dm+d

Unassigned

New Medicines

AmpligenChronic fatigue syndrome

Information

Ampligen
New molecular entity
AIM ImmunoTech
AIM ImmunoTech

Development and Regulatory status

None
None
Phase III Clinical Trials
Yes
Yes
Mar 21According to its latest 10K form, the company still plans to file in the US. It does not describe plans for EU/UK development [28].
Nov 20AIM ImmunoTech continues to pursue a licence for rintatolimod for the treatment of CFS in the US [26].
Jun 20AIM ImmunoTech has received import clearance from Argentina ´s equivalent to the FDA (ANMAT), to import the first shipment of commercial grade vials of Ampligen to Argentina. The next steps in the commercial launch of Ampligen include ANMAT conducting a final inspection of the product and release tests before granting final approval to begin commercial sales. Once final approval by ANMAT is obtained, GP Pharma will begin distributing Ampligen in Argentina. The FDA requires certain regulations be met with a US manufactured drug not yet approved for commercial use by the FDA, before export to a foreign country after that country ´s commercial approval [27].
Nov 19In its latest quarterly report, AIM ImmunoTech discusses its plans for developing rintatolimod for various cancers but makes no mention of plans for CFS/ME [24].
Sep 19Rintatolimod receives clearance from US FDA under section 802 (b) (2) of the U.S. Federal Food, Drug and Cosmetic Act for exportation to Argentina for treatment of severe CFS [23].
Aug 19Hemispherx Biopharma changes its name to AIM ImmunoTech [23].
Mar 18Has been approved for chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) in Argentina in May 16, but has yet to be launched. Discussions are ongoing withe FDA re a potential US filing [22].
Jan 18Rintatolimod has been available on an Early Access Programme for treatment of CFS in Europe since Jul 16 [19].
Dec 17Hemispherx announces that discussions are ongoing with the US FDA on the next steps regarding a New Drug Application for rintatolimod in ME/CFS [19].
Aug 15Hemispherx Biopharma plan to file for regulatory approval for rintatolimod worldwide, including Europe, Latin America, Australia, New Zealand and the US [19].
Mar 15The company are to seek regulatory approval in Australia and New Zealand [18].
Feb 13FDA does not approve rintatolimod, requesting additional data & another clinical trial. The company plans to appeal [17].
Dec 12The FDA advisory panel voted 8-to-5 against approval, stating that the company hadn’t provided sufficient data [16].
Dec 12The FDA briefing for the arthritis drugs advisory panel meeting has questioned the safety and effectiveness of Ampligen to treat chronic fatigue syndrome [15].
Sep 12The FDA has planned an advisory panel review meeting for the 20 Dec [14].
Aug 12FDA accepts the complete response letter [13].
Aug 12Complete response to FDAs Complete Response Letter filed by Hemispherx. [12]
Jul 12Hemispherx plans to submit the complete response in the 3rd quarter 2012 [11].
Jan 12The FDA has granted an extension for the Company to modify its responses to the Complete Response Letter received Nov 09. The extension will remain open while Hemispherx submits an amended NDA. The company is exploring a new potential companion diagnostic tests for CFS [10].
Dec 10The FDA has granted a 12-month extension for the company to modify its NDA in response to a Complete Response Letter [9].
Dec 09In a complete response letter, the FDA stated that the two primary studies supporting the application did not provide credible evidence of efficacy and recommended at least one additional clinical study which shows a convincing effect and confirms safety in the target population. The FDA also asked the company to resolve outstanding issues at some of its facilities producing Ampligen [7].
May 09FDA review likely to be delayed beyond the end of May 09 (6)
Feb 09Filed in US for CFS in Oct 07 and accepted by FDA for review in Jul 08. Review date originally expected 25/2/09, but this has been extended to 25/5/09 (5).
Feb 09Orphan drug status in US and EU (4)
Jan 09PIII for CFS in US but no development reported in EU (ADIS R&D Mar 07).

