DewDiligence
10 months ago
MRK sues US over IRA drug-price “negotiation”:
https://www.wsj.com/articles/merck-challenges-u-s-governments-new-powers-to-negotiate-drug-prices-127d4b0c Drugmaker Merck & Co. filed a lawsuit on Tuesday challenging the U.S. government’s plan to negotiate drug prices, saying it is unconstitutional.
Drugmakers were expected to file lawsuits challenging the program, especially as Medicare neared the date later this year when it began naming some drugs it would target for price negotiations.
Among the drugs that analysts expected to face price negotiations are Merck’s top-selling product, the cancer immunotherapy Keytruda.
Merck’s complaint takes issue with the negotiation program’s enforcement rules, which include the power to levy an excise tax of up to 95% of a drug’s U.S. sales if a pharmaceutical company refuses to sell the drug to Medicare patients. Merck said the tax would be coercive and violate the constitution’s Fifth Amendment ban on private property being taken for public use without just compensation. [The so-called “takings” clause.]
Merck also said the law would force companies to agree that the government-mandated prices are “fair,” violating its free speech rights under the First Amendment. For biotech investors, there’s a lot riding on the outcome of this lawsuit and related cases.
Want more details? See https://www.cms.gov/files/document/medicare-drug-price-negotiation-program-initial-guidance.pdf (91 pages).
DewDiligence
1 year ago
Keytruda fails again in prostate cancer—one of the few cancer indications where it has not seen a positive outcome:
https://www.businesswire.com/news/home/20230124006084/en/Merck-Announces-KEYNOTE-991-Trial-Evaluating-KEYTRUDA%C2%AE-pembrolizumab-Plus-Enzalutamide-and-Androgen-Deprivation-Therapy-in-Patients-With-Metastatic-Hormone-Sensitive-Prostate-Cancer-to-Stop-for-Futility Merck…today announced that it will stop the Phase 3 KEYNOTE-991 trial investigating KEYTRUDA…in combination with enzalutamide and androgen deprivation therapy (ADT) for the treatment of patients with metastatic hormone-sensitive prostate cancer (mHSPC).
…At the interim analysis, KEYTRUDA in combination with enzalutamide [Xtandi] and ADT did not demonstrate an improvement in overall survival (OS) or radiographic progression-free survival (rPFS), the trial’s dual primary endpoints, compared to placebo plus enzalutamide and ADT. This is Keytruda’s third recent phase-3 in prostate cancer. In the KEYNOTE-921 trial, which reported results in Aug 2021, Keytruda failed to show a statsig benefit when added to chemo in CRPC (#msg-169574792). In the KEYLINK-010 study, which reported results in Mar 2022, the combination of Keytruda and Lynparza (a PARP inhibitor) failed to show a statisig benefit compared to Xtandi or Zytiga in mCPRC refractory to chemo and either of Xtandi or Zytiga (https://www.clinicaltrials.gov/ct2/show/NCT03834519 ).
Keytruda is a great drug, but it’s not invincible.
DewDiligence
1 year ago
MRK/MRNA cancer vaccine shines in adjuvant melanoma (RFS HR=0.56):
https://www.accesswire.com/731571/Moderna-and-Merck-Announce-mRNA-4157V940-an-Investigational-Personalized-mRNA-Cancer-Vaccine-in-Combination-with-KEYTRUDAR-pembrolizumab-Met-Primary-Efficacy-Endpoint-in-Phase-2b-KEYNOTE-942-Trial …the Phase 2b KEYNOTE-942/mRNA-4157-P201 trial of mRNA-4157/V940, an investigational personalized mRNA cancer vaccine, in combination with KEYTRUDA…demonstrated a statistically significant and clinically meaningful improvement in the primary endpoint of recurrence-free survival (RFS) versus KEYTRUDA alone for the adjuvant treatment of patients with stage III/IV melanoma following complete resection.
Adjuvant treatment with mRNA-4157/V940 in combination with KEYTRUDA reduced the risk of recurrence or death by 44% (HR=0.56 [95% CI, 0.31-1.08]; one-sided p-value=0.0266) compared with KEYTRUDA alone. Note: If this had been a phase-3 trial, it would’ve been considered a failure since the standard cutoff for a one-sided p-value is 0.025. For a phase-2b, however, these results are just fine.
