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In the July 2012 earnings conference call, Questcor's Chief Scientific Officer gave a good summary of the chances of a generic version of Acthar arising. He characterized the process of producing a generic as very challenging and provided his reasoning. He specifically mentioned Synacthen towards the end and said that even if Novartis manages to clear a bunch of hurdles to get it approved by the FDA, it still would only be approved for one indication (Questcor's Acthar is approved for 19 indications).

It is good reading, and if true, the reasoning alleviates my fears that a generic will emerge anytime soon. It's always a risk, but that risk seems to be small.

And going backwards a bit, Synacthen contains benzyl alcohol, which is toxic to children and can be fatal. It would face substantial scrutiny for use for infantile spasms.


At a recent investor conference, I addressed the question whether old ACTH applications or NDA and ANDA might be revived without doing any additional research, based on our understanding of the drug products, our in-depth understanding of FDA requirements and our experience with both the offices of new drugs and the office of generic drugs at the FDA. It is our belief that the NDA and ANDA cannot be reinstated without the significant amount of work. All of the old NDAs have been discontinued. It is our understanding that any company attempting to reintroduce them to the public will be required to submit either a brand new product application following the manufacturing efficacy and safety standards today or they could request reinstatement after first meeting moderate FDA manufacturing and efficacy and safety standards.

We believe that either approach would require FDA approved manufacturing facilities and processes, toxicology programs, and clinical efficacy and safety data for each desired indication. Essentially, this would be a program not unlike when required for new chemical entity, we are not aware of any effort to reinstate these old NDAs. It is our estimate that such a program would carry significant risk and require many years to prepare an FDA submission. To compete with Acthar Gel, the product may also have to be compared head-to-head with our Acthar Gel in trial this would impact the chances of success in the clinical trial.

We have also been asked a number of questions about the generic, the purchase of Watson Generic. The Watson Generic is not a generic of Questcor’s HP Acthar Gel nor any modified release form of ACTH. There are no generics of Acthar Gel that exists to our knowledge. Therefore, there should be a little, where no threat of a substitutable generic product from these previously approved discontinued products. Many of the old products including the Watson Generic appear to have used an immediate release powder version of pituitary extract, not Questcor’s long-acting Acthar Gel. The immediate release powder for a very short-acting and is metabolized within minutes, which is conducive to diagnostic use, but would likely not be the sort of the therapeutic drug. Even if an immediate release powder form of Acthar will be reproduced following today’s manufacturing standards, which we do believe would be very challenging.

Manufacturing Acthar Gel involves several complex process and steps versus just mixing gels in with the porcine pituitary extract that is done with the Watson product. The competitive hurdles are highest for potential AB rated generic version of the Acthar. We continue to believe that any potential generic competitor will have multiple challenges.

First, a generic without difficulty characterizing all of the active peptides in Acthar Gel, given the final product in a gel made of peptide and the final peptide profile is very dependent on the manufacturing steps, including the pituitary extraction. Their characterization of active peptides is a requirement for generic. Two, the manufacturing process is not public information. Three, our pituitary extracted Acthar is now available to any of the source. Four, based on our understanding of the FDA generic guidance, the generic drug will be required to demonstrate chemical equivalents and bioequivalent, Acthar Gel in order to ensure the same safety and efficacy profile. Given the challenges one, two, three that I mentioned above, developing a product can be shown to the both chemical equivalent and bioequivalent is very challenging.

From a regulatory perspective, Acthar Gel appears to be very similar to Premarin, which is a hormone replacement therapy derived from the urine of pregnant mares and contains many different estrogens. Premarin was approved by the FDA in 1942 and then has never been a generic approved. Like Acthar Gel, the precise knowledge of the composition of Premarin and as each of the various estrogens contributes to the drug’s overall effectiveness has never been definitively determined.

Generic companies that try to copy the Premarin production process were not successful. They also attempted to make synthetic generic versions of Premarin. But in 1997, the FDA decided not to approve those synthetic generic forms of Premarin because they were not shown to contain the exact same type of ingredients and therefore the therapeutic equivalents could not be proven through the generic drug approval process.

Similar to Premarin, Acthar Gel would be extremely difficult to copy. A generic Acthar Gel has never been approved by FDA and the development and approval of a generic Acthar Gel is extremely unlikely. We have long held and noted that creating a competitive ACTH product certainly a possibility. However, approval would required a new drug application, which would likely require a full toxicology program together with the four clinical program demonstrate efficacy and safety for each desired indication.

Our belief is that this will take a minimum of five years and we are not aware of any effort underway. If an asset grew underway in U.S, it would likely be registered on In addition, the label for Acthar notes that Acthar is reported to bind to melanocortin receptors plural receptors. This probably eliminates the possibility of these in cortisol as a surrogate for clinical end points of Acthar Gel efficacy since introduced to only one of the bioequivalent receptors.

Since different melanocortin receptors are known to act on different body systems, we believe applications – applicants would only receive approvals for the specific indication investigated in the clinical efficacy and safety settings of the regulatory filing. With respect to Synacthen, a synthetic peptide marketed by Novartis in Europe and Australia. We believe unlikely to be compared to Acthar. Synacthen is a fragment of ACTH called tetracosactide and is not an androgynous peptide of the body.

It has the different amino acid sequence and a different pharmacology profile from Acthar Gel. Synacthen contains benzyl alcohol, which is toxic to children, it can potentially cause gastric syndrome, it can be fatal.

Since Acthar Gel is widely used in children under two years of age for infantile spasm, Synacthen might face substantial safety and distribution issues in U.S. In addition, Synacthen will face the same regulatory and business issues discussed earlier for similar ACTH vials. All said the company plans to reinstate to old NDA for developing a similar ACTH product like Acthar, that company will have to weigh the time and cost for development, the regulatory hurdles and market value potential indication and likely sales promotion costs, the short three to five year exclusivity period unless (indiscernible) with lower penetration and then decide whether it’s worthwhile to develop a competing product to Acthar Gel.

And even if they decided to move forward, all this would result in a proven only one indication. Others have estimated that Acthar Gel markets for the single indication will need to be in the $800 million to $1 billion range in order to make the efforts financially viable option. Furthermore, we believe that ACTH product previously approved would not likely become competitors to Acthar Gel, anytime soon either because the lack of therapeutic usefulness and or regulations required compliance with modern manufacturing, safety, and efficacy patterns.

Finally, Synacthen by our analysis faces substantial approval hurdles as well. When compared to generic drug, we believe that in generic drug approval is unlikely due to this complexity involved, improving similarities to Acthar Gel.
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