NorthWest Biotherapeutics Inc (NWBO)

[Pyrrhonian]

Sad day for DNDN, but can't say we didn't all see it coming. Though what could any Co do in the face of such aggressive competition, with a cheaper, easier to administer, slightly more effective drug? I actually would have shorted DNDN around $3 if I didn't have reservations about the practice (in biotech, that is--I'll short that pig LNKD all day ;) ). To reiterate what most of us here know:

Provenge (from DNDN) showed an improvement over placebo of 4.1 months OS in its approval trial. Of course, that would have made it the new SOC in the metastatic castration resistance prostate cancer space, if it wasn't for the 600% cheaper, far more aggressively marketed Zytiga (abiraterone acetate). Johnson and Johnson received approval for Zytiga around the same time as Provenge, but their data showed it actually edged out Provenge in improving OS:

A pre-specified interim overall survival (OS) analysis was performed when 552 events had occurred. This analysis demonstrated a statistically significant improvement in OS in patients receiving abiraterone acetate compared with patients who received the placebo. (HR = 0.646; 95 percent CI: 0.543, 0.768; p 0.0001). The median OS was 14.8 months for patients who received abiraterone acetate compared with 10.9 months OS for patients who received the placebo. An updated OS analysis, conducted after 775 events, demonstrated a median OS of 15.8 months for patients who received abiraterone acetate compared with 11.2 months for patients who received the placebo (HR = 0.740; 95 percent CI: 0.638, 0.859).

Zytiga showed 4.6 months improvement in OS. Really, what more is there to say? It doesn't require leukapheresis (much easier to administer), it doesn't cost $93K for three months of tx like Provenge, it's sponsored and heavily marketed by JnJ, and most importantly, is more effective than Provenge. Most insurers won't even subsidize the latter as a result, while Zytiga is forecast to earn over $2B in sales next year (2015).

Now, if instead Provenge showed 10 or 12 months OS over control, very few would choose Zytiga.

Comparing Provenge to DCVax-L (from NWBO), however, is a faulty one on various levels, the most important one being potential competition--but let's start with the effectiveness of the two therapies:

In NWBO's Phase I/II multi-center clinical trial in late stage, metastatic prostate cancer, DCVax-Prostate added 18 months of patient survival (to reach overall survival of 38.7 months). NW uses a different approach to loaded the DC's that provided far better efficacy in a clinical setting.

Provenge adds 4.1 months, Zytiga adds 4.5 months--DCVax-Prostate adds 18 months OS.

How about cost?

NWBO's DCVax will be priced in the range of $37,000 per year for up to 3 years of treatment. The pricing of DCVax will also be substantially below the price range of most antibody drugs and "targeted" drugs for cancer. Such drugs are typically priced at $60,000-80,000 per year, and can exceed $100,000 per year. Such drugs also carry significant side effects, and often only extend survival for as little as 10 weeks. The key to the substantial pricing advantage of DCVax is NWBO's proprietary batch manufacturing process together with its cryopreservation technology for frozen storage of the finished vaccine.

In that regard it's not only much cheaper than Provenge, but it's nearly half as expensive as Zytiga, which costs around $5K/month (DCVax would cost around $3K/month on average).

DCVax-Prostate is approved for a 600+ patient, Ph III trial. However, as the space is so crowded, with other novel therapies on the horizon looking to soon enter it, they have focused primarily on the GBM space, where there is literally no competition on the horizon with therapies to treat the entire ND-GBM population. Also, DCVax-L has been granted orphan drug status in the US and EU, which carries 7 and 10 years of marketing exclusivity respectively. In other words, there won't be any competition to deal with from like vaccines should they even reach the space during DCVax-L's potential "tenure."

There have also been no significant advances in treatments in the last 10 years in the GBM space--and that, Temodar, again only increased OS by 2.6 months. The public has been desperate for any advancement in therapy for decades now. Anecdotal studies and early clinical data suggest that DCVax-L may increase patient's lives by almost 2 years on average.

As you can see, comparisons drawn between DCVax-L and Provenge are faulty, and therefore any negative sentiment derived from these comparisons is misplaced. Though I'm sure by this point very few are lumping them together anymore.