Very bullish for crude oil/SDRL
Novartis’ multiple myeloma drug Farydak and AstraZeneca’s ovarian cancer treatment Lynparza both fared poorly in their visits to the Oncologic Drugs Advisory Committee, yet they gained accelerated approval after the sponsors – at FDA’s urging – revised the indications to make the benefit/risk profile more attractive.
FDA’s recent approval of two oncology drugs demonstrates that a negative advisory committee review does not necessarily mean a new product application is doomed in its first review cycle
Pivotal to the approval of both Novartis AG‘s Farydak (panobinostat) for multiple myeloma andAstraZeneca PLC’s ovarian cancer treatment Lynparza (olaparib) was the sponsors’ ability, with FDA’s urging and support, to identify a narrower subpopulation of patients where the benefit/risk profile was more favorable than the originally proposed indication.
That members of the Oncologic Drugs Advisory Committee believed both drugs had activity in treating the disease at issue – despite recommending against approval for their original indications – also didn’t hurt the sponsors’ chances to reframe their case for approval.
And while the NDA amendments necessitated by the revised indications resulted in extensions to the user fee dates for the drugs, both of which were undergoing priority review, a three-month delay was clearly preferable to the sponsors than a first-cycle “complete response” letter.
As for FDA, although there may be problems with the clinical trials intended to support a sponsor’s original proposed indication, if a compound has activity “it’s incumbent on us” to work with the sponsor to try to get the drug to the public for areas of high unmet medical need, Office of Hematology and Oncology Products Director Richard Pazdur said in an interview.
Yet, 98% of patients enrolled in the Valstar trial that lead to its approval were white. Makes no sense.
In 2013, the FDA had specialists lay out the recommended trial design, and yet the adcom yesterday rejected Telesta's trial as being insufficient?
What is interesting to note is item number 2 below; this points to the difficultly with a double arm trial. Urologists dislike giving Valstar. That leaves practically no options in the BCG refractory setting for the second arm of a clinical trial.
Also note item number 5 below; the committee said a single arm trial could be considered robust if certain response rates were achieved; MCNA met those multi-year response rates!
Clinical Trial Design for the Development of New Therapies for Nonmuscle-invasive Bladder Cancer: Report of a Food and Drug Administration and American Urological Association Public Workshop
To summarize the discussion at a public workshop, cosponsored by the U.S. Food and Drug Administration (FDA) and the American Urological Association, reviewing potential trial designs for the development of new therapies for non–muscle-invasive bladder cancer (NMIBC). There have been only 3 drug approvals for NMIBC in the last 30 years, and product development for this disease has been stymied by difficulties in trial design and patient accrual.
A workshop evaluating potential trial design for the development of therapies for NMIBC was held in San Diego, CA, in May 2013. Invited experts representing all stakeholders, including urology, medical oncology, radiation oncology, industry, and patient advocates, discussed development of products for all risk strata of NMIBC.
Trial Design for Patients With BCG-refractory NMIBC
1) The panel defined BCG-refractory disease as patients who received 2 induction courses of BCG, induction plus maintenance (usually within 6 months), or were intolerant of BCG.5, 6 and 7
2) The panel could not agree on a standard of care for the treatment of these patients to use as a control arm but did agree that additional BCG is not appropriate.
3) There was broad consensus that a placebo arm was inappropriate for ethical and practical reasons.
4) There was discussion by the panel of the use of physician choice for a comparator in a randomized controlled trial in this patient population.
5) There was broad consensus by the panel that provided the results were robust, a single-arm trial could provide sufficient evidence of benefit. For patients with BCG-refractory CIS, the panel felt that an initial complete response rate of 40%-50% at 6 months and a durable response rate of at least 30% for 18-24 months with the lower bound of the 95% confidence interval excluding 20% could be clinically meaningful.8
•There was discussion on how to handle a patient who recurred with low-grade papillary disease and whether to call them a failure without development of a consensus.
• There was no discussion of what would be an acceptable level of response/recurrence-free interval for patients with BCG-refractory papillary disease without CIS.
Philstock, interesting to note that Valstar was also initially rejected by the adcom and only given recommendation after they presented more data.....the adcom approved by only for a restricted "cysectomy rejecting/ineligible population".
I mention this because we would esentially gain approval for the exact same indication that Valstar received, and they were able to do very well sales wise in the US.
Advisory committee initially rejected Valstar as well. When they finally did recommend it they did so with the following caveat:
"In the end, the committee decided the study data failed to support the wisdom of using Valstar as an alternative to cystectomy in patients medically able to undergo the procedure but who refuse to do so. "It voted 9-to-2 with one abstention to approve Valstar only for those patients in whom cystectomy is medically contraindicated."
Three Months After Voting Nay, ODAC Backs Valstar Approval
October 01, 1998
BETHESDA, Md--Three months after refusing to give its blessing to Valstar (valrubicin), the Oncologic Drugs Advisory Committee (ODAC) reheard Anthra Pharmaceuticals new drug application and recommended that the FDA approve the new anthracycline for use in a limited population of patients with carcinoma in situ (CIS) of the urinary bladder.
The panel gave its backing to Valstar for intravesical use in patients who are refractory to BCG immunotherapy and who have a medical contraindication to cystectomy. It refused to endorse the drugs use in BCG-refractory patients who are candidates for cystectomy but who refuse to undergo the surgery. During its presentation, the company had argued that after BCG failure, people who refuse cystectomy and those who cannot undergo the surgery have no effective drug treatment.
Last June, Anthra presented ODAC with combined data from two nonran-domized, open-label phase II studies that involved a total of 90 patients. The trials were identical except for the study sites. Patients were treated with 800 mg of Valstar weekly for 6 weeks in each study.
Anthra claimed complete responses in 19 patients. The FDA staff accepted only 7 of these in its analysis, which the company and its consultants challenged.
ODAC members in June generally found Valstars toxicity acceptable but questioned whether the trial data supported the benefit claimed, because a number of people who didnt respond also did not go on to cystectomy, with no apparent difference in outcome. Several suggested that Anthra might have additional information that would make its case more persuasive.
At the September ODAC meeting, both the company and FDA presented new analyses of the combined studies, A9301 (35 patients) and A9302 (55 patients), that included additional data supplied by Anthra. The company again listed 19 complete responders; the FDA classified 9 patients as comp
Yet Valstar was approved by FDA
Please see below:
Yet the product was approved by the FDA. Just go to the FDA website and check.
I try not to focus on the hour to hour fluctuations, but on the long term picture instead.
This will be a $3.50 per share stock in March if we get FDA approval; it should be 1.50 - 2.00 with positive FDA adcom news on November 18th. This is what I am focused on.
A "buy the rumor, sell the news" type of situation?
No, I am not worried about happening in the case of Telesta. Telesta currently has a market cap of $150M; with FDA approval they should be instantaneously worth $1B based upon conservative sales estimates for MCNA.
If Telesta currently had a market cap of $750M, then yes I would be somewhat concerned about a selloff due to good news already being baked into the current price, but it is not.
That is why biotechs are getting clobbered.