FROM BLOOMBERG
The daily pain of millions of Americans, including those threatened by heart attack and stroke, could be about to be relieved thanks to one company’s effective new approach to combining medical treatments.
The U.S. Food and Drug Administration (FDA) has formally approved a new drug, Consensi, designed to simultaneously treat osteoarthritis and hypertension, two common conditions that until now have been treated separately.
The breakthrough has been achieved by Kitov, an Israel-based biopharmaceutical drug development company, which has combined two FDA-approved drugs, celecoxib and amlodipine, in a single pill.
The potential U.S. market for Consensi is vast. Studies indicate that about half of the American population over 65 has osteoarthritis. “The market for pain medications for osteoarthritis is estimated at billions of dollars in annual sales globally,” says Isaac Israel, Kitov’s CEO.
A recent revision of U.S. hypertension guidelines by the American Heart Association and nine other professional health bodies means that many millions of Americans are classified as having high blood pressure. Among all adult Americans about 75 million, (32 percent) have high blood pressure, according to the Centers for Disease Control and Prevention, National Center for Health Statistics.
The overlap between the two groups of patients is considerable. “Of the 50 percent of Americans aged over 50 with osteoarthritis about two-thirds of them have hypertension as measured by the new guidelines,” claims Paul Waymack, Chairman and Chief Medical Officer of Kitov. “We are talking about many millions of patients. It’s a massive market.”
Consensi is a potential game-changer for osteoarthritis patients, who have had limited pain-relieving choices, including narcotics and joint replacement operations. “You can’t replace the joints in half of all Americans aged over 50,” Waymack points out, “and anybody who reads the newspaper knows that we have a major problem with narcotics in the U.S.”
Kitov made the decision to use nonsteroidal anti-inflammatory drugs (NSAIDs) in its product, and chose celecoxib (the active ingredient in Pfizer’s product Celebrex) because of its record of causing fewer gastrointestinal problems than other NSAIDs.
Consensi’s second drug ingredient is the calcium channel blocker amlodipine (a blood pressure-lowering agent that is the active ingredient in Pfizer’s Norvasc).
When Consensi underwent a Phase III trial under an FDA Special Protocol Assessment (SPA) that was completed at the end of 2015, the results were impressive. The effects on patients taking the combination were compared to the effects on control groups taking only celecoxib or only amlodipine. Consensi outperformed amlodipine in reducing blood pressure, beating by 2.5 times the FDA’s requirement, as reflected in the clinical trial protocol to achieve at least 50 percent of amlodipine’s reduction of hypertension.
But what really surprised observers was that during the clinical trial the company unexpectedly saw potential positive effects of the combined drug on the kidneys of patients, whereas celecoxib and other NSAIDs have been associated with decreased renal function and in some cases with renal failure; amlodipine has a positive impact on renal function. “Consensi therapy resulted in a more than 26 percent improvement in renal function over that achieved with amlodipine,” claims Waymack of the Phase III results. “That stunned me and that stunned everybody.”
The findings were so significant that an additional Phase III/IV trial was conducted says Waymack, and it too showed that Consensi more than doubled the beneficial effect of amlodipine by enhancing the reduction of creatinine (the key measurement of renal health) by 102 percent more than that achieved with amlodipine. “We anticipate that the study findings may form a basis for additional future research,” he adds.
Crucially, these results for lowering blood pressure mean that Consensi claims to have labeling that no other NSAID product in the market can match. The approved indication in the product label also notes that, “lowering blood pressure reduces the risk of fatal and nonfatal CV events, primarily strokes and myocardial infarctions.” The company believes that this language is unique in its specificity and will provide it with a major marketing advantage,” says Waymack.
Kitov was founded in 2010 and emerged from a consulting firm established by Waymack, who is a former FDA medical officer, together with an ex-FDA chemist and an ex-FDA pharmacologist. “We got tired of telling companies what to do and they wouldn’t do it,” he recalls. “So we thought we should do things on our own.”
