This past week, the FDA told Santarus, Inc. that it was extending the review period for their ulcerative colitis drug UCERIS by 3 months. The FDA extended the PDUFA Date to January 16, 2013 because they need more time to complete the review.
I usually don’t comment on share price or share price moves but I’m making an exception here. The stock dipped on this news. I can’t figure these things out. It might not be negative news. I don’t think the FDA has a mind set that says “This application won’t be approved but we need more time to review the bad data”. I think the contrary holds. If the FDA sees some merit in an application, it will take the extra time to support the approval. There is still a PDUFA report card and extending the review period for a drug that will eventually be rejected doesn’t make sense.
The FDA approved QSYMIA, the Vivus compound for the treatment of obesity. As regular readers of this site will know, I have been opining for many months that I didn’t think this would happen soon, if at all.
There has never been a doubt in anyone’s mind that QSYMIA (nee QNEXA) was the most effective of the diet drugs that have been submitted to the FDA. The issue has always been safety. For some it was the cardiovascular risk particularly in light of the recent negative experience with fen-phen. For others, it was the potential for neurological problems. While a concern, I never felt these potential problems would be the obstacle to approval. For me, it was the fact that this was an acknowledged teratogen and a large part of the population of patients who would use this drug would be women of child bearing potential.
The basis for my concern goes back to the very foundation of the modern FDA concern for safety. The Food and Drug Amendments of 1962 were a response to the thalidomide tragedy in Europe. The US was spared because the drug was not approved here. The 1962 Amendments were enacted to prevent such a tragedy from happening here. Some have said that since that time, the FDA has overemphasized safety, often criticized for keeping life saving drugs off the market because of a potential for harm. With the approval of QSYMIA, those critics are silenced – for now.
My webmaster is really excited these days. He just looked at the numbers for June and the number of visitors we had for the month is incredible. He also tells me that he has been receiving a large number of requests, some very specific, about QNEXA probability of approval.
We started this website 2 years ago with the idea that we would provide information free of charge for a while to see if there was any interest, determine what specific information our audience wanted and establish some credibility before deciding if we wanted to commercialize the website. We’ve far exceeded our 3 goals as measured by visitors and feedback. Unfortunately, we weren’t able to convince any of you to purchase a subscription when we offered and just a few lucky folks have purchased our special reports, thus making the business part of this venture a disappointment. This is especially disappointing in light of the number of specific, very detailed requests we are getting for additional information that will be used to make decisions that will make you and your clients a lot of money.
If you have questions about QNEXA, I refer you to our website archives or invite you to purchase our special diet report. I will not be adding any additional comments on the website.
If you still have questions, please consider scheduling a personal discussion. The fee for such consultation is $100 per quarter hour.
My webmaster tells me that we have had a record number of visitors to our website this week. Thank you all for visiting us. I suspect many of you were looking for some last minute comments before the June 27, 2011 PDUFA Date for lorcaserin. I didn’t post anything because I had nothing new to add. As I had said in the past, I thought Arena (ARNA) had a better chance of getting approval for LORQESS than did Qnexa because the cardiac problems could be monitored and managed while the teratogenicity issue with Qnexa was binary, ie, all or nothing on the teratogenic effect.
Well, Arena is rejoicing and ringing the BELVIQ! (nee LORQESS). The folks at Vivus (VVUS) and probably some of the analysts are seeing the BELVIQ approval as a sure sign that an approval for QNEXA is just around the corner. I say not so fast. If you remember, a major concern expressed here and raised by some at the Advisory Committee meeting was whether women of child bearing potential who were overweight would heed the warning to avoid getting pregnant, especially in light of the number of women in the QNEXA controlled clinical trials who became pregnant.
Well, those clever folks at FDA added a couple of things to the BELVIQ approval that might do two things. The first is a warning that women of child bearing potential should not take BELVIQ. If I were FDA, I’d try and find a way to monitor how many women and their physicians paid attention to that warning. Should be relatively easy to collect that information. If they find a significant pregnancy rate in women taking BELVIQ, they know the warning is not enough – all this done without jeopardizing an unborn child. The second thing that the FDA did was to recommend that the DEA assign a control classification to BELVIQ. Whether the DEA will do this is unknown at this time. If they do, there is a made to order distribution control for QNEXA should they decide to do it.
If your looking for the bottom line that I normally provide, this is it – if I had to lose 40 pounds in 2 years and had only the choice of waiting for QNEXA or diet, I’d start giving up the cupcakes tomorrow!
Those of you who read our Special Report on Diet Drugs got a heads up on both the extension of the QNEXA PDUFA Date and the easy time that LORQESS had with the FDA Advisory Committee last week. But now it’s crunch time and the folks at Vivus and Arena Pharmaceuticals are supplementing their diets with fingernail sandwiches. Arena has the shorter wait at this time, June 27, 2012 is still their PDUFA Date for LORQESS. By virtue of the extension, Vivus has to wait until July 26, 2012.
Neither the FDA nor the Advisory Committees have questioned the efficacy of either drug. Neither set of reviewers have tried to say one is more efficacious than the other. I agree and would call them equally efficacious.
Both drugs have reported or perceived cardiovascular side effects. According to the Advisory Committee earlier this year, such drugs should be required to have cardiovascular studies performed before approval. However, both drugs were submitted for approval and under review when the recommendation, and it is only a recommendation, by the Advisory Committee was made. That being said, the FDA has a certain degree of leeway in forcing this requirement as an approval requirement. In my opinion, the FDA will give both companies a break and allow the required study to be done as a condition of approval. It will be the most closely watched event since the OJ trial. One might think that QNEXA has the leg up on this because they went to the Advisory Committee first, but in this case, one would be wrong. Both companies got the information at the same time – from listening to the Advisory Committee live and in person. Who has the edge on having the protocol in final form? I don’t know and neither does anyone else except maybe the FDA and I heard they ain’t talking.
