By Jim Shrine

Alkermes Inc. stopped a Phase III trial of Cereport and carboplatin in newly diagnosed brain tumor patients, because flaws in the study design led company officials to conclude it would not be completed successfully.

CEO Richard Pops said the study, started in March 1998, suffered from difficulty in patient enrollment, stringent enrollment criteria that led to a non-representative patient population, and a complicated protocol that required significant commitments from physicians and patients.

Cereport (formerly called RMP-7) is a bradykinin analogue designed to help carry compounds across the blood-brain barrier by transiently increasing its permeability. Two other Phase II trials of Cereport and the chemotherapy agent carboplatin are ongoing.

¿The mistake many biotech companies make,¿ Pops said, ¿is they resist stopping studies that aren¿t enrolling well or where the design is not appropriate because they worry about the impact on the company. We have so many programs that we¿re free to make decisions based on which programs are performing. Our willingness to terminate this particular protocol is indicative that this protocol is not appropriate ¿ not whether Cereport is a viable candidate.¿

The ongoing Phase II studies, along with partner Alza Corp., will go a long way toward determining the value of the Cereport program. One Phase II is in adult patients with brain metastases from lung cancer. A component of that study is testing whether significantly increased doses lead to more robust responses. That is expected to be completed around mid-year, Pops said. The other Phase II, being conducted by the National Cancer Institute, is in pediatric patients with brain tumors.

The Phase III trial was Alkermes¿ first in newly diagnosed brain cancer patients, a much narrower indication than metastatic disease.

¿The main commercial focus of the program since the time of our collaboration with Alza has been in metastatic brain tumors, which have spread to the brain from other sites of origin,¿ Pops said.

Alza, of Palo Alto, Calif., and Alkermes, of Cambridge, Mass., entered into an option agreement on Cereport in October 1997. Alza paid $10 million up front for that option and will have to decide after the Phase II studies whether it wants to continue. If so, Alza would pay Alkermes up to $30 million to fund additional trials, and $20 million in post-launch milestones. Then, the companies would share profits.

Investors have not attached significant value to Cereport relative to Alkermes¿ other programs, Pops said.

That fact, together with the more significant trials in metastatic disease, might explain the small drop in the company¿s value following the Phase III failure. Alkermes (NASDAQ:ALKS) lost $1.875, or more than 6 percent, Wednesday to close at $26.688.

In the Phase III trial, patients with glioblastoma multiforme, a high-grade tumor, had surgical resection of the tumor. Then, they received carboplatin and placebo or carboplatin and Cereport, prior to radiotherapy. The standard care for this indication is surgery, followed by radiotherapy. Patients in the study will have the option to continue their treatment as called for in the protocol, and at the investigator¿s discretion.

Medisorb Phase III To Begin This Year

Alkermes has a variety of other drug-delivery technologies in development. The lead ones are ProLease and Medisorb, for the sustained release of injectable drugs.

Alkermes and Genentech Inc., of South San Francisco, are using ProLease to deliver human growth hormone in a product called Nutropin Depot. A new drug application is expected to be filed soon, Pops said. Alkermes and Johnson & Johnson (J&J), of New Brunswick, N.J., have completed safety studies using ProLease to deliver erythropoietin.

One application of Medisorb is being developed with a J&J subsidiary in an undisclosed therapeutic area, in which a Phase III trial is expected to begin this year, Pops said.

Alkermes recently added technology for delivering small molecules to the lung for respiratory diseases and for delivering large molecules via the lung, through a $114 million stock acquisition of Advanced Inhalation Research Inc., of Cambridge, Mass. Pops said that technology is in the clinic, testing sustained-release formulations of albuterol for asthma and estrogen for post-menopausal conditions. (See BioWorld Today, Feb. 2, 1999, p. 1.)

The other delivery platforms are RingCap and Dose Sipping technologies, which were licensed from Alza. RingCap is a controlled-release technology, while Dose Sipping involves formulating drugs so they are easier to take for those who have difficulty swallowing, or when they need to take large quantities of drugs.