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Expert Financial Analysis and Reporting

Antares: FDA Comments from Type A Meeting Are a Best Case Outcome for Xyosted (ATRS, $2.13, Buy)

Management Comments on Type A Meeting

Antares released the following comment on March 27, 2018 that deals with the Complete Response Letter on Xyosted that was received in October 2017 just before its PDUFA date and necessitated a Type A meeting with the FDA to discuss the CRL. It says.

”Antares Pharma today announced that the official minutes from the Type A meeting with the U.S. Food and Drug Administration (FDA) held on February 21, 2018 have been received. The Company had previously attended the in-person Type A meeting with the FDA to discuss the Complete Response Letter (CRL) received in connection with the XYOSTED™ New Drug Application (NDA).

Based upon this meeting and the FDA minutes, Antares believes that it does not need to conduct any new clinical studies to support the resubmission. The Company anticipates that the submission will include re-analyses of existing data, and address labeling and potential post approval risk mitigation strategies. The Company anticipates submitting the complete response in the second quarter of this year. Under FDA’s policies, thirty days after FDA’s receipt of the resubmission, the Agency will determine whether the filing constitutes a complete response that addresses all deficiencies in the CRL and, if so, assign a target action date which the Company expects will be within six months of FDA’s receipt of the resubmission.”

My Interpretations

  • The single most critical piece of information is that Antares believes it will not need to conduct any more clinical studies to support the resubmission. The requirement for a new trial could have delayed approval for 18 to 24 months. You might ask why the Company didn’t come right out and say that no more trials are needed instead of saying that it believes this to be the case. My interpretation is that FDA indicated to Antares that it would not require a new trial. However, the FDA does not make contractual agreements and always leaves themselves an ability to change their minds. However, there is a very high probability that there will be no new clinical trials required for approval. There might however be the requirement for a post approval study.
  • Re-analysis of existing data is unlikely to be an issue. Usually this deals with the formatting and presentation of data. The FDA has a certain order that it follows as it goes through an NDA and checks off boxes for approval. This should be straightforward.
  • Addressing labeling should also not be an issue. You may recall that Antares said that it was stunned when it received the CRL in October 2017 just before the PDUFA as it was far advanced on labeling discussions and felt things were going well.
  • I asked what risk mitigation strategies might be required and I was told somewhat mysteriously that the Company didn’t want to get into this for competitive reasons. One possibility is that the FDA has been concerned with potential for hypertension and depression with testosterone replacement therapy. It might ask Antares to conduct a post marketing study to see if there is a link. The FDA has asked for such studies from companies with approved products and has been ignored. Xyosted has better pharmacokinetics of any marketed testosterone product and I would expect it to be less causative of side effects related to testosterone replacement. If a post marketing study showed no issue with hypertension and depression Xyosted would be the only product to have demonstrated this. It would be a hugely positive differentiation in the market. It there are issues, it would confirm FDA fears that this is a class effect and Xyosted would not be disadvantaged against other products although the class as a whole might be negatively affected.

Timing of Approval

Antares says that it will resubmit the Complete Response Letter in 2Q, 2018. The FDA will then have 30 days to notify Antares that it has accepted the NDA. Acceptance would indicate that the filing is complete and the probability of approval is high. I expect that this will occur and will be a positive for the stock. According to Antares’s guidance, it will make the submission no later than June (May is possible, April improbable).

Let’s assume that Antares makes the resubmission in June. In July, we will hear if the FDA accepts the filing as complete. If the review is classified as a class I (two month) review from the date when the NDA is resubmitted, the PDUFA date would be September of 2018. If the review is class II (six month review), the PDUFA date would be December of 2018. In my opinion, this should be a class I review, but in dealing with the FDA there is no certainty and the agency is overworked and missing deadline after deadline. Hence, I would bet money that this will be a class II review. This could lead to lead to a January 2019 launch.

Investment Thinking

Whew! This is probably the best outcome that investors could have hoped for. The probability of approval in or before December is quite high and Xyosted is a big opportunity for Antares. This is finally shaping up to be the year of approvals for Antares after frustrating delays on the AB rated generic to EpiPen and Xyosted. AMAG’s Makena auto injector was approved in February and is now being launched; it could be a significant profit opportunity. Also, the AB rated generic to EpiPen should be approved this year although I can’t say when. In late 2017, Teva set an expectation for approval in 1Q, 2018, now it is saying 2018.

There are a plethora of pipeline products beyond these products led by AB rated generics to Byetta and Forteo that will be marketed by Teva. Antares has said that in 2018 it will unveil the next product that it will be developing for its own account like Otrexup and Xyosted. It is also likely working on numerous line extensions with client pharma companies that are being kept close to the vest for competitive reasons.

I am much encouraged with my Buy recommendation.

Possible Explanation for Xyosted CRL

Investors and management were stunned in October 2017 when a Complete Response Letter was received just before Xyosted’s PDUFA date. It is very hard to come up with a reason for the CRL given the excellent clinical data that indicates that Xyosted has the best pharmacokinetics (PK) data of any of the approved gel or injectable testosterone replacement products. Efficacy and minimizing of side effects through better pharmacokinetics is what this class of drugs is all about. Lately, I have heard something that might account for the CRL.

