Vion Pharmaceuticals' Onrigin: Good Chance of FDA Approval

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 |  Includes: SNY, VION
by: R. Saito

Vion Pharmaceuticals’ (OTC:VION) Onrigin is a single agent drug for remission induction treatment for patients sixty years of age or older with de novo poor-risk acute myeloid leukemia (AML). Onrigin is up for review by the FDA’s oncology drug advisory committee (ODAC) on September 1st, and the market has yet to take notice.

Most analysts have written off Vion’s chances of an approval for Onrigin, mainly due to the following two facts:

  1. The FDA accepted the new drug application (NDA) and issued a standard review with a PDUFA action date of December 12, as opposed to a priority review (generally given to priority and orphan drugs.)
  2. The NDA is based on data from two phase II clinical trials, as opposed to phase III clinical data.

Let’s defuse these two right off the bat. The FDA sees many NDAs and always follows its own guidance for industry for the indication. A quick read of the FDA’s guidance for acute myeloid leukemia reveals the following two statements:

The Agency has accepted durable responses in hematologic malignancies for approval for both chronic leukemias (accelerated approval) and acute leukemias (regular approval).

[...]

For the approval of selected agents in acute leukemia, FDA has accepted durable complete remissions (CR) in single arm trials as evidence of clinical benefit. A substantial and durable CR rate in acute leukemia is generally associated with survival improvements and reductions in infections and blood product use.

So it is clear that the company expected a standard review - and also that the norm for acute myeloid leukemia applications is data from phase II trials. Digging through older ODAC meetings on leukemia confirms this.

As for the standard review period, I will have to guess that this is due to the FDA lacking expertise in AML and having to rely heavily on consulting oncologists to prepare for the review.

In the case of this ODAC meeting, the main expert consultant and also a temporary voting member of the committee is Dr. Gail Roboz, MD; her vote will be counted first on all points. The ODAC will vote on Vion’s Onrigin and Genzyme’s (GENZ) Clolar on the same day - for the same indication.

These drugs are no stranger to Dr. Roboz, as she is currently a primary investigator for a Genzyme Clolar clinical trial and has in the past been a co-investigator on a Vion Onrigin clinical trial, the same trial used as partial data (55 patients in a subgroup) for the current application.

The last time the ODAC voted on a drug for this indication was in May of 2005, when the committee voted 7 against and 4 for Zarnestra. A quick analysis of the data presented shows that the CR rate and survival benefits of Zarnestra were barely above the baseline, with unacceptable toxicity issues and a high 30-day mortality rate in the patient group. Both Onrigin and Clolar show much better response rates and lower toxicities, so we have indeed come a long way in four years.

Central to the May 2005 ODAC meeting was Dr. Susan O’Brien, MD. She was the primary voting member and consultant to the FDA for this meeting, and voted against approval. Dr. O’Brien is the primary investigator for Vion’s trial and has been instrumental in Vion’s preparation of the current NDA. She has worked with Dr. Roboz with this and other leukemia drugs. I expect she will present data to the ODAC on behalf of Vion during the meeting on September 1st.

Observers have noted that Vion’s patient group for the trials backing the NDA are at the very low end of health, while Genzyme is including healthier subjects in their trial. I have not been able to confirm this, as Genzyme does not publish enough detail for a direct comparison. If true, the FDA will most likely take note and will possibly remove data points and run its own tally of CR rate and 30-day mortality rate.

In any case, I expect a positive recommendation from the ODAC for both applications; this patient group is generally left out of regular treatment because they do not see a benefit from the 7/3 regimen. So it will be up to the healthcare system to settle on a standard of care with a choice of a single infusion of Vion’s Onrigin, or five consecutive days of Clolar infusion per treatment.

Both will be required to collect post-market data to substantiate the filing, and I estimate the benefits of both treatments will be about equal with more data.

Vion’s stock price has taken a beating after they stopped a phase III trial of Onrigin in combination with ARA-C. This trial was halted due to a higher induction mortality rate in the treatment arm, and the company has since shown that the toxicity was mainly due to the combination and dosing.

Further analysis of the data from the trial has shown a clear survival advantage in the treatment arm, and the FDA has approved a restart of the trial. Vion’s stock price has not recovered though, and they have even gone through a reverse split in attempts to remain listed on Nasdaq.

Currently, the company has a market cap of $30M and enough cash to survive through Q2 of 2010. The company has a favorable debt structure in the form of a convertible loan with interest only payments, and a conversion to stock in 2012. After the reverse split, the dilution from this loan will be minimal, and one would hope for the sake of the creditors that the PPS is back above $20 at the time of the conversion, this will hinge on the recommendation of the ODAC on September 1st.

Vion’s stock is vastly undervalued going into the advisory committee. A recommendation from the committee will undoubtedly send their shares rocketing back to the levels seen before the Onrigin trial halt. There is a very small community of oncologists dealing with leukemia, and among them, this application is highly anticipated.

As for Genzyme’s Clolar, we will just have to see how the FDA treats their patient selection for the trial. Clolar was rejected by the ODAC for pediatric AML back in 2004 because there was not enough data to show a benefit. I expect both applications will receive a positive recommendation from the ODAC this time around.

Disclosure: Long VION