An FDA advisory committee this week gave a half-hearted vote of approval – 9-8, with two abstentions – for Alexza Pharmaceuticals Inc.’s Adasuve (Staccato loxapine). But the vote was conditioned on limiting the inhaled antipsychotic to one dose per day and imposing a much stiffer REMS than what the company had proposed.
While Alexza didn’t feel that much love from the Psychopharmacologic Drugs Advisory Committee (PDAC), it did get enough to bolster its flailing shares and keep hope alive for FDA approval come the Feb. 4 PDUFA date. A day after the lackluster committee performance, Alexza (NASDAQ:ALXA) hit $1, a 60 percent improvement over its Friday closing of 62.5 cents. But as the day waned and the reality of the vote sank in, the share price settled at just under 80 cents Tuesday.
There may have been a lot more love flowing had Alexza not fallen into a trap that’s ensnaring a lot of promising drugs: It forgot its patient.
In focusing on getting drugs developed and approved by an agency more and more averse to risk, drugmakers often try to create the perfect trial setting to showcase the efficacy and “safety” of their investigational drugs. The trouble is patients don’t live in a perfect world.
The real world setting for Adasuve, for instance, is most likely the psychiatric emergency room, but Alexza didn’t test it there. Instead, it recruited subjects through community referrals. Because of a risk of bronchospasms, trial subjects went through intensive screening for asthma and chronic obstructive pulmonary disease. Those with significant pulmonary disease were excluded from the pivotal trials. Subjects also were trained to use the device prior to treatment.
But when acutely agitated patients are brought in to a psychiatric emergency room, they are in no condition to give their medical history, follow directions on use of an inhaler or effectively report respiratory problems they might have as a result of the treatment.
Another fact Alexza forgot about Adasuve’s intended patients is that they have a high rate of smoking, which can lead to respiratory problems. In testing Adasuve, Alexza excluded smokers, for safety reasons, from its Phase I and II trials. As a result of the trial setting and exclusions, the FDA questioned whether the true risks of Adasuve are known.
To ease the FDA’s concerns, Alexza proposed a real-world postmarket study that would, for the first time, compare Adasuve with standard of care instead of placebo. PDAC members rightly commented that this study should have been done to support approval.
Alexza isn’t alone in forgetting the intended patient in an effort to make a drug as attractive as possible. Time after time, advisory committees question sponsors about the lack of relevant study data. While a sponsor could go broke conducting every study a committee suggests, some of them are no-brainers. An antiviral being developed to treat hepatitis C should be tested in patients who also have HIV since the two are often comorbidities. Or a drug intended mostly for a geriatric population should be tested in elderly subjects instead of younger people who might be healthier.
Yet sponsors continue to come to advisory committees with the answers to the wrong questions, hoping that a REMS, a boxed warning or a restricted label will cover the inadequacies of their trials. Instead, they should begin by focusing on the needs, the health and the lifestyle of the intended patients and then design their trials based on those demographics.
While all you biotechs out there scramble to meet your end-of-year milestones, BioWorld would like to announce a little milestone of our own. That’s right, this is our fifth annual biotech holiday gift guide.
To celebrate five years of excellent gift recommendations for every biotechie on your list – be they scientist, fashionista, bibliophile, new parent, Wall Street exec, traveler, or anyone else – we’re bringing you a Top 10 list of our staff’s all-time favorites. So without further ado:
10. Ever wanted to wash yourself with E. Coli or S. Enteritidis? Now you can, with Petri Dish Soaps, a hand-made coconut oil product colored like the streak patterns of various bacteria on different types of agar.
9. What could be more romantic than carrying a little piece of the one you love with you everywhere you go? That’s what the DNA Life Pendant offers: a tiny silver and glass necklace charm that holds a DNA sample from your loved one.
8. It’s hard to catch a biotech exec without a smart phone in hand. I mean, how else are you expected to stay awake during those endless scientific presentations and board meetings? So consider giving an iTunes gift card for purchasing all the latest apps. Top recommendations from our readers include: Epocrates, Pubmed on Tap, Papers, FDA Drug Approvals, Clinical Trials, NextBio and Byline.
7. If you've got parents-to-be on your holiday list, ask if they're registered at Cord Blood Registry or ViaCord. Banking stem cells from umbilical cord blood can save lives: Around 10,000 cord blood transplants have been performed worldwide to treat dozens of diseases. You can also pick up onesies, bibs and T-shirts proclaiming "there is an exothermic reaction in my diaper" at Clever Cuties.
6. Need to shop for a dog lover? They might appreciate this biotech approach to pinpointing people who don’t pick up after their pooches. BioPet Vet Lab’s Poo-Prints program creates a DNA database for the dogs in your neighborhood, so the next time someone leaves a “deposit” on your lawn, you can mail in a sample and identify the culprit.
5. Nothing says “Happy Holidays” like crochet, but why give a scarf or mittens when you can give a tiny crocheted brain, lungs, pancreas, liver, kidney, eyeball or heart?
4. Why not fill all that wall space in the CEO’s corner office with something really unique? For our 2007 list, BIO President and CEO Jim Greenwood recommended personalized art based on DNA collected with a simple buccal swab.
3. For our 2008 list, Steve Worland, president and CEO of Anadys Pharmaceuticals Inc., suggested companies facilitate their employees' humanitarian efforts with the gift of time. Anadys gave its employees time during the work day to assemble 200 Thanksgiving food baskets for the hungry, a project that Worland noted had "essentially zero cash impact to the company" but hugely impacted employee morale.
2. Got a fashionista on your list? BioWorld Today columnist and biogoddess Cynthia Robbins-Roth suggests jewelry shaped like your favorite molecule (act now, before the folks over at NeurogesX Inc. buy out all of the capsaicin necklaces!).
1. BioWorld Today science editor Anette Breindl recommends Science Tarot, a set of fortune telling cards that blend fine art with hard science. Here’s hoping you draw Mendel’s Peas, which signify growth!