There are two oral testosterone products in late stage clinical development that were due for AdCom meetings in early 2018. These products have more concerning pharmacokinetics and potential side effect issues than Xyosted. On January 9, 2018 an Advisory Committee voting on a recommendation for approval of Clarus Therapeutics Jatenzo split with nine favoring approval and ten against. On January 10, the same AdCom voted six for and thirteen against for approval for Lipocene’s Tlando. Antares has not been asked by the FDA to go before an AdCom suggesting that the FDA is more comfortable with Xyosted. Still, it could have been the case that they wanted to settle questions on the orals before moving ahead on Xyosted and issued the CRL to buy some time. Life and the FDA are not always fair.




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  1. TDPeterson123 says:

    Thanks Larry,

    The outcome, all things considered, could not have been better. It will be interesting to see how the FDA classifies the refiling. If no new data is submitted, it should be a Class I, but until the FDA actually classifies it we won’t know.

    I appreciate that Antares is keeping close to their vest their REMS and possible P4 strategies.

    Your comment of, “It is very hard to come up with a reason for the CRL given the excellent clinical data that indicates that Xyosted has the best pharmacokinetics (PK) data of any of the approved gel or injectable testosterone replacement products.” Focusing on the topic of injectables, per current Symphony data, injected T comprises 66% of all T scripts dispensed, and the trend for injected T continues to show a consistent upward trajectory and velocity for taking market share from the gels. If that trend continues (it’s been on a consistent upward trajectory for the past 3+ years), by year end injected T will be at least 68% of all T scripts dispensed. The PK profile for Xyosted is superior to any T product (gel or otherwise), and especially IM injected T.

    I’m sure there’s more than a few of us who feel the exact same as what you said above, that being, “Whew! This is probably the best outcome that investors could have hoped for. The probability of approval in or before December is quite high and Xyosted is a big opportunity for Antares.”

  2. It does seem that this was the best possible outcome of the meeting. While the market is in a volatile period, especially biotechs, I was still surprised that the stock did not hold the initial gains in reaction to the news. It does seem like a great buying opportunity and I for one did take advantage.

    Can’t find the article, but I did read a publicly distributed note from Zack’s about the Xyosted news which was quite positive. However, in the close the author stated that Zack’s considered Xyosted’s eventual approval a 50/50 proposition. I’m with Larry, but the Zack’s note may be indicative of overall market sentiment.

  3. TDPeterson123 says:

    Wow! That was fast, like two bolts of lightning fast!!. The resubmission of the filing and the FDA’s acceptance of the resubmission occured at warp speed. That tells me that Antares and the FDA are indeed on the same page. Antares knew exactly what they had to resubmit, and the FDA quickly acknowledged receiving exactly what they were expecting to get. And as Larry alluded to, the FDA assigned this with a class 2 response. No surprise there. Does the FDA ever give anything a class 1 response? I did some digging and wasn’t able to find an example. Maybe some are out there, but apparently they’re rare if they do in fact exist.

    EWING, N.J., April 05, 2018 (GLOBE NEWSWIRE) — Antares Pharma, Inc. (ATRS) (the Company) today announced that the U.S. Food and Drug Administration (FDA or the Agency) acknowledged receipt of the Company’s March 29, 2018 resubmission to the Complete Response Letter (CRL) received in connection with the XYOSTED™ (testosterone enanthate subcutaneous injection) New Drug Application. The FDA considered this resubmission a complete, class 2 response and has assigned a user fee goal date of September 29, 2018.

    “We are pleased that the FDA accepted our response to the XYOSTED CRL, and look forward to working closely with the Agency throughout the next review cycle,” said Robert F. Apple, President and Chief Executive Officer of Antares Pharma.

  4. StefanClement says:

    Dear Larry,

    After the quick resubmission of the filing and the FDA’s acceptance of the resubmission I would be very happy to receive a short update from you.

    Unfortunately, the share price has not responded positively to the good news in my view.

    I hope that will change with the daily expected approval of the AB rated generic to EpiPen.

    As for the above points, I have two short questions:

    1. The agency’s action date is September 29. Is there a possibility that the admission may take place sooner or is the date fixed?

    2. Increasingly, I’ve heard about a deal between Mylan and TEVA. TEVA receives money for a delay in EpiPen approval.
    Would that be possible and legally permissible?

    I am looking forward to hearing from you soon.

    Greetings from Germany (Frankfurt)
    Stefan C.

  5. TDPeterson123 says:

    I’m not Larry but I can add a little bit of insight on your questions. The FDA is time and resource strapped. When the FDA sets a PDUFA date, they do well to make that date.

    I don’t see pay for delay at this point between Mylan and Teva for gx epipen. Hatch Waxman paragraph IV patent settlement dates have been characterized as “pay to delay” dates. That agreed upon date was in June 2015 when the key epipen patents expired. At this point, getting that drug approved is really on the FDA and how motivated they are to get this filing approved. Teva says they’ve done everything the FDA has asked them to do.

  6. StefanClement says:

    Thank you!

    Stefan C.


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