can score the $10,000. Okay, no way. So I think the the big change is coming. And one of the purposes of this talk with you is to encourage all the small at the medium pharma to become serious, okay? Don't get swayed by the what is being put in your mind through anyone. Okay, just get to FDA and ask them the question.

mRNA Limits And A Vaccine Future

Ben Comer 50:00

Excellent. Uh, let's talk a little bit about mRNA, uh, other drug modalities. You know, um, you're uh leading a company called RNA Therapeutics. What do you think needs to happen, Dr. Niazi, for companies to be able to successfully develop and commercialize generic versions of new drug modalities like mRNA therapeutics? Are we in a similar place as we were in 1999 with biosimilars or are we further ahead than that?

Sarfaraz Niazi, Ph.D. 50:31

Wonderful question. And I you and I can talk about like my uh Voice of America uh conference a bit. But so, first of all, um mRNA uh therapeutics, I've uh and I want to share this with anyone who is listening today, okay? Is that FDA will never approve a drug made through mRNA if its dose is critical.

Ben Comer 51:00

Dose is critical?

Sarfaraz Niazi, Ph.D. 51:02

If the see if a dose is important. Oh, okay.

Ben Comer 51:05

I see what you're saying. Yeah.

Sarfaraz Niazi, Ph.D. 51:06

Uh let me tell you, so I filed something and I know exactly what happened, okay? Um, a single molecule of RNA can make a million molecules of the protein with a lot of variability. You can never control it. So if I if I wanted to make say darbepoetin, I cannot make it by mRNA. Unfortunately, billions of dollars are invested today to do exactly that. Um, express antibodies and express proteins by mRNA. I'm telling you.

Ben Comer 51:40

And you're saying you're saying you it's impossible to control the volume of that protein expression.

Sarfaraz Niazi, Ph.D. 51:45

You cannot control the dosing no matter how much you try. It's an innate property. Okay, so I'm telling anybody listening, don't do it.

Ben Comer 51:54

Okay.

Sarfaraz Niazi, Ph.D. 51:54

For vaccine purpose, excellent, because there the dosing is not significantly important. Okay. You know, we had the COVID vaccine. Okay. Uh what we did was we took it to a very different level. Okay. Uh, our first product, which is uh at the initial FDA review, is a generic vaccine against breast cancer. When I say generic, um I realized that if I have to get any drug developed vaccine or otherwise for individual patients, is going to be millions of dollars unaffordable.

Ben Comer 52:36

Right.

Sarfaraz Niazi, Ph.D. 52:37

So what we did was um, and we got some very nice patents also, when there's a breast cancer, there's also mutation of other genes which happens in all breast cancer patients, same gene. So this is there is a generic gene that mutates the same time as the BRIC 2 gene uh mutates. So we took the uh generic gene and made a vaccine against it, okay. So any cell that has a mutated gene because of the breast cancer genes mutation will be uh killed.

Ben Comer 53:20

So is this a bio better? Are you familiar with that phrase?

Sarfaraz Niazi, Ph.D. 53:23

No, no, it's not a bio, it's a bio excellent, okay. I mean, okay, there's not no vaccine today, okay, which is a generic.

Ben Comer 53:33

Oh, yes, right, right.

Sarfaraz Niazi, Ph.D. 53:34

There's no generic yeah again. I I I'm predicting today in your program and your audience done correctly in 10 years, we will not have cancer. 10 years. 10 years. You know why? Let me tell you why, okay. We know what causes cancer, it's a genetic mutation. Okay, it can happen to you, to me, or anybody, okay. Once you know it, okay, you can stop it beforehand. Like our uh breast cancer vaccine uh will be given, not given to all uh girls or women, but if you show Baraka 2 positive, you take this vaccine and you will never get breast cancer, period. When you have a cancer, okay, there are common elements to mutation. So my patterns are not finding what is causing the cancer, but what is causing other genes to mutate when it causes cancer. Okay, so I can now create, I call it a generic uh vaccines. So we uh we have a vaccine against cancer. And are you ready? Against Alzheimer's.

Ben Comer 54:52

Wow, okay.

Sarfaraz Niazi, Ph.D. 54:53

Alzheimer's is a there is a protein coming out, okay. And again, you can go to google.com. I gave you some very valuable information where to find me. Um, you can write it there, okay? mRNA vaccines against uh Alzheimer's. Okay. So now we are looking at an era of dramatic changes in therapies. Dramatic. Okay. And these are much safer medicines to put in there in the body. Much cheaper to make it okay. Because I'm not making a protein, I'm making an mRNA product. I'm putting it into nanoparticles and injecting it. And one of the products which I think should uh make everybody listening to this uh uh meeting happy is that I got a Botox by mRNA in a topical application. Okay, in this universe will carry this cream with her every time she laughs hard, okay, she'll apply right away. Okay, so a lot of future is coming in, okay?

Ben Comer 56:02

But so the the uh the yeah, the few it sounds like you're saying the uh the cure for cancer is prophylactic, is that correct?

Sarfaraz Niazi, Ph.D. 56:10

Well, you you're got it, okay. No, uh let me go back to the word prophylactic, okay. Um, if you know you can prevent something, that's a prophylaxis, okay? Um, but if you know how to stop it, okay, that's the interventional therapy, which is a vaccine. Okay. Um, if there are signs, let's say a person is now diagnosed with uh um liver cancer. Okay, we know which gene it is, okay? All right. How do I kill all those cells that are carrying the gene? Uh one of our products is called uh the CRISPR technology that we're using. Okay. When we go in there, we identify the cell which is bad and just kill it. Okay. So I think uh you will see significant changes coming in, but I don't want anyone wasting time or money in mRNA-based therapeutic delivery because I have already gone to FDA and I'm giving them free advice, okay. They will never approve it. Okay. But mRNA, and then we have uh gene therapy and so many uh other areas are coming up now. And I want companies to invest in those areas, okay, which are much safer to for the investment part of it. Do it, yeah.

Ben Comer 57:30

Well, um, regretfully, I feel like we could go on talking for another hour or at least, Dr. Niazi. But um, I I really appreciate you coming on the show. Uh, it was very interesting. Um, uh, thanks for being here.

Sarfaraz Niazi, Ph.D. 57:44

I'm very pleased to be here, and hello to your audience again.

Ben Comer 57:49

We've been speaking with Sarfaraz Niazi, Ph.D. Uh, he's uh uh CEO at at multiple companies, including RNA Therapeutics, ABYOLO, and Dey Therapeutics. I'm Ben Comer, and you've just listened to the Business of Biotech. Find us and subscribe anywhere you listen to podcasts, and be sure to check out our weekly video cast of these conversations every Monday under the Business of Biotech tab at life science leader.com. We'll see you next week, and thanks as always for listening.