Drug Candidates to Watch (or not)

Thompson Reuters has come out with a review of what it considers the most promising drug candidates in clinical trials. Although definitions of “promising” may differ (projected sales? impact on patients? innovative approach?) the research firm thinks that cancer drugs and therapeutics that address small patient populations–so called “orphan” indications–are particularly interesting. We’ll leave you to take a look at the Phase III and launched drug lists yourselves, and instead peruse the research firm’s choices for the most intriguing treatments in early-stage studies.

Without further ado, here’s what they’re keeping an eye on from the Phase II category:

1. ALKS-33: an alcohol addiction treatment from Alkermes

2. Recombinant PEG-interferon lambda-1: Hepatitis C treatment being co-developed by ZymoGenetics and Bristol-Myers Squibb.

3. PHA-848125: small molecule for the treatment of thymic cancer by Nerviano Medical Sciences

4. PCI-27483: a small molecule for the treatment of pancreatic cancer by Pharmacyclics

5. SBI-087: an antibody treatment for rheumatoid arthritis that Pfizer inherited from Wyeth, which in turn had licensed from Trubion Pharmaceuticals

Some thoughts on their Phase II list. First, unsurprisingly, two out of the five picks are oncology drugs. Second, chemistry isn’t dead: three out of the five candidates are small molecules. Last, both of the biologics are quasi-next-generation versions of existing drugs. BMS and Zymogenics’ pegylated lambda-interferon is an alternative to pegylated alpha-interferon (see our coverage of the alternative interferon space here), while SBI-087 is going after CD-20, the same target as Biogen Idec and Genentech’s Rituxan.

I’m perplexed at how one winnows out what the most promising Phase I candidates are, but of note is that there’s only one small molecule and one cancer drug candidate on this list. Here’s what Thompson Reuters is giving a shout out to from the earlier reaches of the pipeline:

1. Ad4-H5-Vtn: an avian flu virus vaccine by PaxVax

2. Adoptive T-cell therapy: an HIV treatment by Adaptimmune

3. BI-505: antibody to treat multiple myeloma by BioInvent

4. CHF-5074: a small molecule to treat Alzheimer’s disease by Chiesi

5. sFLT-01: gene therapy for wet age-related macular degeneration by Genzyme and Applied Genetic Technologies

I will quibble with the choice of Chiesi’s Alzheimer’s drug, which combines a flurbiprofen analog (an anti-inflammatory agent) and a gamma-secretase inhibitor. Several big pharma firms have been working for years on molecules to block gamma-secretase, an enzyme that enables the formation of beta-amyloid, the main component of the plaque gumming up the brains of Alzheimer’s patients. Many of those compounds are already in late-stage trials, including one by Bristol-Myers Squibb that is exquisitely selective and potent. I’d be more impressed if Chiesi had a compound that blocks beta-secretase (the other enzyme critical in beta-amyloid formation) in Phase I, as that target has been tougher to crack. Further, as we wrote this spring, the beta-amyloid hypothesis is, well, still a hypothesis. Despite the correlation between brain plaque and disease, not everyone is convinced that beta-amyloid actually causes the disease. Some evidence has emerged to suggest overproduction of the protein could actually be the body’s way of combating an infection. Though this drug candidate does combine the gamma-secretase with the anti-inflammatory component, it still feels like an odd choice. My feeling is if you’re going to pick a compound that stands out from the gigantic Phase I crowd, going with a well-trodden target doesn’t entirely make sense. Perhaps readers will have some insight that will change my mind.

That said, the PaxVax candidate is an intriguing choice. The company claims to have come up with a way to enable oral delivery of vaccines, which would be great for stability and portability.

So dear readers, what do you think? A good list? Which candidates would you add?

Author: Lisa Jarvis

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