Category

RNA synthesis inhibitor that activates an intracellular enzyme (RNase-L) against viral RNA transcripts. It activates toll-like receptor 3 (TLR-3), which is involved in early detection of pathogens and establishment of early defence mechanisms.
ME is not uncommon but the true prevalence is unknown and depends on the criteria used for diagnosis. NICE suggests a prevalence of 4 per 1,000 in the UK [21].
Chronic fatigue syndrome
Intravenous

Trial or other data

Nov 20AIM ImmunoTech announces publication in PLOS ONE of statistically significant data detailing how Ampligen could have a considerable positive impact on people living with the debilitating illness ME/CFS when administered in the early stages of the disease. Analysis of Exercise Treadmill Testing (ETT) data from its PIII trial has identified a subset of patients with at least a two-fold increased exercise response to Ampligen. The ME/CFS population of 208 subjects was divided into two subsets based on symptom duration. The Target subset consisting of 75 patients with ME/CFS symptom duration of 2-8 years was compared to a Non-Target subset consisting of 133 patients with symptom duration outside of the 2-8-year range. Researchers identified 2-8 years as the preferred Target subset for the data analysis in an attempt to reduce possible cases of spontaneous remission after disease onset, while still including several years for ME/CFS symptoms to persist. The placebo-adjusted percentage increase in ETT and the vertical rise in feet while exercising on the treadmill in the Target subset were both at least twice that seen for the combined population of 208 subjects. While no clinically significant ETT response was seen in the Non-Target subset, within the Target subset, 51.2% of the Ampligen-treated subjects improved their exercise duration by at least 25% (p=0.003, a statistically significant value). This magnitude of exercise improvement was associated with additional measures of improved quality of life, including an ability to ascend the equivalent of nearly 175 more vertical feet at Week 40 when compared to the baseline value before the Ampligen treatment was started. The analysis indicates that there may be a relatively short disease duration window early in the course of the disease (before eight years) in which ME/CFS patients may see a significant clinical response. AIM has received approval from the Institutional Review Board to expand its AMP-511 Early Access Program for ME/CFS patients to also include Covid-19 Long Haulers in the clinical sites at Incline Village, Nev. at Lake Tahoe and Charlotte, N.C. The expansion is designed to test the hypothesis that if Ampligen is to have beneficial effects on Long Haulers, then it would likely need to be used earlier in the disease process rather than later [25].
Jul 17PIII AMP-511 study (NCT00215813) is ongoing in the US, but has finished recruitment. It is an open-label study in patients with severely debilitating CFS)/ME. The FDA approved the study for cost recovery. Patients enrolled in the study are responsible for costs related to the therapy, e.g., drug cost, infusion cost, cost of supplies, diagnostic and other laboratory testing. Due to complete Feb 19 [20].
Oct 16Hemispherx Biopharma plans a confirmatory PIII trial in USA [19]
Jul 12The FDA has agreed to accept new analyses of data from the AMP-516 PIII study for review in support of filing. The new analyses may circumvent the need for an additional confirmatory PIII study requested by the FDA in Nov 09. Previous analyses of AMP-516 have included an assessment of cardiovascular risk in Dec 10 (http://jrnlappliedresearch.com/articles/Vol10Iss3/Vol10%20Iss3Stouch.pdf) and, in Mar 12, an analysis showing that the proportions of Ampligen patients with exercise improvements of ≥25% and ≥50% were, respectively, 1.7 and 1.9-fold greater than those patients on placebo. A continuous responder analysis, which examined response improvements from 25% to 50% in 5% increments, showed a greater improvement in exercise tolerance for patients receiving Ampligen vs placebo at every 5% increment above 25% (http://dx.plos.org/10.1371/journal.pone.0031334) . Hemispherx plans to submit the complete response in the 3rd quarter 2012 [11].
Nov 10PIII AMP-516 trial evaluated therapeutic efficacy of rintatolimod to reduce cardiac toxicity in pts with chronic fatigue syndrome. Findings include discussion of sedentary lifestyle produced by extreme fatigue – a significant risk factor for heart disease. A greater proportion of placebo-treated patients had a significant prolongation of the QT interval compared to those who received rintatolimod twice-weekly. The prolonged QT interval in the placebo group was associated with continued use of certain concomitant medications, known to prolong the QT interval and used by CFS patients in an attempt to mitigate symptoms of the disease. In contrast, patients randomized to receive rintatolimod were able to significantly reduce their dependency on these same medications. [8]
Feb 09Ampligen(r) has Emergency (compassionate) Cost Recovery Sales Authorization from the FDA and has a "promising" designation by the Agency on Health Research Quality: "Ampligen(r), an investigational drug that is not approved by the FDA, given intravenously to severely debilitated patients, yielded the most promising results." (5)
Jan 09Available in Canada for ME. New C3 trial in chronic fatigue syndrome due to start May 1998. Also in development for AIDS and cancer. Oral formulation C3. Orphan drug status in US. Filed in EU via centralised procedure for ME Feb 1999. Orphan drug status application made in EU. Filing withdrawn due to economic reasons and is now available on a named patient basis.

Evidence based evaluations