In its Annual Report, the company describes its business model as being “based largely upon the combination of drugs that have not previously been combined ... as well as on new chemical entities that have not yet been administered to humans.” The next investigational compound in Kitov’s pipeline, NT-219, is a molecule intended for use in combination with approved oncology therapies, because it may potentially prevent tumor cells from developing resistance to a number of widely used cancer drugs.
An analyst report on Kitov compiled by H.C. Wainwright & Co. in May, prior to the approval of Consensi by the FDA, reiterated an earlier recommendation to buy rating. The report valued Consensi at $110 million, and took the view that Consensi represented a “relatively low-risk proposition” for investors.
Kitov commissioned a third-party assessment of the U.S. market for Consensi, which included a physician survey of 110 key opinion leaders and high-volume prescribers of Celecoxib in the U.S. Respondents estimated that 40 percent of their osteoarthritis patients currently prescribed celecoxib—and 25 percent of their patients currently prescribed other types of NSAIDs—might potentially be switched to Consensi.
The speed of Consensi’s advancement to FDA approval is partly due to Kitov’s deep understanding of the FDA’s regulatory and clinical trial process. “This was always, in my opinion, low risk as far as getting approval, because everybody on my team had worked at the FDA—my chemists, my pharmacologists and myself,” Waymack says. “As ex-FDAers, we knew what we had to do and what we didn’t have to do. We knew where to go and where not to go, so we saved time and money.”
For the first three years of Kitov’s existence, its experienced staff prepared the ground “to get this positioned exactly where we wanted it within FDA,” Waymack says. The approach paid off, as clinical trials were carried out with 150 patients with only two weeks’ treatment in its Phase III study, while other companies have spent far greater sums on studies that treated patients for a year and involved thousands of patients in each of their Phase III studies, along with Phase I and II studies. In addition, these companies were required to conduct animal studies, which were waived for Kitov.
Because Kitov did not have its own research lab, it originally set out to do “something unique” by combining two drugs to offer osteoarthritis-hypertension treatment, the need for which Waymack identified in the course of his previous work as an academic researcher, surgeon, and consultant.
There are multiple advantages to combining celecoxib and amlodipine in a single pill—some of them incidental. “The biggest problem that doctors have with patients is that they don’t take their medication as it’s prescribed,” says Waymack. “That’s not going to be a good option for someone with hypertension and osteoarthritis, because if you don’t take your blood pressure pill you are [also] not taking your pain pill, and by lunchtime your hip will be informing you that you forgot to do something. We think Consensi may enhance compliance, which is what physicians are forever struggling to achieve with their patients.”
Israel says that this enhanced compliance will be particularly relevant to patients with hypertension. “High blood pressure is known as the ‘silent killer’ due to the absence of noticeable symptoms, so that patients’ adherence to the prescription regimen is low,” he says. “Consensi, therefore, presents a unique value proposition in that it may elevate adherence levels of the antihypertensive drugs to the high levels of adherence of pain medications.”
A single pill also reduces the likelihood that patients will become confused about their medications, and a single prescription halves their liability for copayments to insurance companies.
Crucially, Consensi’s potential for reducing blood pressure and thereby strokes has major implications, because a decline in the incidence of strokes could reduce care costs.
Kitov owns two U.S. patents for Consensi and expects to pursue additional international patent applications for the new drug. Kitov is also looking to distribute beyond the U.S., and has recently secured a licensing agreement for Consensi with a major Chinese pharmaceutical company.
Under the terms of the Chinese agreement, Kitov is entitled to receive an aggregate of up to $3.5 million for FDA approval of Consensi and for satisfying Chinese regulatory requirements; an aggregate of up to $6 million for achieving predefined commercial milestones; and up to 12 percent royalties on net sales. “The total annual NSAID market in China is estimated at hundreds of millions of dollars, according to IMS Health,” says Israel. “Moreover, celecoxib sales in China represent 25 percent of the total NSAID market.”
A separate licensing agreement is in place to distribute Consensi in South Korea, and Kitov is in the process of securing further licensing and distribution agreements in other territories in order to launch the drug globally with a wide network of local partners.
Written by Ian Burrell, for Bloomberg Media Studios
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