Pharma’s Cutting Edge

It’s about time, but never too late for Sandoz to celebrate the approval of the GH “biosimilar” known as Omnitrope. The CHMP opinion is the required precursor to EC approval. If approved, Omnitrope will be the European Union’s first approval since biosimilar guidelines were issued there over a year ago. In the U.S., Sandoz (parnet Novartis) is suing FDA to advance action on the 505(b)(2) NDA for the drug. FDA guidance for accelerated approval pathways for recombinant drugs is expected later this year.

In case you missed “60 Minutes” last night, they did this story on Hollis-Eden and Project Bioshield, which I ‘ve discussed in these pages previously. As only 60 Minutes can do, they made Stewart Simonson, DHHS’ man in charge of government procurement of medicines to treat the effects of targeted warfare against U.S. cirizens, look like a completely inept, arrogant asshole. Maybe he is. Maybe he isn’t. I don’t know, but I laughed out loud at 60 Minutes caricature of the man. In any case, 60 Minutes made no attempt to describe exactly what Neumune from Hollis-Eden is, how it works, or how effective it is. So, I figured I’d just fill in those blanks.

Neumune is 5-Androsten-3{beta}, 17{beta}-Diol (a.k.a. androstenediol), a steroidal “androstene” metabolically derived from the weak androgen DHEA, that in preclinical studies protects against hematopoetic depletion following radiation and cytotoxic chemotherapy exposure. Beta androstenetriol increases the levels of the TH(1) cytokines, IL-2, IL-3, IFN gamma and counteracts hydrocortisone-mediated immune suppression. Hollis-Eden has exclusive rights to develop the drug from Virginia Commonwealth University (Roger Loria of VCU invented the clinical use). The drug has been studied in Phase 1 clinical trials in humans, preliminary results of which were presented in October 2005. These results indicated that Neumune was well tolerated and was associated with dose-dependent increases in neutrophils and platelets. Phase 2 and 3 clinical trials are not required by FDA for U.S. approval, as they would be unethical for the intended use. Extensive preclinical studies, most of which have not been published in peer-reviewed journals, have demonstrated that Neumune can reduce the incidence and duration of severe neutropenia following systemic radiation exposure and cytotoxic chemotherapy (e.g carboplatin). At ASH 2005, Hollis-Eden presented data from a preclinical meta-analysis, involving 100 non-human primates (rhesus macaques) demonstrating an ~50% decrease in mortality following total body irradiation (42% vs. 22%) and post-exposure treatment with Neumune.

Let’s have a look at newly approved Exubera’s (inhaled rDNA insulin, Pfizer) label. As soon as it’s available publicly, I’ll also review the approved post-marketing safety surveillance and risk management plan, which Pfizer is touting as the new industry standard. To my knowledge, Exubera is the first approved protein therapeutic that is intentionally delivered systemically via the lungs. It replaces/supplements a popular subctaneous-injectable medicine in so doing. For these reasons, it is an important precedent molecule that the biotech community should observe carefully.

The key label provisions of general industry interest are shown below.

Smoking: Exubera is contraindicated in smokers and recent ex-smokers, not because of a risk of lung damage but because of enhanced insulin effects:

“In smokers, the systemic insulin exposure for EXUBERA is expected to be 2 to 5 fold higher than in non-smokers. EXUBERA is contraindicated in patients who smoke or who have discontinued smoking less than 6 months prior to starting EXUBERA therapy. If a patient starts or resumes smoking, EXUBERA must be discontinued immediately due to the increased risk of hypoglycemia, and an alternative treatment must be utilized (see CONTRAINDICATIONS).”

Patients with Underlying Lung Diseases: Unlike the smoking contraindication, lung diseases present a risk to the patient that has not been quantified. Unstable lung disease is a contraindication due to altered absorption of insulin. The average clinician will be confused between a stable and an unstable lung disease, as am I. The risk management program will need to address this source of confusion. Look for this imprecise labeling as a potential area for product liability issues to arise.

“The use of EXUBERA in patients with underlying lung disease, such as asthma or COPD, is not recommended because the safety and efficacy of EXUBERA in this population have not been established (see WARNINGS). The use of EXUBERA is contraindicated in patients with unstable or poorly controlled lung disease, because of wide variations in lung function that could affect the absorption of EXUBERA and increase the risk of hypoglycemia or hyperglycemia (see CONTRAINDICATIONS).”

Effect on Pulmonary Function: All patients require baseline PFTs before starting therapy. I have to wonder how HMOs will view this from a reimbursement perspective. It will depend on whether they view the total cost of Exubera treatment, including screening and follow-up pulmonary testing, as cost-effective. That will depend, in part, on the perceived quality/credibility of Pfizer’s existing cost-effectiveness studies and models. Read the rest of this entry »

Will the Boston Scientific/Guidant/Abbott deal close? The market seems to think there’s a good chance it won’t. If it doesn’t, look for J&J to make a reduced-value offer for Guidant (under $70/share). If it does, look for J&J and Abbott to benefit most (after Guidant stockholders, of course) from the over-priced deal. Boston Scientific shareholders comes out on the losing end of this deal either way in my estimation.

Lots of news out today. As always, I’ll try to pull out the stuff that’s less well covered by the mainstream press. Here’s a very big story developing from the USPTO on a proposed rule that would limit patent follow-on applications to one and claim number to 10. Wow. This would be a huge change of practice to biotech and pharma if implemented as proposed. Read the attached story and watch for the public outcry from industry with a move to the courts to prevent the rule implementation as proposed if necessary.