DewDiligence
2 years ago
Lagevrio misses_primary_endpoint_in_large_Oxford_U_trial:
https://ca.finance.yahoo.com/news/merck-ridgeback-biotherapeutics-clinical-non-235000071.html The PANORAMIC study, a UK-based clinical trial sponsored by the University of Oxford, included 25,783 participants who were randomized to open label treatment with LAGEVRIO plus usual care (n=12,821) or usual care alone (n=12,962); mean age of participants was 56.6 years. Primary outcome data were available in 25,000 (97%) participants. Nearly all (>98%) participants were vaccinated, with approximately 95% receiving three or more doses of a SARS-CoV-2 vaccine.
In the preliminary analysis, the primary endpoint of reduction of hospitalizations and deaths within 28 days of randomization, compared to usual care, was not met; 0.8% of patients in both the LAGEVRIO group (n=103/12,516) and the usual care group (n=96/12,484) were hospitalized or died in the first 28 days. Separately, in a retrospective study based on electronic medical records of high-risk patients in Israel, Lagevrio showed a benefit in reducing hospitalizations and death in the patients age 65+ but not in patients age 40-64.
Bottom line: Legevrio (molnupiravir) remains a poor choice for treating COVID. It is being prescribed only when Paxlovid is either unavailable or contra-indicated due to drug-drug interactions (from ritonavir).
DewDiligence
2 years ago
Keytruda narrowly_misses_statsig OS/PFS as_addend_to Lenvina in_ first-line HCC:
https://finance.yahoo.com/news/merck-eisai-present-results-phase-063000955.html
In the final analysis of the trial, there was a trend toward improvement for one of the study’s dual primary endpoints, overall survival (OS), for patients treated with KEYTRUDA plus LENVIMA versus LENVIMA monotherapy; however, the results did not meet statistical significance per the pre-specified statistical plan (HR=0.84 [95% CI: 0.71-1.00]; p=0.0227). The median OS was 21.2 months (95% CI: 19.0-23.6) for KEYTRUDA plus LENVIMA and 19.0 months (95% CI: 17.2-21.7) for LENVIMA monotherapy.
Additionally, treatment with KEYTRUDA plus LENVIMA resulted in a trend toward improvement in the trial’s other dual primary endpoint of progression-free survival (PFS) versus LENVIMA monotherapy; however, the results did not meet the pre-specified threshold at the first interim analysis for statistical significance (HR=0.87 [95% CI: 0.73-1.02]; p=0.0466). These results were presented at ESMO.
DewDiligence
2 years ago
FDA approves MRK’s pneumococcal vaccine, Vaxneuvance for infants/children:
https://finance.yahoo.com/news/u-fda-approves-merck-vaxneuvance-104500312.html
Vaxneuvance was already FDA-approved for adults (#msg-164961310), but I don’t think Vaxneuvance will compete effectively with PFE’s Prevnar-20, which has broader coverage of pneumococcal serotypes and a simpler (one-shot) treatment course (#msg-166441188).
PFE's Prevnar-20 is FDA approved for adults, but is not yet approved for infants/children, so MRK does have a head start in the pediatric market.
MRK pays PFE a royalty of 7.25% on worldwide Vaxneuvance sales during 2022-2026 and a 2.5% royalty during 2027-2035 (#msg-166075692).
DewDiligence
2 years ago
MRK’s V116—(follow-on_to Vaxneuvance)—receives FDA BTD for prevention of pneumococcal disease in adults:
https://finance.yahoo.com/news/merck-announces-u-fda-granted-104500278.html
The phase-3 trial is expected to start during 2022.
V116 is a 21-valent vaccine; the 21 strains are: 3, 6A/C, 7F, 8, 9N, 10A, 11A, 12F, 15A, 15B/C, 16F, 17F, 19A, 20, 22F, 23A, 23B, 24F, 31, 33F, 35B.
Just the facts maam
2 years ago
Thanks DewDiligence. The reason I ask, is that after no trial updates since January 2013, on October 27, 2021, ANIP or an undisclosed partner filed a Clinical Trial Certification/Extension request for their 3,656 patient long-term safety/efficacy Libigel trial. A request to delay submitting results for up to 2 years or 30 days after approval. Though it does not specify if it was a Certification or Extension request, a Certification is usually submitted in relation to filing an NDA.