FDA doesn’t have to talk about the cardiovascular protocol race because the race isn’t about the cardiovascular side effects, its about the teratogenicity risk. FDA is breathing a sigh of relief with the data from Arena and the positive vote from the Advisory Committee for LORQESS. The pressure is off – they have a viable diet drug alternative to QNEXA to satisfy those screaming for a new drug. And they have an alternative that is not a teratogen. Even if LORQESS gets an extension of the PDUFA Date from FDA to tidy up their cardiovascular study protocol, they will still be ahead of Vivus who has a somewhat longer struggle with the teratogencity issue.
With the Vivus‘ QNEXA PDUFA scheduled for April 17,2012, we have created a special report that reexamines all of the obesity drugs that have been reviewed by the FDA and the Advisory Committee since 2009 to determine if any additional insight could be gained regarding the expected action the FDA will take on QNEXA. The report can be purchased by clicking here or by going to http://www.pdufadate.com/premium-reports.
We changed our automated delivery method with the NORTHERA report so when you do purchase the Diet Drug Special Report, please make sure your spam filter accepts email from pdufadate.com.
On April 5, 2012, the FDA Reproductive Health Drug Advisory Committee will discuss the mirabegron application from Astellas for the treatment of overactive bladder. Astellas already has a drug on the market for this indication, VESIcare.
The FDA Briefing Document notes that the drug achieved statistical significance in all 3 of the Phase 3 trials submitted and the secondary efficacy endpoints were consistent with efficacy.
Regarding the safety of mirabegron, the FDA has raised several concerns. There is an increase in both heart rate and blood pressure noted in both Phase 1 and Phase 3 trials that seems to be greater with higher doses. The FDA further states that the size of the data base (presumably too small) prevents them from further evaluation of this observation so the question remains open. They also note an increase in neoplasms but this is probably not an issue as they seem to occur at high doses and seem to consist of neoplasm common to adults. Hepatotoxicity, hypersensitivity and urinary tract infections are also noted but are infrequent and probably not an issue either.
This leaves only the cardiovascular safety issues that should be a concern when considering the benefit risk for this product. How will the Advisory Committee respond to the FDA question regarding benefit risk for this product?
We think there will be a positive vote but it will be close. Why? While the efficacy is positive using the statistical significance measure, the clinical significance of the improvement seems marginal. In fact, if one compares the numbers reported by Astellas in the VESIcare package insert, it appears that mirabegron has slightly inferior efficacy. There are patients who should not take VESIcare that seem to be indicated for mirabegron, so the Urologists on the Advisory Committee may see this as a necessary drug for those patients. The big issue will really be how seriously the FDA takes the cardiovascular risks and how the Advisory Committee responds to those concerns.
It will be close, but we think the Advisory Committee will recommend approval.
Correction to this Post.
The comments from our previous post earlier today may have been misunderstood. The post may be incorrectly giving investors the impression that Navidea Biopharmaceuticals, Inc. has not been given an “official” PDUFA date. They have indeed been given a firm PDUFA date. That date per the FDA’s official correspondence to the Company is June 10, 2012. This is the date they have disclosed in their press releases and SEC filings and it is official. However, as previously noted, June 10th is a Sunday. It is understood that is that this date is calculated based on 10 months from the date the NDA was accepted, August 10, 2011. As far as the actual “date”, it is unclear in this case since the PDUFA date falls on a Sunday whether or not the FDA would communicate the NDA status to Navidea before the weekend or on the next business day.
Original Post: Brent Larson, CFO of Navidea Biopharmaceuticals, Inc. (NAVB), told me today that they have not yet received a firm date from the FDA for the company’s PDUFA Date regarding Lymphoseek (Tilmanocept). There has been confusion because the FDA issued a June 10, 2012 date in a letter to the company. This date has been used in company press releases and its Form 10-k.
June 10, 2012 is a Sunday.
The company is hoping the actual PDUFA Date is close to the original date provided by the FDA. Past experience has shown the probable PDUFA Date will be the Friday before the intended date.
On Tuesday, March 20, 2012 the FDA Oncology Drugs Advisory Committee will discuss the supplemental application for GSK‘s VOTRIENT (pazopanib) to use in the treatment of patients with advanced soft tissue sarcoma.
On it’s own, this drug would probably not get a favorable recommendation from the Advisory Committee because the FDA Briefing Document challenges the clinically meaningfulness of the results on PFS and OS. However, when compared to the results they will have also reviewed for the Merck product for the afternoon session, these results will seem quite impressive in the same indication, ie, a three fold improvement in PFS and a 20% improvement in OS. We think this will get a positive endorsement from the Advisory Committee.
On Tuesday, March 20, 2012, the FDA Oncology Drug Advisory Committee will discuss the Merck and Ariad‘s application for TALTORIC (ridaforolimus) in the treatment of metastatic soft tissue sarcoma and bone sarcoma.
This has to be one of the shortest Briefing Documents ever prepared by the FDA for an Advisory Committee Meeting, and rightly so. There are just not that many good things to say about this drug.
The company tried to convince the FDA that PFS was an adequate surrogate for OS. The FDA wasn’t convinced but they agreed in a Special Protocol Assessment to an improvement over placebo control of 25% The company failed to meet this hurdle with only a very small numerical improvement that failed the agreed statistical mark, is of questionable clinical significance and failed to achieve the expected target even for placebo of 6 months of PFS. Match this non-significant improvement against the adverse experience profile and it’s impossible to see how this drug can be viewed as having a positive benefit risk.