Biopharma companies gain significant FDA approvals, while Merck and Lilly release impressive trial results
Editor’s Note: Due to the Thanksgiving holiday, Our Take will return on December 9.
Biopharma companies gain significant FDA approvals, while Merck and Lilly release impressive trial results
Warren, N.J.-based PTC Therapeutics achieved a couple of firsts earlier this month with the FDA’s accelerated approval of a gene therapy to treat an ultra-rare enzyme deficiency.
Not only is the company’s product the first to receive FDA approval for treating the disorder. It’s also the first FDA-approved gene therapy that is administered directly into the brain, the company stated in a news release.
The therapy, eladocagene exuparvovec-tneq, will be marketed as Kebilidi here in the U.S. (It was approved in Europe in 2022, where it’s marketed as Upstaza.)
The fatal disorder it treats is aromatic L-amino acid decarboxylase (AADC) deficiency. AADC is involved in the production of certain neurotransmitters, including dopamine. Those with AADC deficiency experience developmental delays in gross motor function and cognition, as well as weak muscle tone.
AADC deficiency is caused by a mutation in the DDC gene. Kebilidi uses an adeno-associated virus to swap out the mutated gene with one that functions as it should.
Kebilidi is administered in a single surgical session that includes four infusions into the putamen, an area of the brain involved in motor control, the FDA explained in its press announcement of the approval.
Given the rarity of the condition, confirmatory data needed to convert the accelerated approval to a traditional approval will come in the form of long-term follow-up of patients who have already been treated in the study used for the accelerated approval.
Although Kebilidi has only been tested in pediatric patients, the approval covers children and adults across the full spectrum of disease severity. PTC said launch preparations “are well underway.”
The company said it plans to monetize the rare disease priority review voucher the FDA granted for Kebilidi.
Waltham, Mass.-based Syndax Pharmaceuticals also achieved a first — the company’s Revuforj (revumenib) is the first menin inhibitor to receive FDA approval as a treatment for relapsed or refractory acute leukemia with a genetic alteration known as KMT2A translocation.
Syndax noted in a news release that rearrangements of the KMT2A gene “give rise to an aggressive form of acute leukemia that is associated with a very poor prognosis and high relapse rates.” Translocation occurs when part of one chromosome breaks and fuses to a different chromosome, the company explained.
Revuforj is approved for adults and pediatric patients ages 1 year and older. Syndax expects the two highest-strength tablets to be available for order this month. A lower-strength tablet for patients weighing less than 40 kg is expected to be available by next spring; in the meantime, an oral solution will be available through an expanded access program.
Syndax has priced Revuforj at $39,500 per month, FiercePharma reported.
In separate news, an investigational subcutaneous version of Merck’s Keytruda(pembrolizumab) demonstrated noninferiority to intravenous Keytruda based on top-line results from a pivotal Phase III trial of approximately 378 adults with metastatic non-small cell lung cancer (NSCLC).
In the open-label trial, one group of patients received subcutaneous Keytruda together with berahyaluronidase alfa administered as a first-line treatment every six weeks with chemotherapy. The other group received intravenous Keytruda every six weeks with chemotherapy.
Berahyaluronidase alfa is an enzyme used to improve drug absorption and dispersion. The enzyme technology Merck used in developing the injectable version of Keytruda is called Hybrozyme.
“It is very encouraging to see positive Phase III results evaluating this fixed-dose combination of subcutaneous pembrolizumab, which was administered, on average, in approximately 2-3 minutes and has the potential to improve the patient experience as well as increase access for patients and health care providers compared to intravenous administration,” said Dr. Marjorie Green, head of oncology, global clinical development at Merck Research Laboratories. “We plan to discuss these results with regulatory authorities worldwide as soon as possible.”
Merck is evaluating the subcutaneous version of Keytruda versus the intravenous version when administered alone as a first-line treatment for patients with metastatic NSCLC who tumors have high PD-L1 expression, in patients with relapsed or refractory classical Hodgkin lymphoma, and in patients with relapsed or refractory primary mediastinal large B-cell lymphoma.
Keytruda was the world’s top-selling drug based on sales in 2023, growing 19% from the year before to $25 billion, and is projected to be the top-selling drug again this year at an estimated $30 billion in sales.
The intravenous version of Keytruda must be administered at infusion centers and takes approximately 30 minutes. Approved in 41 indications, Keytruda is scheduled to lose patent projection in the U.S. in 2028. An injectable version would help Merck hold on to some of the drug’s market share as biosimilars become available.
Eli Lilly shared impressive trial results last week as well. In a Phase II, placebo-controlled trial, the highest dose of the company’s investigational drug muvalaplin lowered lipoprotein(a) [Lp(a)] levels by as much as 85.8% in adults with elevated levels who had established cardiovascular disease, diabetes, or familial hypercholesterolemia.
Lp(a) is a genetically inherited risk factor for heart disease. Citing the Family Heart Foundation, Lilly stated in a news release that about 20% of people in the U.S., or approximately 63 million individuals, have high levels of Lp(a).
