Institute For Clinical & Economic Review

In its final analysis of Pfizer Inc. 's widely used drug for transthyroid amyloid cardiomyopathy (ATRCM), the U.S. drug cost regulator called for a reduction of at least 85 percent from its current list price of nearly $268,000 a year to meet generally accepted cost-effectiveness standards. The conclusion, made official in the latest ATRCM report released Monday by the Institute for Clinical and Economic Review (ICER), makes clear that Pfizer's two tafetamines, Vyndaqel and Vyndamax, are subject to the discount requirement. According to ICER's data analysis, in order to meet the cost-effectiveness criteria of between $100,000 and $150,000 per quality-adjusted life year (QALY) or equivalent life year acquired, the annual cost of Tarfamides and the thyrotropin stabilizer category to which it belongs should be adjusted to between $13,600 and $39,000. That means a price cut of between 85 and 95 per cent. The proposed annual cost range is revised up from a preliminary draft report in July. In its response, Pfizer reiterated the challenges and biases it faces in using QALEs as a cost-effectiveness measure for rare diseases, particularly for older patients who have a shorter life expectancy and limited time to benefit from treatment. In addition, the report comes at a time when the FDA is about to make a decision on BridgeBio Pharmaceuticals' competing drug acoramidis, and Alnylam Pharmaceuticals recently submitted an application for its RNA silencer Amvuttra (vutrisiran). This could further affect the competitive landscape of the ATRCM market. It is worth noting that ICER's price assessment covered Tafamidi and acoramidis, but did not include Amvuttra. Although Amvuttra was approved by the FDA for the treatment of ATR polyneuropathy in 2022 and has an annual price tag of $463,500, ICER said there is still not enough data to build an economic model for it. ICER's chief medical officer, Dr. David Rind, noted that the reasons for the price range adjustment include a change in the mortality estimate methodology and the correction of a calculation error in the previous quality of life assessment. At the same time, he highlighted the difficulty in economic evaluation of Amvuttra, especially the lack of data on the prediction of disease change in patients with NYHA Class III heart failure. However, he expects that the information may eventually be made public to meet the requirements of the European health assessment. In the final report, ICER also raised the complexity of comparing the net health benefits of Amvuttra versus stabilizers, noting that the question of the advantages of combination therapy versus monotherapy needs further study. To that end, the group recommends that researchers work to build a comparative profile of the three drugs and stresses the importance of randomized clinical trials to answer this question.

After receiving a complete response letter (CRL) from the FDA on Friday regarding its experimental psychedelic-based treatment, Lykos Therapeutics CEO Amy Emerson said the company will “work tirelessly” to find a path forward for patients with post-traumatic stress disorder (PTSD).The US regulator rejected the use of midomafetamine (MDMA), commonly known as ecstasy, to treat PTSD when used in combination with psychotherapy and has requested Lykos run an additional Phase III study. Emerson said that another trial would take several years to conduct and argued that "many of the requests that had been previously discussed with the FDA and raised at the advisory committee meeting can be addressed with existing data, post-approval requirements or through reference to the scientific literature." The company’s initial submission — which was accepted by the FDA and granted priority review in February — included data from the Phase III MAPP1 and MAPP2 trials, which both met their primary and secondary endpoints demonstrating that MDMA-assisted therapy significantly reduced PTSD symptoms versus placebo.Clinical criticismHowever, Lykos began facing criticism in March when a US drug pricing watchdog issued a draft report claiming that “numerous concerns about the conduct” of the MAPP trials left it unable to assess the net benefit of MDMA-assisted therapy in treating PTSD.According to the Institute for Clinical and Economic Review (ICER), the two studies were “functionally unblinded” given that “nearly all patients” who received MDMA-assisted therapy were able to correctly identify that they were in the experimental arm. Additionally, the organisation asserted that “pressures to have the results of the MAPP trials be favourable” could have influenced clinician and patient reporting.Lykos has refuted those claims, saying it stands behind the design and results of its clinical programme, and a group of clinical investigators, clinicians, supervisors, trainers and monitors who worked on the MAPP trials countered ICER’s arguments in an April opinion piece published in Psychedelic Alpha. Similar concerns were raised during an FDA advisory committee (adcom) in June. Panel members discussed the potential for functional unblinding and expectation bias in Lykos' trials, and also criticised the studies’ design as well as gaps in the dataset. Ultimately, the committee voted against the efficacy and safety of MDMA-assisted therapy for PTSD.  Lykos, however, pushed back against the structure and conduct of the adcom, arguing that there were a “limited number of subject matter experts on the panel,” and that the meeting’s discussions “at times veered beyond the scientific content in the briefing documents.”The adcom had allowed public comments about alleged abuse and misconduct during the MAPPS trials, although Teresa Buracchio, director of the FDA's Office of Neuroscience, said that the agency considered such reports to be “unverified at this point, until we do our own inspections." Next stepsLykos said Friday it will request a meeting with the FDA to ask for the decision to be reconsidered, and to discuss resubmission recommendations.The company, which said it will work to address the agency’s concerns and take advantage of “processes to resolve scientific disagreements,” expects to provide an update on next steps after it meets with the US regulator. “We intend to work tirelessly and use all available regulatory pathways to find a reasonable and expeditious path forward for patients who deserve access to midomafetamine-assisted therapy for PTSD," Emerson commented.

Verona Pharma's Ohtuvayre won FDA approval as a first-in-class COPD therapy three weeks ago. The Institute for Clinical and Economic Review (ICER) has issued an "access and affordability alert" for Verona Pharma’s newly approved Ohtuvayre (ensifentrine), a long-awaited, first-in-class treatment for chronic obstructive pulmonary disease (COPD). Upon its approval from the FDA three weeks ago, Verona revealed that it would charge $2,950 for a monthly dose of the maintenance treatment, which is administered twice daily by a nebulizer. At an annual list price of $35,400, Ohtuvayre costs nearly three times more than the top of ICER’s valuation range for the product. In its final evidence report, ICER calculated a health-benefit price benchmark for Ohtuvayre of $7,500 to $12,700 per year. The Boston-based non-profit suggests fair prices for drugs after analyzing their benefits and risks and gathering input from patients, clinical experts and stakeholders. While ICER recognizes the ability of Ohtuvayre to curb COPD exacerbations and that it is filling an unmet need, there are “uncertainties about how much benefit it may add to unstudied combinations of inhaled treatments,” ICER’s chief medical officer David Rind, M.D., said in a statement. “Unfortunately, the manufacturer chose a price for ensifentrine far above the value-based price,” Rind added. “This may lead payers to implement formulary hurdles that could limit provider and patient access to this promising new treatment.” Verona did not respond immediately to a request for comment. The purpose of an access and affordability alert is to signal that the costs associated with a new service may be difficult for the health care system to absorb, ICER explained. "Manufacturers should set prices that will foster affordability and good access for all patients," ICER said in a release. "For ensifentrine, the manufacturer has priced far above this level and therefore missed an opportunity to provide broad access and increased uptake of the drug." The report comes as the FDA reviews another potentially game-changing COPD treatment, Sanofi and Regeneron’s Dupixent. Two weeks ago, the European Union signed off on Dupixent to be used both in combination with other inhaled treatments and as a solo agent. Evercore ISI has projected that a nod in COPD would boost annual sales of Dupixent by $3.5 billion annually. Meanwhile, Global Data has estimated that Ohtuvayre sales will reach $1.05 billion by 2029. The new treatments could serve a massive population. In the U.S., 8.6 million patients are treated for chronic symptoms of COPD. More than 390 million people worldwide are living with COPD.