Cometriq Thyroid Approval May Open Door For Use In Prostate Cancer

As cabozantinib wins FDA approval for the rare medullary thyroid cancer, Exelixis stresses its broader development program in other tumor types, notably prostate cancer. The company is likely to submit prostate cancer data to compendia, which if successful could enable reimbursement for the off-label use.

Exelixis Inc.is expected to submit positive trial data for Cometriq (cabozantinib) in prostate cancer to the national drug compendia, a move – following the drug’s approval in rare medullary thyroid cancer – that could enable use and reimbursement in a much larger indication prior to formal clearance.

Cometriq is an oral inhibitor of several kinases including MET, RET and VEGFR2. On Nov. 29, the drug cleared FDA for progressive, metastatic medullary thyroid cancer, a very rare kind of cancer with only 500 to 700 drug-eligible cases in the U.S. per year (Also see "Exelixis Explains Virtues Of Flat Pricing For Cometriq" - Pink Sheet, 30 Nov, 2012.). As the oncology community tends to change practice based upon trial results and compendia listing even ahead of FDA approval, Cometriq’s market introduction means it can be used for whatever purpose a physician prescribes.

And for Exelixis, medullary thyroid cancer as only the beginning, as the company envisages a cabozantinib franchise in multiple tumor types, including much more prevalent diseases like castration-resistant prostate cancer (Also see "Exelixis' Lead-In Trial Design Evaluates Cabozantinib Disease Activity Against Multiple Cancers At 12 Weeks" - Pink Sheet, 6 Jun, 2011.).

The Cometriq approval is an important milestone for Exelixis as the company’s first product to be developed and taken through commercialization, President and CEO Mike Morrissey said during a Nov. 29 analyst call. But the CEO stressed that the clearance for the small indication was a “transitional rather than a transformational event.”

“Our focus remains steadfast on building the broader Cometriq franchise,” Morrissey said.

The drug showed promise in many tumor types in a Phase II study with a novel randomized discontinuation trial design, especially CRPC (Also see "Exelixis Puts '184 Back in Spotlight With "Dramatic" Prostate Cancer Results" - Pink Sheet, 18 Nov, 2010.). The prostate cancer results from the Phase II trial were published in the Journal of Clinical Oncology on Nov. 19.

Exelixis intends to pursue compendia listing for Phase II prostate cancer results.

Asked whether the company would be submitting this publication to the National Comprehensive Cancer Network compendium, Chief Medical Officer Gisela Schwab responded that the company is focused on publishing the considerable amount of data that it has amassed, not only in prostate cancer but also in other indications.

“And we would plan to pursue a compendia listing submission as appropriate when peer-reviewed manuscripts are available. Obviously the decision ultimately is the decision of the review board of the compendia,” said Schwab.

Aside from medullary thyroid cancer, payers and providers will decide how they want to use the drug, Chief Commercial Officer Scott Garland commented.

Flexible Dosing Facilitates Off-Label Use

In medullary thyroid cancer, the drug is indicated for use at a 140 mg daily dose, but in cases of severe adverse reactions, prescribers can adjust down to daily doses of 100 mg and 60 mg.

The company plans to make the product available in late January 2013 at the flat wholesale acquisition cost of $9,900 per 28 days. The flat price applies not just to the different doses that might be used in medullary thyroid cancer, but also to other future indications.

With lower doses approved, it is conceivable that a patient could take a prostate cancer dose of 60 mg, though reimbursement could be challenging and physicians may opt instead to enroll patients in a clinical trial, Credit Suisse analyst Lee Kalowski wrote in a Nov. 30 note.

Two pivotal trials, COMET-1 and COMET-2, are up-and-running for cabozantinib in CRPC. Prostate cancer is the priority but the company is also interested in developing the drug in kidney, liver, breast and lung cancers and is now considering options for pivotal trials in other indications, Morrissey said.

In addition to the company’s own trials, many other studies are in the works as part of a cooperative research and development agreement with the National Cancer Institute’s Therapy Evaluation Program. Per that agreement, established in November 2011, up to 20 clinical trials may be done each year for five years, exploring cabozantinib’s role in a wide variety of cancers. Among other indications, NCI studies are targeting endometrial cancer, non-small-cell lung cancer, renal cell carcinoma, soft tissue sarcomas, uveal melanoma and melamona. Two NCI trials are now recruiting and 11 are in planning stages.

Exelixis has a “robust medical affairs effort,” including a group of medical science liaisons to assist physicians with the medullary thyroid cancer indication as well as with a wider development program, Schwab said.

The company envisages a modest commercial outlay for medullary thyroid cancer, with five outsourced sales reps covering about 80% of target prescribers. The initial commercial investment will provide a foundation to build oncology indications.

“We built everything to ensure we maintained the maximum amount of flexibility and can quickly scale up if additional indications are approved in the future,” Garland said.