“High levels of Lp(a) have been shown to be a significant risk factor for atherosclerotic cardiovascular disease, affecting over 1 billion adults globally,” said Stephen Nicholls, director of Australia’s Victorian Heart Hospital and Institute and the trial’s lead investigator, adding that current cholesterol-lowering therapies are not approved to lower Lp(a) levels.
“These data represent a needed scientific advancement with the potential to reduce the risk of cardiovascular events such as heart attacks or strokes with a once-daily pill,” Nicholls said.
The trial results were published Nov. 18 in JAMA.
One last bit of pharma-related news from the past week: Novo Nordisk will gradually wind down production of its human insulin pens, Reuters reported. The company did not specify a timeline.
A spokesperson for the company said human insulin would continue to be available in vials.
According to Reuters, most people with diabetes who use insulin and who live in “wealthy nations like the United States” use analog insulin because it permits better blood sugar control. But compared with human insulin, analog insulin is more expensive and more difficult to make.
Instead of producing the human insulin pens, Novo Nordisk will focus on ramping up production of its obesity and diabetes injections, GLP-1 agonists Wegovy and Ozempic (semaglutide).
(Disclosure: Novo Nordisk is a Darwin Research Group client.)
Empowering In-home Care With Private-Duty Nursing, with Jasmine Bhatti
Value-based care has rapidly gained momentum in recent years, but challenges persist — particularly when care is delivered in the home. Our guest, Jasmine Bhatti, Founder and CEO of Navi Nurses, explains how private-duty nursing can deliver better clinical and financial outcomes for providers while offering compassionate at-home care to patients in need. Watch on YouTube here or listen wherever you get your podcasts.
What else you need to know
Caremark Rx, Express Scripts, and Optum Rx filed a lawsuit against the Federal Trade Commission in response to a lawsuit the FTC filed in September against the pharmacy benefit managers and their affiliated group purchasing organizations. The FTC alleged in its complaint the companies engaged in anticompetitive and unfair rebating practices that artificially inflated the list price of insulin products.
In the PBMs’ complaint, which was filed in a Missouri district court, the companies claim the FTC’s administrative process violates their due process rights under the Fifth Amendment, CNBC reported Tuesday. In an administrative complaint like the one the FTC issued in September, the case goes before an administrative judge. Judges’ decisions can be appealed to the FTC’s commissioners, and the commissioners’ final decision can be appealed to a U.S. Court of Appeals.
The insurers’ complaint calls this process “fundamentally unfair” and says allowing the FTC to try the case against the PBMs “would subvert bedrock constitutional principles of accountability and fairness in an attempt to transform significant aspects of an entire industry by regulatory fiat.” An FTC spokesperson wrote in a social media post, “It has become fashionable for corporate giants to argue the FTC is unconstitutional to distract from business practices that we allege, in the case of PBMs, harm sick patients by forcing them to pay huge sums for life-saving medicine.” Healthcare Dive noted that the FTC’s complaint is scheduled for Aug. 27, 2025.
FTC commissioners serve a seven-year term; they are nominated by the president and confirmed by the Senate. No more than three of the five commissioners can be from the same political party. FTC Chair Lina Khan, a Democrat, was sworn in on June 15, 2021. The PBMs have sought to have Khan recused from the case against them, saying she and the other two Democratic commissioners have a history of bias against PBMs. When Commissioner Rebecca Slaughter’s term ends in May, the panel could shift to a Republican majority. The incoming administration is expected to take significant steps toward deregulation, and recent Supreme Court decisions have weakened federal regulators’ authority to interpret the laws they administer.
Amazon One Medical introduced a new Pay-per-visit telehealth service for Prime members that offers low upfront pricing for a clinical visit, treatment plan, and free medication delivery for five health conditions: anti-aging skin care treatment, men’s hair loss, erectile dysfunction (ED), eyelash growth, and motion sickness. Prime members can choose a monthly rate or per-use cost. Customers pay only for the consultation and medication, if prescribed, the company wrote in a blog post, adding that no subscription is necessary other than an Amazon Prime membership.
The new service combines Pay-per-visit (which is the rebranded Amazon Clinic) with Amazon Pharmacy for the five health conditions — which includes free same-day prescription delivery in cities where that service is available. The new offering competes with direct-to-consumer telehealth providers such as Hims & Hers and Ro. Amazon noted in the blog post that Prime members can “save up to 92% on ED treatment versus popular subscription service alternatives.”
Mike Pykosz, who co-founded and served as CEO of Oak Street Health before CVS Health acquired the chain of value-based, senior-focused primary care clinics for $10.6 billion in May 2023, is no longer with CVS Health. According to the announcement of the leadership change, Pykosz informed CVS Health’s top executives earlier in the year of his intentions to leave the company.
What we’re reading
Health systems brace for possible 340B cuts. Becker’s Hospital Review, 11.20.24
AI Can’t Worry About Patients, and a Clinical Ethicist Says That Matters. JAMA, 11.15.24
How Medicare Is Causing Patients To Overpay For Prescription Drugs. Health Affairs, 11.18.24