Certification/Extension Submission
In looking at the study design, the trial was completed on December 2012 (pre-commercialization part of the study). However even the if full trial was completed in August 2016, as listed in the clinical trial history (full safety/efficacy study including post approval observations), there is no obligation to submit results, let alone make request for a delay in submitting results, unless they have or were about to file an NDA.
History of Change Comparison
Then Ms. Elizabeth Powell joined the Rare Disease Business Unit at ANI as Chief Compliance Officer and Head of Legal, Rare Disease in February 2022, assuming responsibility for the Legal and Compliance functions. For the past 24 years, Ms. Powell worked at Merck & Co., Inc., where she was responsible for strategic counsel related to commercial, compliance and FDA regulatory issues, and most recently served as Managing Counsel and Executive Director, U.S. Commercial & Compliance Legal.
Ironically, ANIP advanced their Annual Stockholder meeting from June 2, 2021 to April 27, 2022, which is exactly 6 months after they submitted their Certification/Extension request. It makes me wonder if ANIP or more likely a partner filed an NDA and got a 6-month Priority Review for Libigel.
To date ANIP has never publicly released that Libigel reduced Cardiovascular events in post menopausal women at risk of cardiovascular events by at least 70% (discovered in 2011 or earlier) and they never announced the that it reduced Breast Cancer events by an undisclosed amount (discovered in December 2015 or sooner). Both discoveries are only publicly available in patent applications and related prosecutions.
I realize Merck is facing an LOE for Januvia and Janumet in 2022 (China and EU) and January 2023 (US) and wondered if they are looking to Libigel to offset some of the losses. It would be the first FDA approved female testosterone drug with an instant market in replacing existing off label and compounded testosterone, currently being prescribed.
It appears to fit Merck's criteria for acquisition and partnership
- Fills an unmet need.
- Looking at their R&D and Products page, it appears to fit into at least two of their Areas of Focus, Cardio-metabolic disorders and Oncology.
Areas of Focus
If Merck is interested in female testosterone the Global Consensus Position Statement on the Use of Testosterone Therapy for Women will help in marketing it out of the gate.
The following are some indications that the Position Statement identified as needing more information before making recommendations:
- Cognitive performance, or to delay cognitive decline, in postmenopausal women.
- Impact of testosterone treatment on musculoskeletal tissues
- Prevention of breast cancer (Libigel trial appears to answer this)
- Cardiovascular safety in women at risk (Libigel trial appears to answer this and indicates prevention capbilities).
It creates an R&D roadmap, with the potential of female testosterone eventually becoming a franchise drug with multiple indications.
FYI the patient population from the of the Libigel safety/efficacy trial included postmenopausal women suffering from the following.
- Hypertension
- Dyslipidemia
- Diabetes mellitus
It also included smokers.
It may all be coincidences, but evidence supporting an NDA filing, Ms. Powell coming over ANIP after 24 years with Merck, the Areas of Focus for Merck that Libigel addresses and the Pipeline Page's Key Therapeutic Ares having an empty Women's Health box, left me wondering if as you stated was a clerical error. Or, if Merck and ANIP have entered into a yet to be disclosed partnership.
Keep up the good work DewDilligence.
DewDiligence
2 years ago
Keytruda monotherapy-vs-placebo DFS HR=0.76 in adjuvant* NSCLC, irrespective of PD-L1 status, in phase-3 KEYNOTE-091 trial:
https://www.businesswire.com/news/home/20220317005084/en
Although the DFS endpoint was statig, the effect size was so-so (HR=0.76). The statsig outcome was reported on 1/10/22 (https://www.merck.com/news/mercks-keytruda-pembrolizumab-showed-statistically-significant-improvement-in-disease-free-survival-versus-placebo-as-adjuvant-treatment-for-patients-with-stage-ib-iiia-non-small-cell/ ), but the details were not disclosed until today.
Curiously, in the pre-specified subgroup with PD-L1>=50%, Keytruda’s DFS compared to placebo had a non-statsig HR=0.82—a worse result than in the overall trial.
The HR for OS, a secondary endpoint that is not yet mature, was 0.87.
All told, this is not a great dataset, IMO, but it may be enough for FDA approval. These data may put Keytruda at a competitive disadvantage to Tecentriq and Opdivo in early-stage NSCLC.
*Stage 1b-IIIa.
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